Capturing the facets of evolvability in a mechanistic framework
Authors: Jana M. Riederer, Stefano Tiso, Timo J.B. van Eldijk, Franz J. Weissing
Journal: Trends in Ecology & Evolution (2022)

Evolvability, the capability to undergo adaptive evolution, is determined by a staggering diversity of mechanisms and organismal features. When discussing evolvability, it is useful to distinguish three categories of determinants: those providing variation, those shaping the effect of variation on fitness, and those shaping the selection process.Some determinants of evolvability have a broad scope in that they affect adaptive evolution across many different environments; others have a narrower scope in that they impact evolvability only with respect to particular challenges. Being explicit about the scope of evolvability determinants would largely facilitate communication across disciplines.On different timescales, the comparison of organisms regarding their evolvability and the comparison of mechanisms regarding their effects on evolvability can lead to very different conclusions. 'Evolvability' – the ability to undergo adaptive evolution – is a key concept for understanding and predicting the response of biological systems to environmental change. Evolvability has various facets and is applied in many ways, easily leading to misunderstandings among researchers. To clarify matters, we first categorize the mechanisms and organismal features underlying evolvability into determinants providing variation, determinants shaping the effect of variation on fitness, and determinants shaping the selection process. Second, we stress the importance of timescale when studying evolvability. Third, we distinguish between evolvability determinants with a broad and a narrow scope. Finally, we highlight two contrasting perspectives on evolvability: general evolvability and specific evolvability. We hope that this framework facilitates communication and guides future research. 'Evolvability' – the ability to undergo adaptive evolution – is a key concept for understanding and predicting the response of biological systems to environmental change. Evolvability has various facets and is applied in many ways, easily leading to misunderstandings among researchers. To clarify matters, we first categorize the mechanisms and organismal features underlying evolvability into determinants providing variation, determinants shaping the effect of variation on fitness, and determinants shaping the selection process. Second, we stress the importance of timescale when studying evolvability. Third, we distinguish between evolvability determinants with a broad and a narrow scope. Finally, we highlight two contrasting perspectives on evolvability: general evolvability and specific evolvability. We hope that this framework facilitates communication and guides future research. Understanding adaptation to changing environments is more important than ever. Climate change, antibiotic resistance, and viral vaccine evasion represent major societal challenges. Is an endangered species able to adapt to environmental change? Will a bacterial pathogen evolve antibiotic resistance? Can a virus evade vaccine-based immunization? At the core of these issues lies a common element: the capability of organisms to adapt – evolvability [1.Pigliucci M. Is evolvability evolvable?.Nat. Rev. Genet. 2008; 9: 75-82Crossref PubMed Scopus (356) Google Scholar]. Evolvability research sheds new light on genomic architecture [2.Rutten J.P. et al.Adapting the engine to the fuel: mutator populations can reduce the mutational load by reorganizing their genome structure.BMC Evol. Biol. 2019; 19: 1-17Crossref PubMed Scopus (1) Google Scholar], the structure of regulatory networks [3.Wagner A. Robustness and evolvability: a paradox resolved.Proc. Biol. Sci. 2008; 275: 91-100Crossref PubMed Scopus (406) Google Scholar,4.Crombach A. Hogeweg P. Evolution of evolvability in gene regulatory networks.PLoS Comput. Biol. 2008; 4e1000112Crossref PubMed Scopus (147) Google Scholar], and many other features of biological systems (see Glossary). It has yielded surprising new insights, such as: adaptive evolution can proceed at a pace similar to ecological change, resulting in intricate and unexpected ecoevolutionary dynamics [5.Turcotte M.M. et al.The impact of rapid evolution on population dynamics in the wild: experimental test of eco-evolutionary dynamics.Ecol. Lett. 2011; 14: 1084-1092Crossref PubMed Scopus (88) Google Scholar,6.Netz C. et al.Complex eco-evolutionary dynamics induced by the coevolution of predator–prey movement strategies.Evol. Ecol. 2021; (Published online November 16, 2021)https://doi.org/10.1007/s10682-021-10140-xCrossref PubMed Scopus (1) Google Scholar]; evolvability and robustness do not conflict but mutually reinforce each other [3.Wagner A. Robustness and evolvability: a paradox resolved.Proc. Biol. Sci. 2008; 275: 91-100Crossref PubMed Scopus (406) Google Scholar,7.Masel J. Trotter M.V. Robustness and evolvability.Trends Genet. 2010; 26: 406-414Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar,8.Hogeweg P. Toward a theory of multilevel evolution: long-term information integration shapes the mutational landscape and enhances evolvability.in: Soyer O.S. Evolutionary systems biology. Springer, 2012: 195-224Crossref Scopus (13) Google Scholar]; and organisms with high evolvability can 'generalize' over environments [9.Watson R.A. Szathmáry E. How can evolution learn?.Trends Ecol. Evol. 2016; 31: 147-157Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar,10.van Gestel J. Weissing F.J. Regulatory mechanisms link phenotypic plasticity to evolvability.Sci. Rep. 2016; 6: 24524Crossref PubMed Scopus (20) Google Scholar]. Furthermore, evolvability research may add new perspectives to the formulation of a predictive theory of evolution (Box 1 and see Outstanding questions).Box 1Definitions of evolvabilityHere we briefly discuss some definitions of evolvability, as they provide a good overview of the diversity of approaches in the field of evolvability research [63.Brown R.L. What evolvability really is.Br. J. Philos. Sci. 2014; 65: 549-572Crossref Scopus (39) Google Scholar,72.Nuño de la Rosa L. Computing the extended synthesis: mapping the dynamics and conceptual structure of the evolvability research front.J. Exp. Zool. B Mol. Dev. Evol. 2017; 328: 395-411Crossref PubMed Scopus (13) Google Scholar,73.Crother B.I. Murray C.M. Early usage and meaning of evolvability.Ecol. Evol. 2019; 9: 3784-3793Crossref PubMed Scopus (7) Google Scholar]. One important early definition revolves around the additive genetic coefficient of variation. It defines evolvability as the ability to respond to selection as governed by the presence or absence of standing genetic variation (often assessed in the G matrix) [38.Kokko H. et al.Can evolution supply what ecology demands?.Trends Ecol. Evol. 2017; 32: 187-197Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar,58.Houle D. Comparing evolvability and variability of quantitative traits.Genetics. 1992; 130: 195-204Crossref PubMed Google Scholar,74.Hansen T.F. Pélabon C. Evolvability: a quantitative-genetics perspective.Annu. Rev. Ecol. Evol. Syst. 2021; 52: 153-175Crossref Scopus (4) Google Scholar]. Another important perspective was given by Wagner and Altenberg [59.Wagner G.P. Altenberg L. Perspective: complex adaptations and the evolution of evolvability.Evolution. 1996; 50: 967Crossref PubMed Google Scholar], who made a distinction between variation and variability (i.e., the propensity of characters to vary). Evolvability is then considered not as the currently present variation but instead as the ability to generate new variation. A third, different perspective on evolvability considers the ability to generate major innovations [75.Brookfield J.F.Y. Evolution: the evolvability enigma.Curr. Biol. 2001; 11: R106-R108Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar,76.Szathmáry E. Maynard Smith J. The major evolutionary transitions.Nature. 1995; 374: 227-232Crossref PubMed Scopus (535) Google Scholar]. For a comprehensive review of these developments, the reader is referred to [1.Pigliucci M. Is evolvability evolvable?.Nat. Rev. Genet. 2008; 9: 75-82Crossref PubMed Scopus (356) Google Scholar]. Note that these definitions of evolvability are reflected in our first category of determinants, as they all view evolvability as determined by the presence or provisioning of variation.One additional aspect of the definitions of evolvability (also called 'evolutionary potential' or 'adaptive capacity') is the relationship between variation and adaptation. While earlier treatments (as discussed in [1.Pigliucci M. Is evolvability evolvable?.Nat. Rev. Genet. 2008; 9: 75-82Crossref PubMed Scopus (356) Google Scholar]) define evolvability as the ability of a biological system to evolve, irrespective of whether evolution is adaptive or not, recent definitions tend to restrict the concept to adaptive processes. For example, Payne and Wagner [14.Payne J.L. Wagner A. The causes of evolvability and their evolution.Nat. Rev. Genet. 2019; 20: 24-38Crossref PubMed Scopus (101) Google Scholar] combine the aspects of variation and adaptation when they define evolvability as '...the ability of a biological system to produce phenotypic variation that is both heritable and adaptive'. Other definitions in this vein have been provided in [7.Masel J. Trotter M.V. Robustness and evolvability.Trends Genet. 2010; 26: 406-414Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar,38.Kokko H. et al.Can evolution supply what ecology demands?.Trends Ecol. Evol. 2017; 32: 187-197Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar,60.Wagner G.P. Draghi J.A. Evolution of evolvability.in: Evolution – the extended synthesis. MIT Press, 2010: 379-400Crossref Google Scholar,77.Masel J. Siegal M.L. Robustness: mechanisms and consequences.Trends Genet. 2009; 25: 395-403Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar, 78.Hansen T.E. The evolution of genetic architecture.Annu. Rev. Ecol. Evol. Syst. 2006; 37: 123-157Crossref Scopus (247) Google Scholar, 79.Ebner M. et al.On neutral networks and evolvability.in: Proceedings of the 2001 Congress on Evolutionary Computation. 1. IEEE, 2001: 1-8Google Scholar, 80.Zheng J. et al.Selection enhances protein evolvability by increasing mutational robustness and foldability.Science. 2020; 370eabb5962Crossref Scopus (20) Google Scholar, 81.Verd B. et al.Modularity, criticality, and evolvability of a developmental gene regulatory network.eLife. 2019; 8e42832Crossref PubMed Scopus (35) Google Scholar].Following the general trend in the field, we here focus on adaptive evolution as well. When defining evolvability as the 'capability of a biological system to undergo adaptive evolution' we do not mean the presence or absence of this capability, but rather we consider its degree in a continuous fashion. Adopting an adaptive perspective does by no means imply that nonadaptive processes (e.g., genetic drift) are irrelevant; many of the determinants of evolvability reflect such processes (e.g., mutation). However, there are at least two reasons for focussing on adaptive evolution. First, many applications of evolvability (e.g., evolution of antibiotic resistance, adaptation to anthropogenic change) consider the adaptation to environmental challenges. Second, relating the rate and outcome of evolution to underlying selection pressures provides a yardstick, making it possible to differentiate between organismal and environmental features [38.Kokko H. et al.Can evolution supply what ecology demands?.Trends Ecol. Evol. 2017; 32: 187-197Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar] and allowing comparisons across organisms. Both features are important first steps toward a predictive theory of evolution [82.Chevin L.M. et al.Adaptation, plasticity, and extinction in a changing environment: towards a predictive theory.PLoS Biol. 2010; 8e1000357Crossref PubMed Scopus (1157) Google Scholar]. Here we briefly discuss some definitions of evolvability, as they provide a good overview of the diversity of approaches in the field of evolvability research [63.Brown R.L. What evolvability really is.Br. J. Philos. Sci. 2014; 65: 549-572Crossref Scopus (39) Google Scholar,72.Nuño de la Rosa L. Computing the extended synthesis: mapping the dynamics and conceptual structure of the evolvability research front.J. Exp. Zool. B Mol. Dev. Evol. 2017; 328: 395-411Crossref PubMed Scopus (13) Google Scholar,73.Crother B.I. Murray C.M. Early usage and meaning of evolvability.Ecol. Evol. 2019; 9: 3784-3793Crossref PubMed Scopus (7) Google Scholar]. One important early definition revolves around the additive genetic coefficient of variation. It defines evolvability as the ability to respond to selection as governed by the presence or absence of standing genetic variation (often assessed in the G matrix) [38.Kokko H. et al.Can evolution supply what ecology demands?.Trends Ecol. Evol. 2017; 32: 187-197Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar,58.Houle D. Comparing evolvability and variability of quantitative traits.Genetics. 1992; 130: 195-204Crossref PubMed Google Scholar,74.Hansen T.F. Pélabon C. Evolvability: a quantitative-genetics perspective.Annu. Rev. Ecol. Evol. Syst. 2021; 52: 153-175Crossref Scopus (4) Google Scholar]. Another important perspective was given by Wagner and Altenberg [59.Wagner G.P. Altenberg L. Perspective: complex adaptations and the evolution of evolvability.Evolution. 1996; 50: 967Crossref PubMed Google Scholar], who made a distinction between variation and variability (i.e., the propensity of characters to vary). Evolvability is then considered not as the currently present variation but instead as the ability to generate new variation. A third, different perspective on evolvability considers the ability to generate major innovations [75.Brookfield J.F.Y. Evolution: the evolvability enigma.Curr. Biol. 2001; 11: R106-R108Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar,76.Szathmáry E. Maynard Smith J. The major evolutionary transitions.Nature. 1995; 374: 227-232Crossref PubMed Scopus (535) Google Scholar]. For a comprehensive review of these developments, the reader is referred to [1.Pigliucci M. Is evolvability evolvable?.Nat. Rev. Genet. 2008; 9: 75-82Crossref PubMed Scopus (356) Google Scholar]. Note that these definitions of evolvability are reflected in our first category of determinants, as they all view evolvability as determined by the presence or provisioning of variation. One additional aspect of the definitions of evolvability (also called 'evolutionary potential' or 'adaptive capacity') is the relationship between variation and adaptation. While earlier treatments (as discussed in [1.Pigliucci M. Is evolvability evolvable?.Nat. Rev. Genet. 2008; 9: 75-82Crossref PubMed Scopus (356) Google Scholar]) define evolvability as the ability of a biological system to evolve, irrespective of whether evolution is adaptive or not, recent definitions tend to restrict the concept to adaptive processes. For example, Payne and Wagner [14.Payne J.L. Wagner A. The causes of evolvability and their evolution.Nat. Rev. Genet. 2019; 20: 24-38Crossref PubMed Scopus (101) Google Scholar] combine the aspects of variation and adaptation when they define evolvability as '...the ability of a biological system to produce phenotypic variation that is both heritable and adaptive'. Other definitions in this vein have been provided in [7.Masel J. Trotter M.V. Robustness and evolvability.Trends Genet. 2010; 26: 406-414Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar,38.Kokko H. et al.Can evolution supply what ecology demands?.Trends Ecol. Evol. 2017; 32: 187-197Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar,60.Wagner G.P. Draghi J.A. Evolution of evolvability.in: Evolution – the extended synthesis. MIT Press, 2010: 379-400Crossref Google Scholar,77.Masel J. Siegal M.L. Robustness: mechanisms and consequences.Trends Genet. 2009; 25: 395-403Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar, 78.Hansen T.E. The evolution of genetic architecture.Annu. Rev. Ecol. Evol. Syst. 2006; 37: 123-157Crossref Scopus (247) Google Scholar, 79.Ebner M. et al.On neutral networks and evolvability.in: Proceedings of the 2001 Congress on Evolutionary Computation. 1. IEEE, 2001: 1-8Google Scholar, 80.Zheng J. et al.Selection enhances protein evolvability by increasing mutational robustness and foldability.Science. 2020; 370eabb5962Crossref Scopus (20) Google Scholar, 81.Verd B. et al.Modularity, criticality, and evolvability of a developmental gene regulatory network.eLife. 2019; 8e42832Crossref PubMed Scopus (35) Google Scholar]. Following the general trend in the field, we here focus on adaptive evolution as well. When defining evolvability as the 'capability of a biological system to undergo adaptive evolution' we do not mean the presence or absence of this capability, but rather we consider its degree in a continuous fashion. Adopting an adaptive perspective does by no means imply that nonadaptive processes (e.g., genetic drift) are irrelevant; many of the determinants of evolvability reflect such processes (e.g., mutation). However, there are at least two reasons for focussing on adaptive evolution. First, many applications of evolvability (e.g., evolution of antibiotic resistance, adaptation to anthropogenic change) consider the adaptation to environmental challenges. Second, relating the rate and outcome of evolution to underlying selection pressures provides a yardstick, making it possible to differentiate between organismal and environmental features [38.Kokko H. et al.Can evolution supply what ecology demands?.Trends Ecol. Evol. 2017; 32: 187-197Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar] and allowing comparisons across organisms. Both features are important first steps toward a predictive theory of evolution [82.Chevin L.M. et al.Adaptation, plasticity, and extinction in a changing environment: towards a predictive theory.PLoS Biol. 2010; 8e1000357Crossref PubMed Scopus (1157) Google Scholar]. Evolvability is studied by diverse approaches; for instance: Johansson et al. [11.Johansson F. et al.Natural selection mediated by seasonal time constraints increases the alignment between evolvability and developmental plasticity.Evolution. 2021; 75: 464-475Crossref PubMed Scopus (6) Google Scholar] inspect the genetic variance–covariance matrix; Woods et al. [12.Woods R.J. et al.Second-order selection for evolvability in a large Escherichia coli population.Science. 2011; 331: 1433-1436Crossref PubMed Scopus (220) Google Scholar] compare the speed of adaptation of bacterial strains; and Martín-Serra et al. [13.Martín-Serra A. et al.Phenotypic integration and modularity drives skull shape divergence in the Arctic fox (Vulpes lagopus) from the Commander Islands.Biol. Lett. 2019; 15: 20190406Crossref PubMed Scopus (9) Google Scholar] focus on morphological integration and modularity. These approaches, although all valid, are widely disparate: all aim to understand evolvability, yet each focuses on a different facet. This plurality is also reflected in the fact that evolvability has been defined in many different ways (Box 1). We aim to highlight the different facets of evolvability and how they relate to each other, to facilitate a more nuanced and cohesive discourse on the topic. Throughout, we define evolvability as the capability of a biological system to undergo adaptive evolution (see Box 1 for a justification). Evolvability is often viewed in terms of outcomes (e.g., speed of adaptation). As the same outcome can be achieved in many ways, it is useful to study evolvability by a mechanistic approach [14.Payne J.L. Wagner A. The causes of evolvability and their evolution.Nat. Rev. Genet. 2019; 20: 24-38Crossref PubMed Scopus (101) Google Scholar]: viewing evolvability not as a phenomenon per se but as a product of the mechanisms and organismal features that underlie it. A mechanistic perspective also clarifies discussions on the evolution of evolvability [1.Pigliucci M. Is evolvability evolvable?.Nat. Rev. Genet. 2008; 9: 75-82Crossref PubMed Scopus (356) Google Scholar,14.Payne J.L. Wagner A. The causes of evolvability and their evolution.Nat. Rev. Genet. 2019; 20: 24-38Crossref PubMed Scopus (101) Google Scholar]: while questions regarding the evolution of 'the capability to undergo adaptive evolution' easily turn abstract, they become more obvious and transparent when translated into questions regarding the evolution of concrete mechanisms (e.g., the mutation rate). We refer to the mechanisms and organismal features that govern evolvability as determinants of evolvability. These affect different aspects of adaptive evolution and consequently shape evolvability in different ways. We here identify three ways in which determinants can shape evolvability, based on what aspect of adaptive evolution they affect, and categorize them accordingly (Figure 1). First, determinants may affect evolvability by providing variation. The mutation rate is the most obvious example of such a determinant [2.Rutten J.P. et al.Adapting the engine to the fuel: mutator populations can reduce the mutational load by reorganizing their genome structure.BMC Evol. 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Local adaptation, evolutionary potential and host-parasite coevolution: interactions between migration, mutation, population size and generation time.J. Evol. Biol. 2002; 15: 451-462Crossref Scopus (351) Google Scholar]. Heritable variation serves as the raw material for evolution. Hence, our first category refers to those mechanisms that generate and maintain variation. For example, mutations generate variation in many ways, ranging from point mutations to genome rearrangements. Interestingly, mutation rates vary widely between organisms as well as within genomes [24.Sniegowski P.D. et al.The evolution of mutation rates: separating causes from consequences.Bioessays. 2000; 22: 1057-1066Crossref PubMed Scopus (343) Google Scholar, 25.Hodgkinson A. Eyre-Walker A. Variation in the mutation rate across mammalian genomes.Nat. Rev. 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An HSP90-regulated reduced-eye phenotype in Tribolium shows fitness benefits and thus provides evidence for evolutionary capacitance.bioRxiv. 2019; (Published online July 3, 2019)https://doi.org/10.1101/690727Google Scholar,29.Rutherford S.L. Lindquist S. HSP90 as a capacitor for morphological evolution.Nature. 1998; 396: 336-342Crossref PubMed Scopus (1691) Google Scholar]. Developmental canalization can affect evolvability in a similar manner, in that it allows the accumulation of cryptic genetic variation [30.Bergman A. Siegal M.L. Evolutionary capacitance as a general feature of complex gene networks.Nature. 2003; 424: 549-552Crossref PubMed Scopus (377) Google Scholar]. Furthermore, capacitors may also be behavioural in nature, as parental care and thermoregulatory behaviour also allow cryptic genetic variation to accumulate [31.Huey R.B. et al.Behavioral drive versus behavioral inertia in evolution: a null model approach.Am. 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Genet. 2020; 66: 1069-1071Crossref PubMed Scopus (2) Google Scholar]. Not all heritable variation is genetic: epigenetic inheritance, inheritance of environmental features, and cultural inheritance can also affect adaptive evolution [36.Bonduriansky R. Day T. Extended heredity: a new understanding of inheritance and evolution. Princeton University Press, 2018Google Scholar,37.Adrian-Kalchhauser I. et al.Understanding "non-genetic" inheritance: insights from molecular–evolutionary crosstalk.Trends Ecol. Evol. 2020; 35: 1078-1089Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar]. Hence, category 1 also includes mechanisms providing non-genetic heritable variation. The mapping from mutation to fitness is affected by a variety of mechanisms: mutations may be random with respect to the genotype, but their effects on the phenotype and consequently fitness are often not [8.Hogeweg P. Toward a theory of multilevel evolution: long-term information integration shapes the mutational landscape and enhances evolvability.in: Soyer O.S. Evolutionary systems biology. Springer, 2012: 195-224Crossref Scopus (13) Google Scholar]. Through features such as genomic, developmental, and regulatory architecture, the genotype-to-phenotype-to-fitness map can bias the fitness effects of mutations [19.Uller T. et al.Developmental bias and evolution: a regulatory network perspective.Genetics. 2018; 209: 949-966Crossref PubMed Scopus (72) Google Scholar,38.Kokko H. et al.Can evolution supply what ecology demands?.Trends Ecol. Evol. 2017; 32: 187-197Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar]. Category 2 thus contains determinants that influence the effect of variation on fitness. Examples can be found in the evo-devo literature [19.Uller T. et al.Developmental bias and evolution: a regulatory network perspective.Genetics. 2018; 209: 949-966Crossref PubMed Scopus (72) Google Scholar,21.Jernvall J. Linking development with generation of novelty in mammalian teeth.Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 2641-2645Crossref PubMed Scopus (205) Google Scholar,39.Hendrikse J.L. et al.Evolvability as the proper focus of evolutionary developmental biology.Evol. Dev. 2007; 9: 393-401Crossref PubMed Scopus (190) Google Scholar,40.Allen C.E. et al.Differences in the selection response of serially repeated color pattern characters: standing variation, development, and evolution.BMC Evol. Biol. 2008; 8: 1-13Crossref PubMed Scopus (74) Google Scholar], which describes various biases introduced through the developmental process (developmental bias; for an example see the butterfly Bicyclus anynana in Figure 1). The effect of variation on fitness can also be biased by the genomic and regulatory architecture [4.Crombach A. Hogeweg P. Evolution of evolvability in gene regulatory networks.PLoS Comput. Biol. 2008; 4e1000112Crossref PubMed Scopus (147) Google Scholar,41.van Gestel J. Weissing F.J. Is plasticity ca