Theoretical Population Biology 80 (2011) 80–99

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Theoretical Population Biology
journal homepage: www.elsevier.com/locate/tpb

Generalized population models and the nature of genetic drift
Ricky Der a,b,∗ , Charles L. Epstein a , Joshua B. Plotkin baDepartment of Mathematics, University of Pennsylvania, Philadelphia, United Statesb

Department of Biology, University of Pennsylvania, Philadelphia, United Statesarticleinfo

Article history:
Received 14 September 2010
Available online 28 June 2011
Keywords:
Wright–Fisher model
Cannings modelΛ-Fleming–Viot processΛ-coalescent
Selection amplification
Genetic drift

abstract
The Wright–Fisher model of allele dynamics forms the basis for most theoretical and applied researchin population genetics. Our understanding of genetic drift, and its role in suppressing the deterministic
forces of Darwinian selection has relied on the specific form of sampling inherent to the Wright–Fisher
model and its diffusion limit. Here we introduce and analyze a broad class of forward-time population
models that share the same mean and variance as the Wright–Fisher model, but may otherwise differ.
The proposed class unifies and further generalizes a number of population-genetic processes of recent
interest, including the Λ and Cannings processes. Even though these models all have the same varianceeffective population size, they encode a rich diversity of alternative forms of genetic drift, with significant
consequences for allele dynamics. We characterize in detail the behavior of standard population-genetic
quantities across this family of generalized models. Some quantities, such as heterozygosity, remainunchanged; but others, such as neutral absorption times and fixation probabilities under selection, deviate
by orders of magnitude from the Wright–Fisher model. We show that generalized population models can
produce startling phenomena that differ qualitatively from classical behavior — such as assured fixationof a new mutant despite the presence of genetic drift. We derive the forward-time continuum limits ofthe generalized processes, analogous to Kimura’s diffusion limit of the Wright–Fisher process, and we
discuss their relationships to the Kingman and non-Kingman coalescents. Finally, we demonstrate thatsome non-diffusive, generalized models are more likely, in certain respects, than the Wright–Fisher model
itself, given empirical data from Drosophila populations.
© 2011 Elsevier Inc. All rights reserved.

1. Introduction
Mathematical descriptions of allele dynamics are typically built
upon the Wright–Fisher model (Fisher, 1958; Wright, 1931) or
its diffusion limit (Kimura, 1962; Ewens, 2004). Most theoreticaland applied research rests implicitly on this framework, including Kimura’s work on fixation probabilities (Kimura, 1955), Ewens’
sampling formula (Ewens, 1972; Lessard, 2007), Kingman’s coalescent (Kingman, 1982), tests of neutrality (Hudson et al., 1987;
Tajima, 1989; McDonald and Kreitman, 1991; Fu and Li, 1992; Fay
and Wu, 2000), and techniques for inferring mutation rates andselection pressures (Sawyer and Hartl, 1992; Yang and Bielawski,
2000; Bustamante et al., 2001). Moreover, the development of
the neutral theory of molecular evolution, and our understanding of the role of genetic drift in suppressing the deterministic
forces of Darwinian selection, has relied on the specific form of the
Wright–Fisher model and its diffusion limit.
Kimura’s diffusion is remarkably robust to modifications of
the model’s underlying assumptions. Indeed, many population-

genetic models, including the Moran process (Moran, 1958), anda number of Karlin–Taylor and Cannings processes (Karlin and
McGregor, 1964; Cannings, 1974; Ewens, 2004), share the same
diffusion limit as the Wright–Fisher model (Möhle, 2001). As aresult, Kimura’s diffusion has had an enormous impact on thedevelopment of theoretical and applied population genetics.
Despite its robustness, the Wright–Fisher model (or its
diffusion limit) is not appropriate in all circumstances. The
Wright–Fisher model is founded on a set of assumptions about
how organisms reproduce, and the way in which the constraint offinite-population size enforces dependencies among individuals.
Mathematically, in its simplest form, the process is defined asa time-homogeneous Markov chain describing the evolution of
the frequencies of two neutral, non-mutating alleles. Suppose Xk
denotes the number of type-one individuals in generation k among
a population of fixed size N. Under the Wright–Fisher model thetransition matrix Pij for the probability of j alleles in generationk + 1, given i alleles in generation k is   j 
Pij =∗ Corresponding address: University of Pennsylvania, Lynch Laboratories,
Philadelphia, PA 19104, United States.
E-mail address: rickyder@sas.upenn.edu (R. Der).
0040-5809/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.tpb.2011.06.004

N

i

j

N

1−

i
N

 N −j.

(1)

The specific, binomial form of this transition matrix suggests
an underlying mode of reproduction in which individuals eachR. Der et al. / Theoretical Population Biology 80 (2011) 80–99

produce an extremely large number of gametes, from which
N are then sampled to form the subsequent generation. Thisimplicit mechanism of reproduction provides a good descriptionof some biological organisms, such as semelparous wildflowers,
but, it may not be suitable for all organisms. For example, thereproductive mode of many pelagic organisms (Beckenbach, 1994;
Hedgecock, 1994), including oysters, allows for the possibility thatthe offspring of a single individual may form a substantial fractionof the entire population in a single generation — a possibility ofnegligible probability in the binomial model.
Given the specific mode of reproduction inherent to the
Wright–Fisher model, population geneticists must resolve a fundamental question: how do the predictions and inferences of the
Wright–Fisher model change when its underlying assumptions arerelaxed or generalized to accommodate a larger range of biological situations? Recent developments in coalescent theory (Pitman, 1999; Schweinsberg, 2003; Sagitov, 1999) have uncovered adiversity of biologically relevant models in the backward-timeframework, of which the Wright–Fisher model or, equivalently,
Kingman’s coalescent serves as only a single example. While muchwork remains in exploring the implications and applications ofthese generalized models, the initial task of mathematically classifying such coalescents is mostly complete (Möhle and Sagitov,2001), in the neutral, exchangeable case. In this paper, by contrast, we define and systematically analyze the forward-time population genetics of a large class of models that generalize the
Wright–Fisher model, both with and without selection.
The forward-time equivalents for some non-Kingman coalescents have already been defined and studied, in an abstract
setting. In particular, much is known about the so-called Λand Ξ -Fleming–Viot processes, a class of generalizations of the
Wright–Fisher process, especially concerning the duality between
the forward and backward processes and their relation to various
measure-valued processes (Donnelly and Kurtz, 1999b,a; Birkner
and Blath, 2009). These results have been derived in the very general setting of an infinite type space; nonetheless, even in thesimplest case of two genetic types, there has been no systematic
analysis of the standard forward-time population-genetic quantities for such processes—such as the expected time to fixation of anallele, or the fixation probability of an allele under selection. In thispaper we provide an analytic treatment of such quantities, and weinvestigate how they behave across a broad class of processes thatencompasses the two-type Λ- and Ξ -processes.
The set of models we explore is large, but constrained tomatch the first- and second-order moments of the Wright–Fisher
process (see below). We call this set of models the Generalized
Wright–Fisher (GWF) processes. This broad definition includes theso-called Cannings exchangeable models (Cannings, 1974) as astrict subset. Nevertheless, in contrast to the approach of Cannings,
and more generally any particle-based representation, we specify
the space of GWF models in terms of conditions on the allele
frequency dynamics, without specifying any lineage information.
This change in focus allows us to analyze the properties of Cannings
processes with greater ease than previously possible, even in thepresence of selection. As it turns out, many probabilistic propertiesof Cannings processes are shared by the larger class of GWF models
we study, and indeed they are more easily appreciated in thisbroader context.
Since the first- and second-order moments of a processcompletely define Kimura’s diffusion and determine the varianceeffective population size, one might naively expect that all GWF
processes will have the same continuum limit as the Wright–Fisher
does. This is false. Subtle differences between processes, associatedwith their higher moments, can lead to radically different limiting
behaviors. We will show that some population-genetic quantities(such as the expected absorption time of an allele initiated at81

an intermediate frequency) are robust or even impervious toviolations of the Wright–Fisher assumptions; but other quantities
can differ dramatically from the standard model. When selection is
included, we discover the interesting general fact that most GWF
processes tend to amplify selective effects, relative to the standard
Wright–Fisher model. This amplification leads to some startling
new population-genetic phenomena, including the possibility ofassured fixation for an advantageous allele, despite the presence of
non-trivial random drift. Finally, by comparison to empirical dataon allele frequency dynamics from laboratory populations of fruit
flies, we demonstrate that some of the non-standard population
models we study are equally likely or, in some respects, more likely
than the Wright–Fisher model.
Roughly speaking, by fixing the first and second moments ofa GWF process we are imposing the constraint of neutrality anda choice of time scale on the evolution of the population. Given
these moments, one can imagine two directions of deformation
to the transition probabilities of the process: the third and higher
moments may be increased relative to the second moment, orthey may be decreased. According to classical diffusion theory,
deformations decreasing the higher moments will improve the rateof convergence of the process to the classical Kimura diffusion;qualitatively different results can therefore only occur when thehigher moments are enlargened. This simple intuition will leadto the viewpoint that the Wright–Fisher model, in many of its
properties, is extreme, compared to the set of models with thesame first and second moments.
One of our primary goals in this work is to deepen our
understanding of genetic drift by exploring alternatives to thebinomial drift inherent to the Wright–Fisher model. Although
there has been much work on generalizing other aspects of
population-genetic models, by including demographic variation
or frequency-dependent selection, for example, there has notbeen widespread recognition that the nature of drift itself isconceivably more important than any of these other forces.
Population geneticists typically characterize genetic drift by asingle number – the variance effective population size – whichsimply scales all genetic quantities. As a result, there is widespread
belief among many biologists that there is only a single reasonablemodel of genetic drift. Our analysis of generalized population
processes reveals a rich diversity of alternative forms of genetic
drift, with significant consequences for the dynamics of alleles in
replicating populations.
2. Generalized population processes
The Wright–Fisher model describes the dynamics of twocompeting types in a population of fixed size, N. The model isformulated as a discrete-time Markov chain. Suppose Xk denotes
the number of individuals of type one in generation k. The first two
conditional moments of the Wright–Fisher process satisfy
E [Xk+1 |Xk ] = Xk

(2)

Var[Xk+1 |Xk ] = Xk

1−

Xk
N



.

(3)

Qualitatively, the condition on the mean (2) expresses neutrality,
while the condition on the variance (3) is a gross, second-ordercharacterization of the strength of genetic drift. Drift is strongest
when an allele is at intermediate frequencies.
Cannings (1974) introduced a large family of general population
processes, subsuming the Wright–Fisher model, centered aroundthe concept of exchangeability—a type of invariance under relabeling of individuals. The first two conditional moments of any Cannings process coincide with those of the Wright–Fisher model (2)82

R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

and (3), up to a scaling factor. Viewed in this light, the specific linear and quadratic forms of these moments are natural characteristics of population processes. Taken together, these two conditions
comprise a minimal set of desiderata for any neutral population
process.
Motivated by these considerations, we define a larger class of
population processes: those that coincide with the Wright–Fisher(and Cannings) models in their first two conditional moments.
Definition 1. A pure-drift Generalized Wright–Fisher (GWF) Process
in a population of constant size N is a time-homogeneous Markov
chain, {Xk , k = 1, 2, . . .}, on states {0, . . . , N } whose conditional
moments satisfy
E [Xk+1 |Xk ] = Xk
Var[Xk+1 |Xk ] =

(4)
Nσ

2
N

N −1

Xk (1 − Xk /N )(5)

where σN2 = Var(Xk+1 |{Xk = 1}).
Thus, a GWF process matches the first and second conditional
moments of the Wright–Fisher process, up to a scaling constant,but it might otherwise differ in its higher moments. Loosely
speaking, such processes describe alternative forms of genetic driftthat are roughly similar to the binomial drift encoded by the
Wright–Fisher model.
The scaling constant above, σN2 = Var(Xk+1 |{Xk = 1}), iscalled the (finite-population) offspring variance. In the standard
Wright–Fisher model σN2 = 1 − 1/N. The offspring variance determines the so-called variance effective population size, so that
Ne = N /σN2 . More generally, we call the conditional distribution
Xk+1 |{Xk = 1} the (finite-population) offspring distribution for theprocess.
If we let Q denote the transition matrix of a pure-drift GWF
process, so that Qij = P (Xk+1 = j|Xk = i), then the above moment
conditions are equivalent toN−

jQij = i

(6)

j=0



N
−
i
N σN2
2
i 1−
.
(j − i) Qij =
N −1
N
j=0

(7)

In this notation, the first row Q1,j corresponds to the (finitepopulation) offspring distribution. We will typically consider
sequences of GWF processes Q(N ) , one for each population size
N, just as the Wright–Fisher model prescribes a process for each
population size N.
Since our definition of a GWF process encompasses theCannings models, it includes as special cases the conditional
branching models of Karlin and McGregor (1964) and the sampling
models of Schweinsberg (2003). Unlike those processes, however,an arbitrary GWF process does not prescribe an explicit mechanismof reproduction, such as the exchangeable vector of Cannings or theunconditional offspring distributions of Schweinsberg and KarlinMcGregor. Rather, a GWF process requires simply that, regardlessof the offspring mechanism, the Markov chain describing theresulting dynamics of allele frequency be a martingale and have thesame conditional variance as the Wright–Fisher model. As a result,an arbitrary GWF process does not come equipped, a priori, with an
explicit genealogy – that is, information about which individuals
in generation k share a common parent in generation k − 1 –such as would be required to define a corresponding backwardtime coalescent. Nevertheless, as mentioned above, it is precisely
because we discard genealogical information in the definition of a
GWF process that we will achieve a more tractable forward-time

analysis of standard population genetics quantities – including an
understanding of how these quantities behave among the Cannings
processes.
We should clarify that the offspring variances σN2 associatedwith a sequence of GWF processes, and the limiting offspring variance σ 2 = limN →∞ σN2 , both differ from the variance in offspring
number of an individual, before conditioning, in the Karlin–Taylor
conditional branching process; or from the offspring variance of anindividual, before sampling, in the sampling models of Schweinsberg (2003).
According to diffusion theory (Norman, 1975), a sequence of(N )Markov chains, Xk , indexed by the population size N that eachsatisfy the mean and variance conditions above and for which
σN2 → const as N gets large, can be well approximated by Kimura’s(N )diffusion provided some conditional higher moment E [|Xk+1 /N −
(N )

(N )

Xk /N |2+δ |Xk ] is of order o(1/N ) uniformly. In other words, a
GWF process with small higher moments (relative to its second
moment) can be well approximated by the Wright–Fisher processitself, for large N. We wish to study population models that cannot
necessarily be approximated by the standard model, and so ourdefinition does not impose any constraints on the higher momentsof the process.
In the following sections we analyze the range of behavior forimportant genetic quantities (e.g. absorption times, fixation probabilities etc.) exhibited by Generalized Wright–Fisher processes.
Put another way, we explore the population genetics of alternative forms of genetic drift that are, in their large features, similar to
Wright–Fisher, but which might otherwise depart from the standard model.
2.1. Examples of pure-drift GWF processes
Before analyzing GWF processes in general, we first describe
a few examples of such processes whose behavior illustrates thebroad range of possibilities. Below we use some of these example
processes to illustrate our general results. In order to specify apure-drift GWF process we must define the transition matrix Q(N )and verify that it satisfies the first- and second-moment conditions(6) and (7).
2.1.1. Cannings models
All Cannings models qualify as GWF processes, as remarked
above. Thus, the set of GWF processes contains a large and wellstudied set of models.
We briefly review the definition of Cannings process. Such amodel is based on a random exchangeable vector ν = (ν1 , . . . ,∑νN ) that satisfies the fixed population constraint Ni=1 νi = N.
If individual i contributes νi offspring of its own type to the next
generation, then the number of individuals of a given type, Xk , is a
Markov chain with transition probabilitiesd

Xk+1 |Xk =

Xk
−

νi

i =1
d

where = denotes equality in distribution. The Wright–Fisher
model occurs as a special case when ν is a multinomial distribution.
A simple computation of moments shows that such processes
satisfy (6), (7) and are thus GWF processes.
When a GWF process Xk is generated from an underlying
Cannings process, then the conditional distribution Xk+1 |{Xk = 1}
coincides with the marginal offspring distribution ν1 . Furthermore,
if a GWF process Xk is generated from an underlying Cannings
process then the exchangeable vector ν contains information about
the genealogical properties of a sample, and it can be used to study
a corresponding coalescent (see Discussion).

R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

2.1.2. The Λ1 -modelThis process is in some sense the antipode to the Wright–Fisher
process, and it will serve as a useful, even if biologically unrealistic,
example. The Λ1 -model is a Cannings process defined by thetransition matrix, when i ̸= j:


N −i


 N2 ,
1
Qij = 1 − ,

N


 i

,
2

j=0
j=i

(8)

j = N.
N
At i = 0, i = N the matrix has the standard absorbing states.
Viewed as a Cannings model, the underlying exchangeable
vector ν is specified by the probabilities P (ν = (1, . . . , 1)) =1 − 1/N, P (ν = (N , 0, . . . , 0)) = 1/N 2 , P (ν = (0, N , 0, . . .)) =1/N 2 , . . . , P (ν = (0, . . . , 0, N )) = 1/N 2 . This process describes
a population in which individuals typically produce exactly one
offspring each generation, until a random time (of average length
N generations) at which a single individual replaces the entire
population. We use the nomenclature Λ1 , originating from thetheory of Λ-coalescents (Pitman, 1999), a class of non-standard
coalescents parameterized by measures on [0, 1]. Our discrete
forward-time Λ1 -process corresponds, in the retrospective theory,
to a generalized coalescent with Λ measure concentrated at the
point 1. The Λ1 -Cannings model is unrealistic for most biologicalpopulations, but it will be useful for delimiting certain extreme
aspects of GWF processes.
2.1.3. Eldon–Wakeley models
The Λ1 -Cannings model can be generalized to a process inwhich individuals produce exactly one offspring each generation,
until a random time at which a single individual replaces a fraction
λ of randomly chosen individuals from the entire population. The
value 0 < λ ≤ 1 is a parameter of the model. This generalized
model is also a Cannings process, and its corresponding exchangeable vector ν gives weight 1 − c /N, for some positive value c, tothe partition N = 1 + · · · + 1, and weight c /N to the partition
N = λN + 1 + · · · + 1 + 0 + · · · 0 where the latter equationhas (1 − λ)N ones. Note that λN is required to be an integer forthe (discrete) process. For any σN , there is a unique value c suchthat (5) is satisfied. This value determines how often the population
goes through a ‘‘bottleneck’’—i.e. a jump in allele frequency. These
processes have been proposed by Eldon and Wakeley (2006, 2008,2009) as a model for the population genetics of Pacific oysters. Eldon–Wakeley processes correspond, in the retrospective theory,to Λ-coalescents with Λ measure concentrated at the number λ.
When λ = 1, this process reduces to the Λ1 -model above; the limit
λ → 0 can be shown to converge to the Wright–Fisher model.
To be entirely clear, the Eldon–Wakeley process defined
here is slightly simpler than the definition given by Eldon andWakeley (2006), which included a Moran-like process during thetime intervals between bottleneck events. Nonetheless, the two
definitions have the same continuum limit (see below), provided
the parameter γ in Eldon and Wakeley (2006) is less than two.
2.1.4. Λ-models
The Eldon–Wakeley processes can be generalized to define a
yet larger class of Cannings models. In an Eldon–Wakeley process
the fraction of the population replaced in a bottleneck event is
a fixed deterministic number, λ. We can alternatively assume
that λ is randomly distributed according to some probability
measure Λ on the interval [0, 1]. It can be shown that the resulting
models are also Cannings processes, and, in fact, are the forwardtime analogues of the so-called Λ-coalescents, parameterized bymeasures Λ and studied in Pitman (1999), Sagitov (1999) and83

Donnelly and Kurtz (1999b). We shall refer to these models as Λprocesses, since they are the two-dimensional projections of theΛ-Fleming–Viot measure-valued processes.
2.1.5. Power-law processes
The divide between the Wright–Fisher process and Λ1 -process
can be partly spanned by considering a special, one-parameterfamily that we call the power-law processes. These are defined as
the pure-drift Markov processes whose transition matrices havetails that decay at rate α > 0:


ci

,


α

1
+
b
1
,
i |j − i|


ci
,
Qij =
1 + b2,i |j − i|αδ0,j ,

δ N ,j ,j < i, 0 < i < N
j ≥ i, 0 < i < N

(9)

i=0
i=N

where b1,i , b2,i > 0 are ‘‘slope’’ parameters and the normalization∑N
constant ci is chosen so that j=0 Qij = 1. For any choice of population size N and decay rate α > 0, there exist unique positive
constants b1,i , b2,i , ci which satisfy the GWF conditions ((4) and (5))(Der, 2010).
Unlike the Wright–Fisher model, which exhibits rapid, Gaussian decay in the rows of its transition matrix, the power-law
processes exhibit slower, power-law decay. As a result, we may
informally think of the Wright–Fisher process as a power-law process with α = ∞ (i.e. very rapid decay). In fact, it is possible toprove that the Wright–Fisher model has the same diffusion limit as
the power-law models for any α ≥ 3 (Der, 2010). By contrast, thepower-law models with α < 3 cannot be accurately approximatedby Kimura’s diffusion, and they exhibit behavior that is markedly
different from that of the Wright–Fisher model, as we discuss below. We will call any GWF process, such as the power-law processes with α < 3, for which the standard diffusion approximation
does not hold, a ‘‘non-diffusive’’ population model. There are nevertheless continuum techniques for analyzing the behavior of suchprocesses as N → ∞, described below. In fact, as we discuss below, the continuum limits for the power-law processes 0 < α < 2will turn out to coincide with certain families of Λ-processes.
Fig. 1 shows simulated sample paths from several example GWF
processes, including the Wright–Fisher model, power-law models,
and the Λ1 -model. As the figure illustrates, only the Wright–Fisher
model has continuous sample paths (in its continuum limit), while
the other example processes experience discontinuous changes
in allele frequencies, the sizes of which increase from panels (a)through (d). These paths illustrate the notion that the power-law
models, as α varies from zero to three, span a range of behaviordelineated by the Wright–Fisher model on one side and the Λ1 model on the other.
2.1.6. Convex combinations
Many other GWF processes can be formed by taking mixtures of
two GWF processes. If we have two GWF processes with a common
offspring variance and transition matrices P1 and P2 , then their
combination P = aP1 + (1 − a)P2 , for 0 < a < 1, is also a
GWF process of the same offspring variance, as is clear fromthe linearity of the conditions on first and second moments. The
convexity structure of many classes of GWF processes can be usefulfor deriving their forward-time dynamics in terms of simpler
models. Convex combinations also have the interpretation as arandomization of models; the Λ-processes, for example, can beobtained as the convex hull of the set of Eldon–Wakeley models.
2.2. Incorporating selection and mutation
Our analysis here is concerned with alternative forms of genetic
drift – that is, stochastic effects on allele frequencies arising from

84

R. Der et al. / Theoretical Population Biology 80 (2011) 80–99(a) Wright–Fisher.

(b) Power-law process (α = 2.5).

(c) Power-law process (α = 1.5).

(d) Λ1 process.

Fig. 1. Simulated sample paths for several Generalized Wright–Fisher processes. The Wright–Fisher process has continuous sample paths in its diffusion limit, whereas
non-Wright–Fisherian models experience discontinuous changes in allele frequencies (in their continuum limit). The Wright–Fisher model and the Λ1 -model can been seen
as antipodes, with the power-law processes intermediate, as a function of the frequency and amplitude of their jump sizes.

the finite-population size. It is particularly interesting to ask how
alleles subject to these forms of genetic drift behave in the presenceof natural selection and mutation – a question that is not easily
accommodated using the backward-time genealogical approach(see Wakeley (2009) and Discussion). Selection and mutation are
typically modeled as deterministic forces on the allele frequencies,
and they have a well-accepted mathematical formulation.
We can easily incorporate the standard forms of selection andmutation into the pure-drift processes defined above. Let Q(N ) be
the transition matrix for a pure-drift GWF process. Selection andmutation may be incorporated in a natural way by multiplying
Q(N ) by additional transition matrices denoted S(N ) and M(N )respectively. The model with drift, mutation, and selection is thendefined by the composite transition matrix
P(N ) = S(N ) Q(N ) M(N ) .

(10)

Conceptually, the product above partitions the order of eventsin a generation into three components: (1) alteration of theallele frequency based on differential fitness (i.e. survival until
reproduction) (S); (2) a reproduction stage that includes genetic
drift (Q); and (3) a mutational stage (M).
In order to define the mutation and selection matrices we require only that S(N ) and M(N ) reduce P(N ) to the classical theory ofdeterministic evolution (Haldane, 1932) when the offspring variance equals zero (i.e. when Q(N ) = I), as N → ∞. Mathematically, under the scaling assumption σN2 → const, this amounts torequiring that the transition matrices have generators that converge to the standard convection terms in Kimura’s diffusion:
lim N (S(N ) − I )uN = γ x(1 − x)N →∞lim N (M(N ) − I )uN =

N →∞

1
2

du

(11)

dx

(−θ1 x + θ2 (1 − x))

du
dx

(12)

where the allele of interest has selective advantage γ = Ns,mutation away from class i occurs at rates θi = 2N µi ; u is any
smooth function, and uN is a vector, (u(0), u(1/N ), . . . , u(N −1/N )), sampled from u. It can be shown that the order in which
the matrices are multiplied in (10) is immaterial, as N → ∞.
Appendix A includes a concrete construction of matrices M(N )and S(N ) , which satisfy the conditions above. When Q(N ) is the puredrift Wright–Fisher model, these choices of mutation and selection
matrices produce a model P(N ) that agrees extremely well with thestandard Wright–Fisher model including selection and mutation(Ewens, 2004), even at very low population sizes. It should beemphasized, though, that none of our theoretical results depends
upon the specific form of mutation and selection matrices, but only
on the canonical asymptotic forms (11) and (12).
3. The population genetics of GWF processes
In the following sections we describe the behaviors ofimportant genetic quantities (e.g. absorption times, fixation

R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

probabilities) that are possible under Generalized Wright–Fisher
processes. Aside from providing significant information about the
Wright–Fisher model itself, our analysis uncovers a startlingly
broad span of phenomena for GWF processes—despite the fact thatall GWF processes share the same first- and second-order moments
as the standard model.
In stating our results on absorption times and fixation probabilities, below, we focus on families of GWF processes for which
σN2 → σ 2 < ∞—i.e. the offspring variance remains finite as population size grows. For such models we likewise assume that s= O(1/N ) and µi = O(1/N ). This focus restricts our attention
to models that are more similar to the standard Wright–Fisher
model (for which σN2 → 1) than those exhibiting divergent σN .
Nonetheless, our results on absorption times and fixation probabilities can be readily generalized to accommodate models in which
σN2 diverges with N or shrinks to zero. We elaborate on the relationships between time scaling, diffusiveness, and σN2 at greater length
in the Discussion.
3.1. Time evolution of moments
We start by studying the moments of GWF processes—
including, for example, the heterozygosity. The definition of a puredrift GWF process (4) and (5) implies, by taking expectations, that
EXk+1 = EXk
EXk2+1 =

(13)

Nσ

2
N

N −1

σ

2
N


EXk +

1−

N −1



EXk2 .

(14)

These recurrences can be solved to produce closed-form expressions for the time evolution of the first two moments:
EXk = X0
EXk2

=

(15)

λ + NX0 (1 − λ )X02 kNkN

Var Xk = X0 (N − X0 )(1 − λkN )

(16)
(17)

σ2

where λN = 1 − N −N1 . The behavior of these moments coincides
exactly with those of the Wright–Fisher process. As a fundamental
corollary, any function of the first two moments, including theheterozygosity EXk (N − Xk ), is invariant over the entire set of GWF
processes with a given offspring variance. Moreover, the invarianceof the unconditional moments extends in the presence of non-zero
mutation:
Theorem 1. For any mutation rates θ1 ≥ 0, θ2 ≥ 0, the first two
unconditional moments of any GWF process with σ 2 = 1 − 1/N
coincide, for all time, with the corresponding Wright–Fisher model. In
particular, the first two moments of the equilibrium distribution for a
GWF process converge (as N → ∞) toθ2θ1 + θ2(1 + θ2 )θ2.
E (X∞ /N )2 →(θ1 + θ2 )(1 + θ1 + θ2 )E (X∞ /N ) →

(18)
(19)

The preceding result follows from a simple calculation with themutation matrix M(N ) , which shows that even under mutation EXk
and EXk2 satisfy linear difference equations identical to those of the
Wright–Fisher model.
No such closed system of equations is possible once selection
is present, however, and so the first and second momentsof the stationary distribution of a GWF process with both
mutation and selection may differ from those of the corresponding
Wright–Fisher model. This suggests an interesting interaction
between selection and non-traditional forms of genetic drift—an
idea that we pursue in greater detail below.

85

3.2. Neutral absorption time properties
The time until fixation or loss of a neutral allele is one of
the simplest and most fundamental properties of interest to
population geneticists. Absorption times for the Wright–Fisher
process have long been understood and used to study empirical
populations. For Generalized Wright–Fisher processes, the secondmoment condition (7) implies that 0 and N are the only two
absorbing states, as in the Wright–Fisher process. Moreover,elementary martingale theory implies that the eventual loss
or fixation of an allele is assured. Furthermore, the fixation
probability satisfies the following, classical result:
Theorem 2 (Neutral Probability of Fixation). For a GWF process
without selection or mutation, an allele will fix with probability equal
to its initial frequency.
The mean absorption time of a GWF process may differ fromthat of the standard Wright–Fisher model. We have characterized
the range of mean absorption times that are possible among all
GWF models:Theorem 3 (Absorption Time Bounds). Suppose that σN → σ .
1. For a pure-drift GWF process, the mean absorption time (ingenerations) E τN of an allele initiated at a fixed fraction x of thetotal population size N satisfies (as N → ∞):

−

N

σ2

≤

(x log x + (1 − x) log(1 − x)) ≤ E τNN

σ2log(Nx(1 − x)).

(20)

2. For a pure-drift GWF process, the mean absorption time E τN of anallele initiated at X0 = 1 satisfies (as N → ∞)1

σ2

log N ≤ E τN ≤

N

σ2

.

(21)

The asymptotic bounds described in this theorem are optimalin order N, and they are achieved by specific examples of GWF
models. The proof of this result is sketched in Appendix C, and it
produces stochastic estimates on the distribution of the absorption
time itself. While not pursued here, this approach provides bounds
on all moments of the absorption time, not only the mean.
Note that the Wright–Fisher process meets both of the lower
bounds above, in order N: an allele initiated at a fixed fraction
x of the population will absorb in O(N ) generations, whereas anallele initiated X0 = 1 will absorb in O(log N ) generation. Moreover, we have constructed a GWF process (the ‘‘maximal process’’,described in Appendix B) whose mean absorption time startingfrom a fixed fraction of N achieves the upper bound of N log N
generations. Finally, the Λ1 -Cannings process meets the upperbound, O(N ) generations, for absorption when started at X0 = 1.
Thus, the bounds described by Theorem 3 represent the full rangeof absorption times among GWF models.
Perhaps surprisingly, Theorem 3 shows that the mean absorption time of an allele initiated at intermediate frequencies, e.g.
X0 = N /2, is a fairly stable quantity: this varies over a relatively
narrow range, O(N ) to O(N log N ), over all GWF processes. By contrast, when the initial frequency of a mutant allele is more extreme(near 0 or N), then the absorption time is highly sensitive to theform of genetic drift—and it ranges from O(log N ) to O(N ) generations depending upon the underlying GWF model.
We observed above that the absorption times under the
Wright–Fisher process are very close to the minimum absorption
times achievable under any GWF model; for example, in theclassical process, the absorption times for an allele initiated at X0= N /2 or X0 = 1 are (2 log 2)N and 2 log N, respectively (Ewens,86

R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

2004). This result suggests that the form of genetic drift encodedby the Wright–Fisher model is somewhat unusual compared to
the forms of genetic drift accommodated by the larger class ofgeneralized models—a point we consider in greater detail below.
3.3. Neutral fixation time properties
The conditional fixation time of a neutral allele is also ofinterest to population geneticists. Once again, this quantity is wellunderstood for the Wright–Fisher model, or any other model thatshares the standard Kimura diffusion limit. Here we study the
behavior of the conditional fixation time among the larger familyof GWF processes.
Given a pure-drift GWF process, we consider only those paths
which happen to fix (i.e. absorb at state N). What is the meantime to absorption among such paths, and how does it vary acrossunderlying GWF models? Our next theorem answers this question:
Theorem 4 (Conditional Fixation Time Bounds). Suppose that σN→ σ.

1. Started at a fixed fraction x of the population size N, the mean time
to fixation E τN∗ of a pure-drift GWF process satisfies (as N → ∞)
N

σ2

N

(1 − x) ≤ E τN∗ ≤σ2log(N (1 − x)).

(22)

2. Started at X0 = 1, the mean time to fixation E τN∗ satisfies (asN → ∞)Nσ

2≤ E τN∗ ≤N log N

σ2

.

(23)

The proof is similar to that of Theorem 3. Once again, theasymptotic bounds described by these formulas are tight, with
the Wright–Fisher process behaving near the lower bounds,
whether initiated at a fixed fraction of the population or with asingle individual. Similarly, the ‘‘minimal process’’ (described inAppendix B) meets the upper bounds on mean fixation time.
It is worth commenting that the conditional fixation time
described here is significantly more stable (i.e. does not vary widely
across GWF processes), than the unconditional absorption time,even when the allele frequency starts near the lower boundary.
Explanations for this behavior are deferred to the Discussionsection.
3.4. Absorption times under one-way mutation
If we now suppose that one-way mutation occurs from an alleleof interest to the other allele at rate θ = 2N µ, then eventual loss of
the allele is assured. Using techniques similar to those above, we
can derive bounds on the mean time before loss. For brevity, we
report here a simple, lower bound on the mean absorption time:
Theorem 5 (Time to Loss for One-Way Mutation). Suppose one-way
mutation occurs at rate θ , then
1. Started at a fixed fraction x of the population size, the mean time
to loss E τN of an allele satisfies (as N → ∞)E τN ≥

xN logx(σ 2 +θ/2)



σ2



(θ /2 + σ 2 ) x − σ 2 σ+θ/2
2

.

(24)

2. Started at X0 = 1, the mean time to loss E τN satisfies (as N → ∞)

E τN ≥

log σ 2 σ+θ/2 N2

σ2

For comparison, Kimura’s classical expression for the time toloss of a new mutant with one-way mutation is1
E τN =∫ 1
1/N

y−1 (1 − y)θ−1 dy ∼ 2 log N

where σ 2 = 1. Thus, the time to loss in the Wright–Fisher model isagain close to the lower bound given by our Theorem 5. By contrast,
the mean time until loss of a new allele can be significantly larger ingeneral; the Λ1 -model, for example, has a mean loss time of O(N )generations.
In all the cases presented thus far the Wright–Fisher processabsorbs very quickly, compared to the full range of possible behaviors among all Generalized Wright–Fisher models, particularly
when initiated at allele frequencies near a boundary. These results suggest that the binomial form of genetic drift encoded by
the Wright–Fisher process is much stronger than the drift of mostother GWF processes, despite the fact that the second moments are
the same.
3.5. Probabilities of fixation under selection
We turn now to another classical quantity of interest: theprobability of fixation of an allele under selection. This topic hasreceived relatively little attention in the literature on generalized
population models, because those models are typically studied in
the coalescent framework, which does not easily accommodate
selection (but see Krone and Neuhauser (1997), Neuhauser andKrone (1997), Etheridge and Griffiths (2009), Etheridge et al. (2010)
and Discussion). In the neutral case, all GWF processes have thesame probability of fixation, equal to the allele’s initial frequency.
However, when one allele is selectively favored over the other, weshow that there is enormous variation in fixation probabilities, aswell as some startling phenomena that differ qualitatively fromstandard results in population genetics.
We have derived effective bounds for fixation probabilities
of GWF processes. We have also found specific processes thatattain these bounds; we call them the ‘‘maximal’’ and ‘‘minimal’’processes (see Appendix B). Specifically, we have solved thefollowing extremal problem. Let π (x) be the probability of fixationof an allele initiated at frequency x. For a fixed selection pressure
Ns and offspring variance σ 2 , what GWF process(es) maximize
and minimize π (x) for all x? A priori, it is unclear whether asingle process can be an extremizer for all initializing frequencies.
Remarkably, a solution does exist over the space of GWF processes,
and the computation of their fixation probabilities leads to thefollowing theorem.
Theorem 6. Let γ = σNs2 , and define ( 1 + γ )x,
π− (x) =1 + γx0,x
π+ (x) =γ > −1γ ≤ −11 − γ (1 − x)
1,

,

γ <1
γ ≥ 1.

(26)(27)

Then the probability of fixation π (x) of a GWF process started at allele
frequency x lies between π− and π+ :

π− (x) ≤ π (x) ≤ π+ (x),for all 0 ≤ x ≤ 1.

(28)


.

(25)

1 Note that the first term in the asymptotic expansion for the expected time isindependent of θ .

R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

87

Fig. 2. Probabilities of fixation for Generalized Wright–Fisher processes. The upper and lower bounds for fixation probabilities, which are achieved by the maximal andminimal processes, are shown in dashed. Lighter curves correspond to the Wright–Fisher model, and darker curves correspond to the power-law model with α = 1. The
left panel shows Ns = 0.98, and the right panel Ns = 3.2. Note that when Ns > 1, the power-law process greatly amplifies the fixation probability compared to the
Wright–Fisher model, particularly for an allele introduced at low frequencies. In all cases σ 2 = 1.

Fig. 2 plots the range of fixation probabilities among GWF
processes for a few values of γ , along with the fixation probabilities
for several example processes we have introduced. For every
selection coefficient γ , at least one of the inequalities in (28) is
non-trivial, and in the region −1 < γ < 1 both inequalities are
non-trivial. The maximal and minimal processes, which achieve
the extreme fixation probabilities π+ and π− , are described inAppendix B.
Many insights about the nature of selection and drift ingeneralized populations can be gleaned from Theorem 6, whose
proof is sketched in the Appendix. We divide the discussion ofthese insights into three cases.

contrast, under the Wright–Fisher model fixation is never assured
for any value of s, since limN →∞ π (1/N ) ≈ 1 − exp(−2s) ≈ 2s.
Remarkably, fixation is achieved with probability one in the Λ1 model, despite the presence of stochasticity—i.e. genetic drift withσ 2 = 1. Although the Λ1 -model is an extreme example, similar
phenomena occur in more realistic models, including the powerlaw processes with decay rate α < 2. Fig. 3 compares fixation
probabilities of a new mutant as a function of population size fora number of processes, some of which possess the extraordinary
property of extreme selection amplification. The Wright–Fisher
model does not possess this property because, as we have argued,
the strong form of binomial genetic drift overwhelms the force of
selection even as N → ∞.

3.5.1. Fixation of a new mutant, s fixed
Theorem 6 provides bounds on fixation probabilities when an
allele frequency starts at a fixed fraction of the population size. The
theorem can also be used, heuristically, to derive bounds on the
fixation probability π ∗ of a newly introduced mutant, by inserting
the frequency x = 1/N into (28). For large N, small s > 0, andσ 2 = 1, these amount tos ≤ π ∗ ≤ 1,

s > 0.

(29)

There are a number of interesting consequences of (29).
First among these is the observation that the Wright–Fisher
fixation probability of π ∗ ≈ 2s is very close to the absolute possible
minimum, π ∗ = s. Thus, even relative to the enormous class of
GWF processes, which contains pathological models (the minimal
process in particular), the Wright–Fisher model acts as a vigorous
suppressor of selection. Once again, this supports the idea that theform of genetic drift encoded by the Wright–Fisher model (andthose models with the same diffusion limit) is extremely strong.
In the Wright–Fisher model, drift counteracts the deterministic
force of selection more powerfully than in virtually any othergeneralized population model.
Second, the upper bound on the fixation probability (29)suggests that some processes can tremendously amplify minuteselective differences. The Λ1 -model, in fact, is one such example.
In Appendix D we show that the probability of fixation of anadvantageous allele under Λ1 is

π1 (x) =

1
Ns



x
1−x

1/(Ns) ∫ 1

y−1/(Ns) (1 − y)1/(Ns)−1 dy.

(30)

x

For a fixed value of s > 0, one calculates π ∗ = limN →∞ π (1/N ) =1. In other words, new mutants are assured fixation in the Λ1 model, regardless of the size of s, in the limit as N → ∞. By

Fig. 3. Fixation probability of a new, advantageous mutant for several Generalized
Wright–Fisher processes, as a function of population size N. In all cases s = 0.05
fixed. Note that the power-law processes achieve assured fixation as population
size gets large, whereas the Wright–Fisher process has an asymptotic fixation
probability of approximately 2s.

The limiting fixation probability of a new mutant as the
population becomes large, with s fixed, has been studied by a
few other authors. Lieberman et al. (2005) studied a Moran-likeprocesses in a graph-structured population, and found graphs inwhich π ∗ exceeded the classical value of 2s. In particular, thoseauthors constructed a sequence of graphs (the analogue of N →∞) for which the probability of fixation of a newly introduced typewas assured. Our results indicate that an identical phenomenon

88

R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

can occur even in a well-mixed population, requiring only higherorder modifications to the form of genetic drift.
In the setting of structured populations, processes that suppress
selection also exist, for which fixation probabilities do not differ
from neutrality even in the presence of large fitness differentials(Lieberman et al., 2005). In a well-mixed GWF population, bycontrast, such possibilities are precluded by the lower bounds in
Theorem 6 and (29).

20

15

10

5

3.5.2. Fixation probability from a fixed initial frequency, Ns fixed
The content of Theorem 6 reveals several other striking features
about the nature of selection and drift in GWF populations. In
this section we consider the fixation probability for processes
initialized at a fixed fraction, x, of the total population size.
In particular, we study the behavior of such a mutant as the
population size gets large, with Ns held constant. The standard
diffusion approximation of the Wright–Fisher model indicates
1−exp(−2Nsx)
that such an allele fixes with probability π (x) = 1−exp(−2Ns) .
This expression is strictly less than one (because Ns is finite), sothat such an allele is not guaranteed fixation even in very large
population sizes.
Non-standard models can produce very different behavior.
According to the optimal upper bounds in Theorem 6, π+ (x) → 1
as Ns ↑ σ 2 . Thus an allele starting at any frequency x will beassured fixation in certain continuum GWF models for some finite
value of Ns (as compared to the limit of the previous section, which
required Ns → ∞). Interpreted from the point of view of thediscrete models, there exist GWF processes that produce assured
fixation of advantageous alleles, as the population size increases,
even with Ns constant. An example of this behavior is shown in
Fig. 4.

Fig. 4. Some GWF processes produce the assured fixation of an allele, initially at
any frequency, as N → ∞ with Ns fixed. Here we plot the probability of fixation
as a function of initial frequency for the power-law process with α = 1 (dark) andfor the Wright–Fisher process (light). In both cases σ 2 = 1 and Ns = 5. The curves,from bottom to top, correspond to N = 32, 64, 128, 256, 512, 3200. For the powerlaw process, the fixation probability approaches one, for any initial frequency x, asN gets large; whereas for the Wright–Fisher process, fixation is not assured for any
initial frequency, and the curves converge to function strictly less than 1 as N getslarge.

The maximal process is the ultimate such amplifier of selection
and it features this behavior of assured fixation. But thisphenomena appears in more realistic models as well. In particular,some power-law models exhibit this behavior. For any powerlaw model with α < 2, there exists a critical selective valueγ ∗ < ∞, such that alleles initially at any frequency x with selective
advantage γ , larger than γ ∗ , will assuredly fix, as N → ∞. Whenγ < γ ∗ , fixation probabilities are strictly less than one, as in the

0
0

1

2

3

Fig. 5. Regime of assured fixation in power-law models. Processes with index and1

selection parameters α, γ lying above the curve γ ∗ = (3 − α) 0 (1 − t )−α | log t | dt
experience assured fixation of an allele initially at any frequency x, as N → ∞ with
γ = Ns fixed. Models below the curve have strictly sub-unital fixation probabilities.
For α ≥ 3, the power-law processes are well approximated by the standard Kimura
diffusion, and assured fixation does not occur.

Wright–Fisher model. For the power-law processes with 0 < α <2 this critical value of selection satisfies (see Appendix E):

γ ∗ = (3 − α)

∫ 1(1 − t )−α | log t | dt .

(31)

0

A graph of this expression is shown in Fig. 5. In fact, a more generalformula for the critical selection pressure can be established forthe Λ-processes; we defer that exposition to a future publication.
We note that γ ∗ ranges from 3 to approximately 3.3 in the range
0 < α < 1. In other words, despite the presence of non-trivial
genetic drift in such models, fixation is virtually assured in large
populations, even for only moderately advantageous alleles.
The critical value γ ∗ for assured fixation is an increasing
function of α , the power-law decay rate of the underlying GWF
process. This makes intuitive sense: as α increases, the powerlaw process becomes more similar to the Wright–Fisher model, forwhich fixation is never assured. In fact, for α > 3 the power-law
process has the same diffusion limit as the Wright–Fisher, and soγ ∗ = ∞ in those cases.
The upper bound in Theorem 6 also implies a minimum possible
value for γ ∗ : namely γ ∗ ≥ 1. Thus, whenever Ns ≤ σ 2 , anadvantageous allele always faces some positive probability of loss,
even as N → ∞, in any GWF model. Naturally, this condition
degenerates at σ 2 = 0, in agreement with the well-known
behavior of deterministic evolution without any random genetic
drift.
3.5.3. Fixation of new mutants, Ns fixed
Aside from the exotic phenomena described above, it isalso possible that a GWF population may exhibit a nonzero asymptotic fixation probability for a new mutant, evenwhen Ns is held constant. Under the same assumptions, theWright–Fisher model has an asymptotic fixation probabilityof zero. We do not have an explicit theoretical capability to
predict this behavior, because it would rely on a more detailed
analysis than provided by continuum limits (below). Nevertheless,our numerical investigations (Fig. 6) strongly suggest that thisphenomenon holds for at least those power-law processes with
0 < α < 2. In these cases, whenever γ > γ ∗ there is a positive
probability that a newly arisen mutant will fix, as N → ∞, evenwith Ns fixed. We have not yet identified the general conditions
under which this form of selection amplification occurs.
Lessard and Ladret (2007) have also studied the problem offixation probability under selection for a subset of GWF processes:
the discrete exchangeable Cannings models. In particular, thoseauthors derived an expression for the derivative, with respect toR. Der et al. / Theoretical Population Biology 80 (2011) 80–99

Fig. 6. Probability of fixation of a new mutant, as a function of population size, with
Ns = 5 fixed. The top curve corresponds to the power-law process with α = 1, andthe bottom curve to the Wright–Fisher process. The power-law process amplifies
selection, and it has a strictly positive asymptotic fixation probability ≈ 0.35,
whereas the Wright–Fisher process has an asymptotic fixation probability of zero.
In both cases σ 2 = 1.

selection pressure s, of the fixation probability of a single mutant,under the assumption of weak selection s → 0. By contrast, ourresults are free from the assumption of weak selection and they
provide information about the fixation probability initiated at any
frequency, not only at 1/N.
3.5.4. Deleterious mutations
If a selective strength s < 0 is inserted into Theorem 6, one
discovers an asymptotic upper bound on the fixation probability
π ∗ of a newly introduced deleterious mutant:π∗ ≤1
N 2 |s|.

(32)

This upper bound on the fixation probability is achieved by the Λ1 process.
For finite-population sizes, the quantity above can be larger∗
or smaller than the corresponding classical value πWF≈ (1 −exp(−2|s|)) · exp(−2N |s|) in the Wright–Fisher case, depending
upon |s|. In particular, the fixation probability of a slightly
deleterious new mutation may exceed that of the Wright–Fisher
process. By contrast, when selection is sufficiently strong, theloss of a newly introduced disadvantageous mutant is assured
under some GWF processes, unlike for Wright–Fisher. The sameconsiderations hold for deleterious alleles initiated at a positivefrequency of the population.
4. Continuum theory for GWF processes
Many quantitative questions in population genetics areamenable to diffusion theory, as developed by Kimura andothers. Loosely speaking, the diffusion approximation of the
Wright–Fisher model consists of rescaling the state space and time
domain of the discrete Markov chain, resulting in a continuous
Markov process in the limit N → ∞. Such continuum limits have anumber of attractive properties. It is usually easier to obtain qualitative insight into the continuum process, since models that differ
only in higher-order effects are collapsed onto the same continuum attractor. The space of continuum limits is thus smaller andmore amenable to analysis than the original space of discrete models. In many cases it is possible to obtain closed-form solutions toexit-time problems, such as the absorption times and probabilities
discussed above, which are intractable in the discrete model.

89

A wide range of processes (including, for example, the Moran
process) share the same diffusion limit as the Wright–Fisher model
itself—and they are thus seen as equivalent in most practicalapplications of the theory. In fact, as mentioned above, any
sequence of GWF processes whose offspring variance converges toa constant, i.e. σN2 → σ , can be well approximated by Kimura’s
standard diffusion, provided some conditional higher moment,
E [|Xk+1 /N − Xk /N |2+δ |Xk ], (for any δ > 0) is of order o(1/N ). Thus,
passing to a continuum limit greatly reduces the number of distinct
GWF processes, up to a rescaling of time.
Nonetheless, many GWF processes do not converge to Kimura’s
diffusion. Indeed, we can classify GWF processes by the distinct
continuum limits they attain. The mathematical formalism required to study the continuum limits of GWF processes is more
complicated than that of standard diffusion theory. We have developed the necessary mathematical tools to formulate and productively use continuum limits of GWF processes. While the details of this theory will receive their full exposition in future publications (see also the thesis Der (2010)), it is pertinent here to provide an introduction and outline the essential ingredients of, andinsights gained, from continuum approximations to Generalized
Wright–Fisher processes.
The continuum limit for the Wright–Fisher model, and moregenerally for any GWF model, can be studied via any numberof different state-space scalings. In Kimura’s original approach,allelic numbers are scaled by 1/N, so that the limiting diffusion
is a process on the unit interval [0, 1], which is appropriate for
examining the process when initialized at a fixed fraction, x, ofthe population size. On the other hand, if fluctuations at low
allelic frequencies√ are the object of interest, one might employ, forexample, a 1/ N scaling; here the continuum limit is a process(different from the Kimuran diffusion) on [0, ∞), and√ it can be used
to study the process initiated at some frequency [x N ] (Karlin andTaylor, 1981). In either case, once a state-space scaling has beenchosen, there is typically only a single time scaling, depending on
the asymptotics of the offspring variance σN2 , for which there exists
a non-trivial convergent limit. When σN → σ < ∞, and σ > 0,
this time scaling coincides precisely with the state scaling.
By analogy with the standard diffusion theory of the Wright–
Fisher model, we focus here on continuum approximations of GWF
processes when both time and space are scaled by the population
size N, under the assumption of a convergent offspring variance, i.e.
X (t ) = limN →∞ N1 X[Nt ] , whenever it exists. It is important to note,however, that the assumption σN → σ < ∞ is not essential to thecontinuum theory: divergent σN patterns can be accommodated
simply by changing the time scaling from N to some (for example)
power N α , α ̸= 1. In such cases, the natural scaling regime for theselection pressure s and mutation rates µi must also be modified
to reflect the non-unital exponent of N.
Associated with the convergence of the actual stochastic
processes Xk is the convergence of the generator matrices: P(N ) − I.
Under the scaling assumptions we have made, the existence of acontinuum approximation amounts to asking whether there is anoperator G acting on functions u for which
Gu = lim N (P(N ) − I)uN
N →∞

(33)

where uN is vector of N samples from u. For many sequences of
GWF processes such a generator does indeed exist, and we have
proven the following representation theorem, informally stated
here.
Theorem 7. Let G be a limiting operator as in (33) for a sequence of
GWF Markov chains P(N ) = S(N ) Q(N ) M(N ) with asymptotic offspring

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R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

Table 1
Continuum limits for various GWF processes.
Model

Kernel dΩx (y)Generator Gu(x)Wright–Fisher
Λ1 process
Power-law processes, α ≥ 3

δx (y)xδ0 (y) + (1 − x)δ1 (y)δx (y)1x(1 − x)u′′ (x)2(1 − x)u(0) − u(x) + xu(1)1x(1 − x)u′′ (x)2 1 u(y)−u(x)−u′ (x)(y−x)
x (1 − x ) 0dΩx (y)−x)2 1 u(y)−u((xy)−u′ (x)x(1 − x) 0dy)2
 1 u(y)−(yu−(xx)−u′ (x)(y−x)
x (1 − x ) 0dΩx (y)(y−x)2
1
(
xu
(
x
+
(
1
−
x
)λ)
−
u
(
x
)
+
(1 − x)u(x − λx))
λ21 1(xu(x +(1 − x)λ)− u(x)+(1 − x)u(x −λx)) dΛ(λ)
0 λ2(1 − x)u′ (x) + 1−x x (u(0) − u(x))−xu′ (x) + 1−x x (u(1) − u(x))(3−α) dy(x3−α +(1−x)3−α )|y−x|α−2Power-law processes, 2 < α < 3Cauchy process (α = 2)

1 · dyPower-law processes, 0 < α < 2(3−α) dy−α) dy1(y) + (1−x)(23−α1(y )x2−α |y−x|α−2 [0,x)|y−x|α−2 [x,1](1 − x)δx+(1−x)λ (y) + xδx−λx (y)  x−y   y−x 
xd Λ x1[0,x] (y) + (1 − x)d Λ 1−x 1[x,1] (y)δ0 (y)
δ1 (y)

Eldon–Wakeley processes

Λ-processes
Minimal process
Maximal process

variance σ 2 , selection pressure γ , and mutation rates θ1 , θ2 . Then G
has the form
Gu(x) = γ x(1 − x)u′ (x) ++ σ 2 x(1 − x)

∫ 1
0

1
2

(−θ1 x + θ2 (1 − x))u′ (x)u(y) − u(x) − u′ (x)(y − x)(y − x)2dΩx (y)(34)

for some family of probability measures {Ωx , 0 < x < 1}. Additionally, for any G of the above form, there is a sequence of GWF chains
P(N ) converging to G in the sense of (33).
Theorem 7 establishes that the continuum limit of a GWF
process is characterized by a family of probability measures {Ωx }on (0, 1), typically called a Levy kernel. In this representation Ωx
depends only on the pure-drift matrices Q(N ) , and hence it reflects
the contribution due solely to genetic drift. The decomposition ofP(N ) in (10) is reflected in the limiting generator, G, as a sum of threeterms each encoding separately the effects of selection, mutation,and drift.
The generator G encapsulates all information concerning theforward-time dynamics of a GWF process, and it can be used,
at least in principle, to solve for genetic quantities of interest,
including absorption times, fixation probabilities, stationary distributions, and the evolution of allele densities. The general theoryof continuous-time Markov processes (Dynkin, 1965) provides theconnection between these quantities and solutions to certain operator equations involving G. In this more general theory, the Kolmogorov forward and backward equations read∂µ
= G∗ µ(x, t )∂t∂u= Gu(x, t )
∂t

(35)

where G∗ is the adjoint operator, and they reduce to the standard
diffusion equations only if G is a second-order differential operator.
As an example, the absorption time τ (x) and probability of fixation
π(x), both started at a fixed fraction x of population size, aresolutions toGτ (x) = −1(36)Gπ(x) = 0.

(37)

Besides giving a representation for the generators of GWF
continuum limits, the proof of Theorem 7 also gives a practicalmethod of computing the family of measures Ω in terms of thesequence of pure-drift transition matrices Q(N ) . We have computed
the generators for all of the GWF models discussed above, including
the Wright–Fisher model, the Λ1 -process, the Eldon–Wakeley
processes, the Λ-processes, and the power-law processes. The
generators associated with each of these processes are shown in
Table 1.

As Table 1 suggests, there is a close relationship between
power-law processes and Λ-processes. In particular, a power-law
process with 0 < α ≤ 2 has the same continuum limit as theΛ-process with probability density ddΛλ = (3 − α)λ2−α . In practice,
this implies that the discrete power-law processes can be wellapproximated by the appropriate discrete Λ-models, whichthemselves are examples of Cannings processes. This result also
demonstrates how GWF models constructed purely on the basisof its transition probabilities on the level of allele frequencies
can be sometimes revealed to have a genealogical (i.e. particle)
construction.
Theorem 7 provides a complete and powerful characterizationof the continuum limits that arise from GWF processes. The set ofsuch continuum limits comprise a fairly large space. For example,
Kimura’s classical diffusion model arises only in the extreme caseof a family of delta measures: dΩ (x) = δx (y). Roughly speaking,dΩx (y) has the physical interpretation as a family of ‘‘jump
measures’’, which are propensities for the processes to makediscontinuous changes from an originating state x to another statey. Since only the delta family of measures fails to assign mass tostates other than x, it follows that Kimura’s diffusion is the only
continuum limit of a GWF process (with a given offspring variance)with continuous sample paths. This result is stated in the following
theorem.
Theorem 8. A continuum limit of a GWF process has continuous
sample paths if and only if it is the Kimura diffusion.
Fig. 1 provides visualizations of this theorem. In each of thethree non-Wright–Fisherian processes, the sample paths clearlyshow discontinuities. We elaborate on an intuitive explanation forthis result in the Discussion.
When specialized to the case of a continuum Cannings
process, Theorem 7 provides a formula for the generator which
complements Möhle’s infinite-series representation of a Cannings
generator (Möhle, 2001). Our formula also gives an alternative
representation, in terms of a Levy kernel, for the two-type
Λ-Fleming–Viot process (see Table 1), instead of the usual
Choquet decomposition into Eldon–Wakeley processes. Each ofthese representations may have its advantages, depending on
the application. For example, sample-path properties such as
the continuity Theorem 8 are most easily established using
the representation of Theorem 7. Our results on the fixation
probability under selection required additional representations of
the generator (see Appendix E for an example).
It may be natural to ask which GWF generators, posed in termsof the kernel Ω , are Cannings generators? While we cannot givea complete characterization at the present time, one necessary
condition is that any putative Cannings generator G must map the
space of polynomials to polynomials. From this, it can be seen thatour power-law processes are Cannings if and only if 0 < α ≤ 2.
Equations such as (35)–(37) rarely admit closed-form solutions.
Nonetheless, significant information can be obtained about theR. Der et al. / Theoretical Population Biology 80 (2011) 80–99

nature of solutions without explicitly solving these equations.
Indeed, many of our results on fixation probabilities in thepreceding sections were obtained by an indirect analysis of thesegeneralized Kolmogorov equations (see Appendices C–E).
5. Empirical plausibility of non-diffusive GWF processes
Surprisingly few studies have been concerned with direct
empirical verification of the Wright–Fisher model. Of these, themost extensive and widely cited is the long-term experimentconducted by Peter Buri, a student of Sewall Wright. Buri
maintained 107 independent laboratory populations of Drosophila,
in which he tracked the frequencies of the bw 75 /bw allele overeach of 20 successive generations (Buri, 1956). In each population,
successive generations were initiated with 16 flies, 8 male and8 female, drawn randomly from among the F1 individuals in thepreceding generation, with samples taken every 12 days (Buri’s‘‘Series I’’). The frequency of the bw 75 allele, initiated at 50%
in generation 1, was subsequently recorded in generations 2
through 20 of each population. The time-series of these allele
frequencies may be viewed as 107 independent sample paths ofsome underlying population process.
Buri designed his experiments using the bw 75 allele, which
was presumed to be neutral and non-mutating over the courseof the experiment, to quantify the dynamics of genetic drift andto compare them to the Wright–Fisher model. Buri concluded
that the dynamics observed were largely consistent with neutral
drift, in the sense of Wright–Fisher. In fact, Buri’s data havebecome the standard, textbook example of empirical support for
the Wright–Fisher model of genetic drift (Hartl and Clark, 2006;
Pierce, 2007). Here we revisit Buri’s data and ask if they truly
support the Wright–Fisher model to the exclusion of alternative
forms of genetic drift such as those introduced above.
Buri restricted most of his analysis to the first and second
moments of his empirical time series—that is, the dynamics ofthe mean allele frequency and the heterozygosity. From thesestatistics, Buri concluded that his data conformed to a neutral
Wright–Fisher model, with an effective population size of Ne =18.0 chromosomes. (A variance effective population size Ne is
equivalent to σN2 = N /Ne in the notation above.) However, since
his analysis was based on only the first two moments, whose
dynamics are invariant across GWF models, all GWF models would
be equally compatible with the data from Buri’s perspective. In
order to distinguish among GWF processes, it is necessary toinspect higher moments of Buri’s data or, ideally, the full likelihoodof the data under alternative models.
Genetic data are often presented in the form of allele counts
from a sample of individuals in the population, at one point in time.
In this scenario a coalescent analysis with the Kingman coalescent
as a null model, or the exact coalescent of Fu (2006), would beappropriate. For example, Birkner and Blath (2007) inferred theexponent in the Beta-family of coalescents from empirical datain this manner. Buri’s data, by contrast, comprise a time-series of
the allele frequencies in the entire population, over subsequent
generations. In this case, a coalescent analysis is not appropriate.
Rather, such time-series data enable a more direct and more
powerful likelihood analysis based on the transition matrix of theforward-time population process.
It is easy to compute the likelihood of independent sample
paths drawn from a given Markov chain. Unfortunately, Buri did
not report the actual sample path for each of his 107 populations,but rather only histograms summarizing the states of the(unmarked) populations in each generation. It is computationally
unfeasible to compute the exact likelihood of these histograms, Hk(k = 1, 2, . . . , 20), because of the astronomical number of sets ofsample paths consistent with the histograms. Approximate Monte

91

Carlo methods, including importance sampling techniques, are also
problematic in this case. Nonetheless, for some functionals of thehistograms we can still explore the relative fit of various GWF
models via minimum-norm metrics, such as least squares.
Let dHk be the measure on the set of possible allele frequencies{0, 1/32, . . . , 1} induced by the histogram at generation k. We
consider the following two natural classes of functionals, for p > 0:

∫ 1

mk (p) =|x − 1/2|p dHk (x)(38)

xp (1 − x)p dHk (x).

(39)

0

hk (p) =∫ 1
0

The quantities mk (p) and hk (p) are complementary: mk (p) arehigher-order central moments and thus quantify the monomorphicity of a population, whereas hk (p) are higher-order measuresof heterozygosity. If Q denotes the pure-drift transition matrix
for a given GWF model, then2 H̃k = (Q∗ )k q0 gives the expected
histogram at the kth generation, given the initial state q0 of the
populations. We define the functionals m̃k (p), h̃k (p) relative to H̃ksimilarly to (38), (39), and we consider the minimum Euclidean distance between the data and the expected functionals:
dm =

T
−

|mk (p) − m̃k (p)|2(40)|hk (p) − h̃k (p)|2 .

(41)

k =1

dh =

T
−
k=1

Here T denotes the total number of generations in the experiment,so that T = 20 in Buri’s case. The residuals dm and dh serve as
proxies for the likelihood, quantifying the fit between the empiricalhistograms and the expected model histograms, with respect tomonomorphicity and heterozygosity.
For any given GWF model, there is a one-parameter family ofsimilar models differing only in their variance effective population
size, Ne . Since we are concerned with exploring precisely those
aspects of Buri’s data which lie beyond second-order statistics,
we define the residual of an equivalence class of GWF processes
differing only in Ne as the minimum residual over all possible
variance scalings:
Dm = min dm(42)

Dh = min dh .

(43)

Ne

Ne

We are interested in exploring the fit between Buri’s data andvarious GWF processes. In particular, we consider the power-law
processes, which are characterized by a parameter α > 0 thatquantifies the decay of the transition probability. As discussed
above, the value α = ∞ corresponds precisely to the Wright–
Fisher model, but we have shown that processes with α > 3 havethe same, diffusive continuum limit as the Wright–Fisher model.
Power-law processes with α < 3, by contrast, are non-diffusive
and qualitatively different from Wright–Fisher.
Table 2 shows the values of the residuals Dm and Dh for
the Wright–Fisher process, as well as for the best-fit power-law
process. Generally, the associated minimizing Ne ’s for these models
lie in the range Ne = 16 to Ne = 21, roughly consistent with
Buri’s estimate of Ne = 18 based on the conditional second
moment. For the functionals m(2) and h(1), only second-order
statistics of the data are involved, hence all GWF models achieve

2 ∗ is the adjoint operator.

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R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

Table 2
Residuals for Buri Histogram functionals.
Functional

Parameter p

Wright–Fisher residualBest αBest α residualBest-fit type

Monomorphicity
Monomorphicity
Monomorphicity
Monomorphicity
Heterozygosity
Heterozygosity
Heterozygosity
Heterozygosity

0.5
1
2
3
0.5
1
2
3

8.7 × 10−3
5.9 × 10−3
1.8 × 10−3
4.7 × 10−4
2.7 × 10−2
7.1 × 10−3
4.3 × 10−4
2.5 × 10−5

2.2
1.7

4.8 × 10−3
3.8 × 10−3
1.8 × 10−3
4.7 × 10−4
2.7 × 10−2
7.1 × 10−3
1.8 × 10−4
1.2 × 10−5

Non-diffusive
Non-diffusive
All equivalent
Diffusive
Diffusive
All equivalentNon-diffusive
Non-diffusive

the same fit. As Table 2 shows, in some respects (i.e. the generalized
central moment for p large) Buri’s data are most consistent with the
Wright–Fisher model; whereas in other respects (i.e. other central
moments, and higher-order measures of heterozygosity) they are
more consistent with non-diffusive power-law models.
In addition to the technique summarized in Table 2, wehave also analyzed Buri’s data by inspecting the time-series ofabsorption events (that is, the times at which populations becamemonomorphic). In this case, we can perform an exact likelihood
analysis by computing the probability of the absorption timeseries for any GWF model. For Buri’s data, we find that the bestfit Wright–Fisher model (Ne = 19.8) has a higher likelihood than
any non-diffusive power-law model, but the difference in loglikelihoods (1ll = 0.61) between the Wright–Fisher model andthe diffusive boundary α = 3 is too small to reject one model infavor of the other with a tolerable false positive rate or reasonable
Bayes factor.
Even though Buri’s experiment was designed to test thevalidity of the Wright–Fisher model, and it has long beeninterpreted as having done so, we have seen that the data are
equally, or, in certain features, more consistent with non-diffusivemodels that are fundamentally different than the Wright–Fisher
model. In retrospect, this result is not completely unexpected.
Indeed, Buri’s experiment does not exactly match the conceptual,
Wright–Fisherian mechanism of sampling with replacement;
rather, it is more similar to Schweinsberg’s model of sampling
without replacement (Schweinsberg, 2003). The Schweinsberg
model is known to produce non-Kingman coalescents (and hence
non-diffusive forward processes) when the offspring distribution
is heavy-tailed. It is plausible that in each generation of Buri’s
experiment, some flies, regardless of their genotype, may have
had a disproportionally large number of offspring, perhaps because
they encountered a greater amount of resources, for example. The
resulting heavy-tailed offspring distribution (relative to populationsize) may have resulted in higher-order features that are better
described by non-diffusive processes than by the Wright–Fisher
process.
Our results suggest that neither the standard Wright–Fisher
model nor any single power-law process consistently provides thebest fit to all functionals of Buri’s data. Rather, Buri’s data may
be best explained by some mixture of non-diffusive and diffusive
components.
6. Discussion
We have introduced a broad class of models that describe thedynamics of alleles in a population of constant size. The set ofGeneralized Wright–Fisher models share the same conditional firstand second moments as the standard, Wright–Fisher model, butthey may otherwise differ. We have characterized the behaviorof classical quantities, such as absorption times and fixation
probabilities, across the full range GWF models. Specific examples
of generalized models (e.g. the power-law processes) produce
strikingly different behavior from the classical models—including,

α>0
∞
∞
α>0
0.7
1.1

for example, the assured asymptotic fixation of new mutants, evenintroduced at low frequencies, provided the selective advantage,Ns, exceeds a finite threshold. We have also characterized thecontinuum limits of GWF processes, analogous to Kimura’s
diffusion limit of the Wright–Fisher process. Finally, we havedemonstrated that some of the non-diffusive GWF processes areequally likely, or more likely, than the Wright–Fisher model, given
empirical data on allele frequency dynamics from Drosophila
experiments, which were originally designed to test the validityof the Wright–Fisher model. Taken together, these results compel
us to critically re-assess the widespread reliance on standard,
diffusive models in theoretical and applied population genetics.
Part of our motivation for studying generalized population processes has been to determine which aspects of the Wright–Fisher
model are robust to alternative forms of genetic drift or offspringmechanism—as encoded, for example, by the exchangeable variable ν in a Cannings model. For neutral processes without mutation, many classical quantities of interest remain completely
unchanged by such perturbations: those quantities that are functions solely of the lower-order conditional moments, including fixation probabilities and the first two unconditional moments. These
invariances even hold in the presence of mutation.
Other quantities, however, vary across the set of GWF models.
Neutral absorption times for an allele initiated at intermediate
frequencies and conditional fixation times arbitrarily initiated vary
in a relatively narrow range; whereas absorption and extinction
times of a new mutant vary dramatically. Furthermore, enormous
deviations from the standard model arise in the presence of
selection, regardless of the initial allele frequency, as evidenced byvariation in fixation probabilities over many orders of magnitude.
These phenomena have a unified, intuitive explanation, which
we describe via a thought-experiment. Consider the probability
distribution comprised by a row of the drift matrix, Q(N ) . The
center row of the Wright–Fisher process, for example, is a discrete
symmetric distribution around N /2, approximately Gaussian inshape. We can imagine deforming this probability distribution
while maintaining its mean. Two directions of deformation are
possible: probability mass may be moved to the tails of the
distribution, or further concentrated near the mean. The additional
constraint of a fixed variance (which is enforced by the definition of
the GWF process) implies that for any mass moved to the extremes,
a compensating mass must be concentrated near its center, andconversely. Thus, the two requirements of a GWF process (6)and (7) imply a range of distributions, some with heavier tails
than the Wright–Fisher model, and correspondingly more strongly
peaked about their mean, and some with lighter tails and with lessprobability near their mean. These two directions of deformation
are associated with increases and decreases, respectively, of thehigher central moments of the distribution.
Deforming the Wright–Fisher model by reducing the size ofhigher moments will have virtually no effect on the resulting
behavior, because this only improves the accuracy of Kimura’s
standard diffusion approximation. Hence non-standard behavior
occurs only for deformations that broaden the tails, which requireR. Der et al. / Theoretical Population Biology 80 (2011) 80–99

93

Table 3
Selected bounds and examples.
Genetic quantity

BoundsMean Abs. Time, X0 = N /2
Mean Abs. Time, X0 = 1
Con. Fix. Time, X0 = N /2
Con. Fix. Time, X0 = 1
Asymp. Prob. Fix., X0 = 1

O(N ) to O(N log N )O(log N ) to O(N )O(N ) to O(N log N )O(N ) to O(N log N )s to 1

Asymp. Prob. Fix., X0 = [xN ]Regime of Assured Fixation

π− (x) to π+ (x)1 ≤ Ns ≤ ∞Wright–Fisher model(2 log 2)N2 log N
(2 log 2)N2N

1−exp(−2s)
1−exp −2Ns
1−exp(−2Nsx)
1−exp(−2Ns)≈ 2s

Ns = ∞

Λ1 -model

Power-law models

α<2

α=2

?

?
?
?
?
Ns = ∞ ?

N
N
N
N
1

?
?
1

?
O(N / log N )?
?
?

π 1 (x )Ns = ∞≥xpr
Ns ≥ γ0?
Ns = ∞ ?

≥O(N / log N )

2<α<3
?

≥O(N 3−α )For the definitions of π± , π1 , pr , γ0 , refer to Theorem 6, Eq. (30), Theorem 9 (Appendix E) and Eq. (E.5) respectively. Entries with question marks represent unknown orconjectural properties at the time of writing.

a concomitant concentration of mass near a distribution’s mean.
Fig. 7 illustrates this principle by plotting the center row of thematrix Q(N ) associated with several GWF processes. In each case,the distributions of non-diffusive models are both more strongly
peaked and have heavier tails than the Wright–Fisher model.
Strongly peaked transition distributions, as shown in Fig. 7,
produce longer holding times. That is, the time that an allele
spends at a given frequency before moving to another frequency
is lengthened. The holding time ranges from O(1) generations in
the Wright–Fisher model to O(N ) generations in the Λ1 -model.
This enormous variation accounts, in large part, for the great
sensitivity of the mean absorption time when initialized near anabsorbing state, since such times are dominated by the holding
period in the initial state. Conversely, when started at intermediate
frequencies, initial holding times contribute only a small fraction
to the overall absorption time—which explains why absorption
times are more stable across models when initiated at intermediate
frequencies. This intuition also explains the robustness of theconditional fixation times for new mutants (Theorem 4): despite
initialization near the lower boundary, conditioning on fixation
effectively removes the absorbing state at zero, and once again theinitial holding period contributes negligibly to the overall fixation
time.
What does a lengthy holding time in a neutral model
correspond to in a model with selection? When selection is added,a model with strongly peaked transition distributions, in Q(N ) , willfeature lengthy periods of nearly deterministic, logistic growthof the advantageous allele, in P(N ) . This behavior explains why
non-diffusive GWF processes amplify the effects of selection.
In the Wright–Fisher model, a newly introduced advantageousmutant must reach appreciable frequency quickly (within O(1)generations) in order to escape elimination by drift. In a powerlaw model, by contrast, such a mutant enjoys at least O(N 3−α )generations (for 2 < α < 3) before drift threatens extinction; andthe Λ1 -process provides O(N ) generations of deterministic, logistic
growth. These lengthy periods of nearly deterministic growth fora new mutant serve to amplify the effects of selection, increasing
the chance of fixation compared to the Wright–Fisher model.
The same intuition about the shape of transition distributions
has important implications for the continuum limits of GWF
processes. Some subsets of GWF models converge to Kimura’s
diffusion, whereas others converge to alternative attractors.
Whereas Kimura’s diffusion has continuous sample paths and isparameterized only by the first two moments, all non-standard
GWF continuum limits are non-diffusive—i.e. their sample paths
contain jumps. Thus, non-diffusive GWF models feature two
unusual elements: lengthier holding times that produce periodsof stasis or near-determinism, punctuated occasionally by largechanges in allele frequency arising from the heavy tail.
Biologically, such discontinuities arise whenever a few individuals contribute to an appreciable fraction of the total population in the following generation. This observation has its

Fig. 7. The center row in the transition matrix for various GWF processes. The graphshows the values of Q16,j for j = 0, 1, . . . , N = 30, for the Wright–Fisher model,
power-law model with α = 2, power-law model with α = 1, and Λ1 -model. The
Wright–Fisher model has the lightest tails and it is least centrally peaked, while theΛ1 -process is most centrally peaked with the heaviest tails. Power-law processes
are intermediate.

correlate in the retrospective theory, where the merging of morethan two ancestral lines in a sample becomes possible in nonKingman coalescents. The Λ1 -process is the most extreme in thisrespect, because its sample path begins with a constant allele
frequency and terminates in a violent jump to absorption. Correspondingly, its backward-time version, the Λ1 n-coalescent, consists of n individuals who, after some exponential waiting period,
merge into a single lineage. The power-law processes are intermediate to these (see Fig. 7): as mentioned above, for 0 < α < 2they may be interpreted as Λ models, and thus are mixtures of Eldon–Wakeley models, where the replacement fraction λ is random
and drawn from the probability density dΛ/dλ = (3 − α)λ2−α .
For small α , this density has more mass near one than near zero,
exhibiting behavior similar to the Λ1 -process; as α increases to
α = 3 the behavior approaches the Wright–Fisher model, eventually coinciding with the standard model in the continuum limit.

6.1. The Wright–Fisher process is an extreme model
Table 3 summarizes several bounds we have derived forstandard population-genetic quantities under GWF processes, aswell as the values attained in particular cases. This once again
validates the notion that Wright–Fisher and Λ1 -processes are at
antipodes, with other GWF processes intermediate.
A surprising picture emerges from the results summarized inTable 3: the Wright–Fisher process is the actual- or near-minimizer
for neutral absorption times, and the strongest suppressor of

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R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

selection among all GWF models. In other words, far from being
located in the center of all generalized population processes,
the classical model falls at the extreme of this space. Roughly
speaking, the Wright–Fisher process exhibits the strongest formof genetic drift amongst all models of a given offspring variance.
This accounts for its extremely short absorption times near theboundaries, both with and without mutation, the continuity of its
sample paths, the very short holding time of states, and its strong
suppression of selection.
The extremity of the Wright–Fisher process can be explained
from the point of view of continuum theory and the representation
result of Theorem 7. The Levy kernel associated to Kimura’s
diffusion is a family of delta measures, and hence it is ‘‘pure’’ in thesense that it cannot be written as a non-trivial convex combinationof other kernels; this also implies that its transition matrix likewise
cannot be written as a mixture of two other matrices (in the limit oflarge population size). Thus, the Wright–Fisher process is extreme
in a precise geometrical way: it lies on the boundary of the whole
space of GWF processes. It can be shown that the maximal andminimal processes are also extreme in this sense.
Whereas the generator G for Kimura’s diffusion is a secondorder differential operator, this is not necessarily so for GWF
processes in general. The power-law decay processes, for example,
correspond to generators of fractional order α − 1 (for 0 < α ≤ 3).
When α < 2, this order is smaller than one, meaning that the
selective term of order one dominates the strength of drift in (34).
This provides a mathematical explanation for the phenomenon ofassured fixation that occurs in these models: the strength of drift,
as measured by the order of its generator, becomes weaker thanthe deterministic force of selection.
6.2. Relationship to non-diffusive coalescents
Our present work can, in part, be seen as the construction
and detailed analysis of forward-time analogues of general reproductive models whose backward-time properties have recently
received much attention. As mentioned above, an arbitrary GWF
process contains information only about allele frequencies, and it
does not include any information about parentage as would be required for constructing a coalescent theory. However, GWF processes include the large class of Cannings processes, which comeequipped with an exchangeable offspring distribution and whose
genealogical properties can therefore be studied.
The genealogical properties of Cannings’ processes are morediverse than those of the Wright–Fisher process alone, whose
geneologies are described by Kingman’s classical coalescent in thelimit of large N. In the Kingman coalescent, at most two lineages
can merge at a given point in time. The probabilistic constructionof coalescents that admit multiple (three or more) mergers wasintroduced in Pitman (1999) via the so-called Λ-coalescents. These
processes were recognized by Sagitov (1999) as the continuum
limits, in backward time, of certain discrete Cannings processes.
In addition, Sagitov, Moehle and Schweinsberg classified all thelimiting coalescents that arise from Cannings models, resulting
in the so-called Ξ coalescents that allow simultaneous multiple
mergers. A satisfying and complete duality in the space of Cannings
processes was demonstrated by Möhle (2001), who proved that a
Cannings process converges in forward time to Kimura’s diffusion
if and only if its backward-time genealogies converge to Kingman’s
coalescent.
In Theorem 8, we proved that Kimura’s diffusion is the only
continuum limit of a GWF process that exhibits continuous sample
paths. In conjunction with Moehle’s duality, this establishes anadditional correspondence: the presence of jumps in the allele
frequency of a forward-time Cannings process is equivalent to thepossibility of multiple mergers in its backward-time coalescent.

In fact, these two phenomenon have a common source: theratio of higher moments in the offspring distribution to thesecond moment. This ratio measures the heaviness of the tailsof the offspring distribution; when the ratio is large enough,the forward-time continuum limit is not a diffusion and the
backward-time coalescent features multiple mergers. Biologically,both phenomena are caused by a reproductive mechanism inwhich very large family sizes are occasionally possible.
It is worth emphasizing that the qualitative properties of thecontinuum limit for a Cannings process – that is, whether theforward-time limit is Kimuran or not, and whether the backwardtime limit is Kingman or not – depend on the ratio of its higher
moments to its second moment, rather than on whether σN2
converges or not with large N. The convergence of the offspring
variance determines only the natural time scale under which totake the continuum limit: when σN2 → ∞, the natural time scale
becomes shorter than N generations, and conversely when σN→ 0.
Indeed, each one of our GWF continuum limits, and every generalized Ξ coalescent, can be realized as a limit of discrete processes whose sequence of σN2 behaves arbitrarily, by appropriate
choice of time scale when taking the continuum limit. From thebiological point of view, then, the important quantity in deciding
between the use of a classical model versus a generalized model is
not that of large offspring variances, but rather the relative size ofhigher moments of the offspring distribution to its variance.
Furthermore, we note that the optimal bounds we havederived for the behavior of GWF processes are often achievedby specific Cannings processes. In other words, even though theCannings’ processes are a strict subset of GWF processes, they are
fairly representative of the full range of behavior possible acrossthe broader class of GWF processes. Indeed, many (symmetric)
GWF processes are either Cannings themselves, or they can beclosely approximated by a Cannings process (for example, thecontinuum power-law processes with 0 < α ≤ 2 coincide withthe Λ-Cannings models with an appropriate choice of Λ-measure).
6.2.1. Coming down from infinity
A problem of interest in contemporary coalescent theoryis the question of whether a given generalized (continuum)
coalescent ‘‘comes down from infinity’’—i.e. whether there are
only finitely many blocks in the partition almost surely for all
positive times, when the coalescent is initialized in a partition
with an infinite number of blocks. In particular, it is known
that the Kingman coalescent does come down from infinity,
while the Bolthausen–Sznitman coalescent (corresponding to ourpower-law model α = 2), does not (Schweinsberg, 2000). It is
often presumed that those coalescents that do not come down
cannot form plausible biological models, since this indicatesthat the time to most recent common ancestor for the entire
population of N individuals is infinite (Birkner and Blath, 2009).
The analysis conducted in this paper suggests that this view may
be exaggerated, resulting from a conflation between continuumand discrete models. In a generalized process for which a timereversibility argument is available, the conditional fixation time of
the forward process started at one individual corresponds to thetime to most recent common ancestor for the whole population.
Theorem 4 shows that not only is the former finite in the discrete
process, but has expectation bounded by O(N log N ) for any modelwith asymptotically positive and finite offspring variance. Thissuggests that those coalescents that do not come down frominfinity are simply those whose conditional fixation times scale
faster than the population size N. However, the coalescencetimes could only range between O(N ) and O(N log N )—a relatively
narrow range, in practice, which is unlikely to serve as the basis forquestioning the biological plausibility of a model.

R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

6.3. Fixation of an allele under selection
Our results on the fixation probability of a mutant allele underselection represent a striking departure from what is otherwise
known about fixation probabilities in population-genetic models.
In particular, we have shown that, across a broad range of models,a new mutant introduced even at low frequency may be assured
fixation, asymptotically, despite finite Ns and despite the presenceof non-trivial genetic drift (i.e. despite a finite variance effective
population size). The derivation of these results required anunderstanding of the continuum limits of generalized forwardtime processes.
It may eventually be possible, however, to understand someof these results within a coalescent framework. In general,
coalescent theory cannot easily incorporate selection. The problem
is fundamental to genealogical frameworks, which rely on
characterizing the space of possible genealogical trees before
considering the possibility of mutations at various locations onthese trees. When selection operates, the probabilities of particular
trees cannot be defined independently of the mutations, andthe approach breaks down (Tavare, 2004; Wakeley, 2009). The
ancestral selection graph of Neuhauser and Krone (1997) andKrone and Neuhauser (1997) provides an elegant formal solution
to this problem, but unfortunately it requires extensive numericalcalculations that limit the intuition we can draw (Przeworski
et al., 1999). However, very recent work of Etheridge and Griffiths(2009) and Etheridge et al. (2010) have produced coalescentdual processes in Moran models with selection and continuoustime Moran models with viability selection. When generalized toaccommodate a broader class of underlying population processes,
these techniques may also shed light on the fixation of alleles underselection in generalized population processes.
6.4. Remarks on the neutral theory
Having introduced a large class of generalized population
models, with and without selection, it is useful to reconsider thedevelopment of Kimura’s neutral theory of molecular evolution.
Kimura’s theory emphasized the importance of genetic drift, as
opposed to Darwinian selection, in shaping observed patterns ofgenetic variation within populations and substitutions between
divergent species. However, Kimura’s neutral theory, and much of
the intuition behind it, relied heavily on the specific form of genetic
drift inherent to the Wright–Fisher model and its diffusion limit.
Consideration of the broader class of GWF processes introduced
here suggests that drift is typically much weaker in alternative,plausible models of biological populations. In particular, we havedescribed a large class of biologically reasonable, non-diffusive
processes that contain a relatively weak form of genetic drift andthat exhibit long periods of quasi-determinism. Such models havethe effect of amplifying even minute selective forces. Thus, to theextent that these alternative models are sometimes more accurate
depictions of real populations, our investigation can be seen as
diminishing the role of genetic drift in shaping the fate of mutant
alleles.
Nevertheless, the strongest argument for the neutrality of mostobserved genetic substitutions has centered on the perceived
existence of a ‘‘molecular clock’’—a nearly constant rate of genetic
substitutions observed, per unit of time (in years), across a diverse
range of species with different population sizes (Kimura, 1994).
Generation-time issues aside, this kind of clock-like behavior
would be predicted by the Wright–Fisher model for neutral
sites, because their substitution rate equals the mutation rate,µ, independent of N. By contrast, the corresponding rate of
substitution for selectively advantageous mutants is ≈ 2N µs, a95quantity that is unlikely to remain constant over time or acrossspecies with different population sizes.
These arguments can be re-examined in the context of our moregeneral population models. As with the Wright–Fisher model,
the rate of neutral substitution in any GWF process is simply
N µ N1 = µ. As discussed above, deleterious mutations in GWF
processes may have larger probabilities of survival than in theclassical scenario, but only marginally so, and certainly fix with
rates that are orders of magnitude lower than the neutral rateµ. If novel, advantageous mutations with fitness advantage s fix
with probability π (N , s) under some GWF model, then the rate ofsuch substitutions is then N µπ (N , s). If this quantity is to remain
constant, independent of population size, we must assume π =g /N, for g with no functional dependence on N. But the lower
bound in (29) reads π ≥ s, or g ≥ Ns, which contradicts theindependence of g on N. Thus, the theory of generalized processes
would only further support the hypothesis of pre-dominantly
neutral or near-neutral evolution, at least to the extent that themolecular clock exists and is independent of population size andspecies (but see Li (1993)).
6.5. Implications for the inference of selection and mutation
Population geneticists often infer selection pressures andmutation rates from sampled genetic data by comparison to thesteady state distribution of allele frequencies under mutation,
selection, and drift. Such comparison typically assumes an infinite
number of unlinked loci (Sawyer and Hartl, 1992; Bustamante
et al., 2001; Desai and Plotkin, 2008), and may utilize the Poisson
Random Field approximation. We have developed an analogous
theory of steady state distributions for GWF processes, and its
application to inference techniques will be described elsewhere.
Nonetheless, a few qualitative insights about inference are
implied already in the present work. We have seen that the
Wright–Fisher model is extreme in the sense that, amongst alarge class of population processes, it tends to minimize selective
differences among alleles due to the powerful nature of its
genetic drift. Correspondingly, if the underlying drift process
is not necessarily Wright–Fisherian, then estimates obtained
under a Wright–Fisher assumption are expected to produce only
upper bounds on the true strength of selection. Any particularpattern of data suggesting the presence of strong selection, under
Wright–Fisher, could conceivably be explained by a smaller valueof s and a weaker, alternative form of drift. Therefore, one expects
that replacing Wright–Fisherian drift with other types of GWF
drift will have the consequence of moving estimated selection
values closer to zero. This further suggests that under all nonWright–Fisher models, a greater standard of evidence would be
required to reject the null assumption of neutrality.
Acknowledgments
We thank Warren Ewens for many detailed and encouraging
discussions, as well as insightful input throughout the course ofthis research. The authors also recognize the close reading of
the manuscript by two anonymous reviewers, and their valuablecommentary which improved the manuscript. JBP acknowledges
funding from the Burroughs Wellcome Fund, the David and Lucile
Packard Foundation, the James S. McDonnell Foundation, and theAlfred P. Sloan Foundation. RD, CLE, and JBP also acknowledge
support from the Defense Advanced Research Projects Agency(HR0011-05-1-0057 and HR0011-09-1-0055).

96

R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

Appendix A. Mutation and selection matrices

Appendix C. Proofs of theorems

The mutation matrix M(N ) can be specified as follows: after
reproduction, each individual mutates to the opposing typeindependently with respective probabilities µ1 , µ2 . If we define
Mjk as the probability that, starting with j individuals of type A,
one obtains k individuals of type A after mutation, then Mjk is
distributed according to a sum of independent binomial randomvariables Xj and Yj :P (Xj = r ) =P (Yj = r ) =

 
j

r



j −r
1

(A.1)

µr2 (1 − µ2 )N −j−r

(A.2)

(1 − µ1 )r µ

N −j



r

Mjk = P (Xj + Yj = k).

(A.3)

The selection matrix S(N ) can be chosen with the property
that its ith row is a binomial distribution supported on states{i, . . . , N }, and a probability parameter such that the mean ofthe distribution coincides with the standard selected binomial
Wright–Fisher model of parameter s. It is simple to see, by Taylor
expansion, that the preceding choices for M and S satisfy theconstraint (11) and (12).

0
(1)
x2
0

0

···

 .
 ..

0
0

0


···

0
(2)
x3

···

0

(B.1)




0

N −i

(i)

x3 =

i

N (i + 1)
N −i
N −i

N

,

−

N

X0 (N − X0 )α k (2 − α k )P (τ > k) ≥(N − α k (N − X0 ))(N − X0 α k )
X0 (N − X0 ) kαP (τ > k) ≤ min 1,
N −1

x2 =

N (i + 1)

0
(1)
x2
(2)
x1
0

 x1

 0

 0

 ..
.

0
0
(2)
x2
(3)
x1

,
(B.2)

.

EY 2

EY 2

Var (Xk )Var (Xk ) + (N − X0 )2

0
0

0

···

(B.3)






···

0

0

Var (Xk )Var (Xk ) + X02

(i)

(i)

x3 =

i
N

−

i
N (N − i + 1)
i

.

,

1

(i)

x2 = 1 −.

(C.6)

P (τ > k) ≥X02 (N −X0 )2 −[Var (Xk )]2(X02 +Var (Xk ))((N −X0 )2 +Var (Xk ))

,

(C.7)

which is algebraically equivalent to (C.1).
For the upper bound, Markov’s inequality implies that if |Y | ≤K , 0 ≤ λ < K , thenwith entries
x1 =

(C.5)

Inserting this into (C.3), and substituting the moment formulas (15)and (16), gives

0 
(1)
x3 
(2) 
x3 

···

.

(C.4)

From the Cauchy–Schwarz inequality applied to Xk 1Xk >0 thesecond term of (C.3) satisfies:
P (Xk = 0) ≤

···
···

(C.3)

.
+ λ2
Putting Y = Xk − X0 and λ = N − X0 , one determines
P (Y ≥ λ) ≤Define Q as the transition matrix:
(1)

(C.2)

Proof. We start with the lower bound, beginning with:

+

 1

(C.1)

where α = 1 − N1 .

P (Xk = N ) ≤
(i)

(i)

Lemma 1. For a Generalized Process Xk , started at X0 , and with σN2 =1 − 1/N, we have the estimates for the absorption time τ :1whose entries arex1 =We begin by proving the lemma:

The first term can be estimated by the Glivenko–Chebyshev
inequality: if Y is a random variable of mean zero, and λ > 0,



···

0
(1)
x3
(2)
x2

C.2. Theorem 3= P (Xk = N ) + P (Xk = 0).

We define Q− as the pure-drift transition matrix:1
x(1) 1(2)
x 1This is a consequence of the martingale property of neutral
processes without mutation, and is immediate from the stoppingtime theorem.

P (τ ≤ k) = P (Xk = N ∪ Xk = 0)

Appendix B. The minimal and maximal GWF processes

C.1. Theorem 2iN

P (|Y | ≤ λ) ≤

,
(B.4)

N (N − i + 1)
We refer to the GWF processes induced by the transitions
Q± as the maximal and minimal processes, respectively. They
play an important technical role in our continuum theory, by
delimiting two extreme boundaries. For example, the proof sketch
to Theorem 6 below shows that these two models minimize
and maximize the mean, and thus the fixation probability,
given an initial allele frequency, across all GWF processes withselection; they operate as the ultimate selection amplifiers andsuppressors. Additionally, it can be demonstrated that their neutral
absorption time is O(N log N ), and thus achieve the upper bounds
in Theorems 3 and 4.

K 2 − EY 2
K 2 − λ2.

(C.8)

Since Yk = Xk − N /2 is bounded by K = N /2, we have
P (|Xk − N /2| ≤ λ) ≤=N 2 /4 − E (Xk − N /2)2
N 2 /4 − λ2

−EXk2 + N · EXk.
N 2 /4 − λ2

(C.9)

Inserting λ = N /2 − 1, and applying the recurrence solutions (15)and (16), one obtains the desired outcome:P (τ > k) = P (|Xk − N /2| ≤ N /2 − 1)≤

X0 (N − X0 )N −1

αk . 

(C.10)

R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

By summing over the estimates (C.1), (C.2), and evaluating
the asymptotics of the resulting expressions, one finds the mean
absorption time bounds described in Theorem 3.

97

C.4. Theorem 5
Let one-way mutation occur at rate µ > 0. A computation withthe mutation matrix of (A.3) shows
E (Xk+1 |Xk ) = Xk (1 − µ)C.3. Theorem 4

E (Xk2+1 |Xk ) = cXk +1−∗

The Markov chain Xk conditioned on ultimate fixation, defined on
the state space {1, . . . , N } has the transition matrix:Q∗ij = Qijj(C.11)

i

σ

2



N −1

(1 − µ)2 Xk2(C.21)

where c = µ + N σ 2 /(N − 1) · (1 − 2µ). Taking the expectation of both sides, the lower moments satisfy the following
recurrences:
EXk+1 = v EXk(C.22)∗

where Qij is the unconditioned transition. X has a single absorbing
state at N; let τ ∗ be the time to fixation, when started at X0∗ . We first
demonstrate the following estimates on the distribution of τ ∗ :(C.20)



EXk2+1 = cEXk + v 2


1−

σ
EXk2
N −1
2
N



(C.23)

where v = 1 − µ. Solving the recurrences produces

Lemma 2.

EXk = v k X0

(C.24)N − X0v k−1 X0
(1 − (vλN )k ) + (v 2 λN )k X02
EXk2 = c
1 − vλN(C.25)N −1
α k ≤ P (τ ∗ > k) ≤ min 1, (N − X0∗ )α k

(C.12)

σ2with λN = 1 − N −N1 . Using the Cauchy–Schwarz inequality, one
finds

where α = 1 − 1/N.
Proof. From (C.11) we derive the conditional mean relation:

−
j

1
1− 2
jQ∗ij =j Qij = (i(1 − i/N ) + i2 ) = 1 + α ii jiEXk∗+1 = 1 + α EXk∗

(C.14)

whose solution is
EXk∗ =1−α

1−αP (τ > k) ≥

EXk2

.

(C.26)(EXk )2
EXk2=

v k X0C (1 − (vλN )k ) + X0 (vλN )k(C.27)v
where C = 1c−vλ. The preceding expression has the lower bound−1

N

X0 (vλN )x∫ ∞0

C (1 − (vλN )x ) + (vλN )x X0dx =X0 (log(X0 /C )).
−[log(vλN )](X0 − C )For large N, this bound reads+ α k X0∗ .

(C.15)Eτ ≥∗Applying Markov’s inequality on the positive process Xk − 1, one
derivesP (τ ∗ ≤ k) = P (Xk∗ = N ) ≤EXk∗ − 1
N −1

N − X0∗N −1(C.28)

where k = θ /2σ+σ 2 . This in turn reduces to the asymptotic expres2(C.16)
C.5. Theorem 6.

(C.17)To discover an upper bound, apply Markov’s inequality on thepositive process N − Xk∗ :P (N − Xk∗ ≥ 1) ≤ N − EXk∗

(C.18)

so thatP (τ ∗ > k) = 1 − P (Xk∗ > N − 1) = P (Xk∗ ≤ N − 1)

≤ N − EXk∗ = α k (N − X0∗ )which implies the upper bound of the theorem.

NX0 log(X0 /(kN ))(θ /2 + σ 2 )(X0 − kN )sions in Theorem 5, in the special cases X0 = 1 and X0 = [xN ].

.

Finally, after substituting the recurrence solution (C.15) and taking
complements, find the lower boundP (τ > k) ≥ α k

EXk2 − (EXk )2

Thus if τ is the time to absorption at 0,(C.13)

where α = 1 − 1/N. It follows by taking expectations that themean of the process satisfies the recurrencek

P (Xk = 0) ≤(C.19)

Again, as in Theorem 3, by summing over these estimates, wederive the mean conditional fixation bounds of Theorem 4.

Only an informal outline of the proof is given here. We assume
the representation for the generator G of a GWF process in∂ u(x,t )Theorem 7. Define the operator Lu(x, t ) = Gu(x, t ) − ∂ t . As
discussed in the section on continuum theory, the mean m(x, t )of a process, as a function of initial allele frequency x and timet, satisfies the generalized Kolmogorov equation Lm(x, t ) = 0,
with the boundary conditions m(x, 0) = x, m(0, t ) = 0, andm(1, t ) = 1.
Basic to the proof is an application of the maximum principle,
which is a property of generators of random processes. We look atfunctions u(x, t ) in the rectangle R = {(x, t ) ∈ [0, 1] × [0, T ]}, andlabel three of the respective sides S1 = [0, 1] × 0, S2 = 0 × [0, T ],S3 = 1 × [0, T ]. It can be shown that the following holds (Der,2010).
Lemma 3 (Parabolic Maximum Principle). Let u be continuous on R
and suppose Lu ≥ 0 throughout the interior of R. Thenmax u = max u.
R

S1 ∪S2 ∪S3(C.29)

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R. Der et al. / Theoretical Population Biology 80 (2011) 80–99

That is, the maximum value that any function u takes which satisfies the operator inequality Lu ≥ 0 is achieved on the ‘‘parabolic
boundary’’ S1 ∪ S2 ∪ S3 of the rectangle. A similar ‘‘minimal
principle’’, obtained by reflection, also holds: if for some function
Lu ≤ 0 throughout R, then the minimum of u is also taken on theparabolic boundary. Next, define the following functions:(1 + γ )xm− (x, t ) =1 + γ x + γ (1 − x)e−(1+γ )tm+ (x, t ) =x(1 − γ e−(1−γ )t )(C.30).

1 − γ + γ x(1 − e−(1−γ )t )(C.31)

The functions m− (x, t ) and m+ (x, t ) can be shown, respectively,
to be the means of the marginal distributions of the minimal andmaximal processes, defined earlier in Appendix B. Now we canestablish:
Lemma 4. Let u(x, t ) be a continuous solution on [0, 1] × [0, ∞)to Lu = 0, satisfying the boundary conditions u(x, 0) = x, andu(0, t ) = 0, u(1, t ) = 1 for all time. Thenm− (x, t ) ≤ u(x, t ) ≤ m+ (x, t ),∀(x, t ) ∈ [0, 1] × [0, ∞).

Now we study solutions toGγ ,α u = 0,u(1) = 1

(E.2)

−α
.
or equivalently, Lu = 0, where L = (k/γ )G, with k = γ 13−α
It is important to first analyze the auxiliary operator defined by

L0 u = kxu′ − u + (1 − α)xα−1

∫ x

u(z )

dz .
(E.3)
(x − z )αBy a change of variables, u(x) = xp for p > −1 is an eigenvector of
L0 associated to the eigenvalue λp = kp − 1 +(1 −α)B(p + 1, 1 −α),where B(·, ·) the Beta-function. Since we expect the operator L0 to
mimic that of L near x = 0, we examine the critical points in the0spectrum. Define
S (p) = γ1−α3−αp − 1 + (1 − α)B(p + 1, 1 − α)(E.4)

for values p > −1, 0 < α < 1, γ > 0. The function S has two roots,
one at 0, and another at a generally non-trivial root pr , dependingon γ . It can further be shown that there is exactly one value of γ
for which the double-root pr = 0 occurs, and it happens precisely
when S ′ (0) = 0. Solving this produces the critical value for γ :(C.32)

The foregoing can be proved by verifying that Lm− ≥ 0, and Lm+ ≤0 on R, and then applying the maximal and minimum principles toL(u − m± ) and noting u − m± vanishes on the parabolic boundary.
This suffices already to prove a very strong result: the mean m(x, t )of any GWF process is bounded between m− (x, t ) and m+ (x, t ). By
taking t → ∞ in Lemma 4, we obtain the probability of fixation,and the content of Theorem 6.

u(0) = 0,γ0 = −(3 − α)

∫ 1(1 − t )−α log t dt .

(E.5)

0

Next, note that the operator L can be written as
Lu = L0 u − x(L0 u + u) + (1 − α)x(1 − x)α−1∫ 1
×(z − x)−α u(z ) dz

(E.6)

x

Using the previous observations, one can prove the following
inequality for functions associated to the root pr :C.6. Theorems 7 and 8
We do not give proofs of these mathematical representation
theorems here. Their precise statement and complete proofs canbe found in the thesis Der (2010), and will receive exposition in
future publications.
Appendix D. Fixation probability in the Λ1 -Cannings model
By Theorem 7 and Table 1, the generator for the Λ1 -model withselection is
Gu = γ x(1 − x)u′ (x) + xu(1) + (1 − x)u(0) − u(x)(D.1)

where γ = Ns. The fixation probability π1 (x) is then an equilibrium solution of the generalized backward Kolmogorov equation;that is, Gπ1 = 0. Solving this first-order differential equation subject to the boundary conditions π1 (0) = 0, π1 (1) = 1 leads to theexpression (30).
Appendix E. Assured fixation in power-law models
In this section we establish the property of almost-sure fixation
in some of the power-law models. This property can be extended
to many of the Λ-processes, which will receive exposition in a later
publication. For simplicity we consider the index range 0 < α < 1.
Using Table 1 and the expression in Theorem 7, and integratingby parts it can be shown that the generator for this process underselective coefficient γ = Ns/σ 2 isGγ ,α u(x) = γ x(1 − x)u (x) +
′

3−α



1−α

+ (1 − α)xα−1 (1 − x)

∫ x

−u(x)

(x − z )−α u(z ) dz

0

+ (1 − α)x(1 − x)

α−1

∫ 1
x

(z − x)−αu(z ) dz .

(E.1)

Lemma 5. Let p = pr be the non-trivial root of kp − 1 +(1 −α)B(p +−α1, 1 − α) = 0, where k = γ 31−α
. Setting u(x) = xpr , one has Lu ≥ 0.
Finally, if πα,γ (x) is the probability of fixation for the powerlaw process of index α and selection pressure γ , initialized at allele
frequency x, we can apply the maximum principle in coordination
with the previous lemma to show that it must satisfy
Theorem 9. Let p = pr be the positive root of the equation γ 13−αp−−α
1 + (1 − α)B(p + 1, 1 − α) = 0, with selective pressure 0 < γ < γ0 ,where γ0 is given by (E.5). Thenxpr ≤ πα,γ (x),0 < x < 1.

(E.7)

Theorem 9 reveals an upper bound on the selective pressure
which ensures assured fixation, for every positive initializing
frequency. Since pr ↓ 0 as γ ↑ γ0 , the critical value of assured
fixation γ ∗ satisfies γ ∗ ≤ γ0 , establishing half of the result (31).
The other inequality γ ∗ ≥ γ0 is established in a similar way.
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