THE ORIGIN AND EVOLUTION OF LIFE BY MEANS OF ENDO-EXO (ORSELF-NONSELF) CIRCULATION
Masatoshi Murase
Yukawa Institute for Theoretical Physics, Kyoto University,
International Research Unit of Integrated Complex System Science, Kyoto University
Unit of Synergetic Studies for Space, Kyoto University
Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto, Japan 606-8502
Telefax: +81-75-753-7010
murase@yukawa.kyoto-u.ac.jp(Received October 26, 2009; Accepted November 1, 2009)(Abstract)
Concerning the studies of life’s origin, there has beena serious dilemma or a chicken-and-egg paradox how
does evolution starts out of randomly reacting
chemical soup. Actually, evolving units such as
self-replicating polymers could not arise without
evolving processes, whereas evolving processes
would not begin without evolving units. The
processes of life’s origin and its evolution can beconsidered as the continuous complexation of
initially nonliving entities leading to highly complex
living organisms. A concept of self-replicating
polymers alone can not attack the above-mentioned
dilemma, because it can not link different levels of
the hierarchy and hence no complexation appears.
The present paper assumes that self-replicating units
may not be the cause of life’s origin, but instead it
may be the result emerging from quite different
dynamical processes. It is a new paradigm of‘endo-exo (or self-nonself) circulation’ that was
introduced to account for such dynamical processes.

evolution through natural selection [11]; whereas
vesicles (or ‘endo-systems’ [12]) have their own
boundary
membranes
whichcancontainmicro-environment favorable for the polymers, asthese are isolated from the external environment (or‘exo-world’ [12]). Then, I propose the new paradigmof ‘endo-exo (or self-nonself) circulation’ as theinteractive processes between the two different
hierarchical levels such as the endo-system and theexo-world. It is one principle of endo-exo circulationthat would govern the origin and evolution of life,and also would conduct the dynamic organization
typical of the present-day life [29-31].
2. The endo-exo (or self-nonself) theory
Most studies on the origin of life have been
focused on single self-replicating units: either
polymers [1-7] or vesicles [8-10], but not both. Here,I frame a new theory to attack the origin-of-life
problem in two steps.
First, I will consider both random polymers andmembrane-bounded vesicles as illustrated in Figure 1.
Polymers can be future candidates for self-replicating
genetic systems which can help to evolve by natural
selection [11]; while vesicles (or endo-systems [12])have their own boundary membranes which cancreate the micro-environments favorable for suchpolymers, as these are isolated from the externalenvironment (or exo-world [12]).
Then, I will propose the new paradigm of‘endo-exo circulation’ ― instead of self-replication― to specify interactive processes between
endo-system and exo-world. The endo-exo
circulation was possibly driven by cycling
environmentssuchasdrying-wetting(ordehydration-hydration) cycles in tide pools [13].
The resulting circulation would make theendo-system prebiotically evolve [12,14] without
genetic systems, because many different kinds ofmolecules, supplied by the exo-world, could besubject to weak selection [7] through intermolecularinteractions. If self-replicating polymers arise denovo as reliable genetic systems, they would evolve
through natural selection. Thereafter, life would
begin only when an autonomous system of endo-exo
circulation could arise to take over the outside ‘drive’.
It is one principle of endo-exo circulation that would
govern the origin and evolution of life.
To develop a new theory for the origin of life, I
assume that life’s origin and its evolution would be
the continuous complexation of initially non-living― yet highly interacting ― entities, and therefore,(Keywords)
Endo-exo circulation, origin and evolution of life,
dynamical organization
1. Introduction
It is the traditional reductionists’ view thatidentifies the constituent elements of a complex
biological system and studies the relationship among
the elements at different levels. However, there arises
one serious problem concerning the traditional
reductionism: it is hard to understand how livingorganism is different from nonliving matter, as bothare equally made of material molecules. To study life
itself and its origin, which must be quite different
from nonliving matter, we should identify not only
the constituent elements but also the elementary
processes within and beyond the organism.
Traditionally, studies on the origin of life havebeen focused on self-replicating units: either
one-dimensional polymers [1-7] or three-dimensional
vesicles [8-10], but not both. Because there were nointeractive processes between the two different
hierarchical levels such as polymers and vesicles,
most studies have failed to explain how initiallynonliving entities show continuous complification
ultimately leading to the origin of life.
In the present paper, I first assume that there areboth random polymers and membrane-boundedvesicles. Polymers can be future candidate forself-replicating genetic systems responsible for its
Viva Origino 39 (2011) 7 - 10
© 2011 by SSOEL Japan-7-Viva Origino 39 (2011) 7 - 10

Figure 1. The new paradigm of endo-exo circulation. A
closed vesicle (or an endo -system) can keep its identity
as it has the boundary membranes which isolate themicro-environment from the exo-world. Suppose thatsuch a closed vesicle is subject to assembly-disassembly
cycles (see the lower panel): that is, the boundary
membranes are broken, allowing entry of molecules fromthe exo-world (as called encapsulation [13,24]), andresealed. Here fragments of membranes and individual
molecules are indicated by arcs and dots, respectively. At
each cycle, the vesicle could not retain the same
composition as it was before, but instead ‘evolve’ in aspiral way (see the upper panel): indeed, it can create new
combinations of molecules involved which might besubject to weak selection through intermolecularinteractions, and therefore, it can reach beyond theboundaries of its identity (as called self-transcendence[14]). In addition, the enclosed micro-environment canprovide a basis for open evolution, because an almost
infinite number of molecules are supplied by theexo-world at every cycle. I refer such interactive
processes between endo-system and exo-world asendo-exo circulation. Note that the endo-exo circulation
can link different levels of the hierarchy such asindividual molecules, polymers, membranes and vesicles.
As a result, the endo-system can undergo continuouscomplexation with the emergence of new levels of thehierarchy.

Figure 2. The co-evolution of polymers and vesicles
through endo-exo circulation, driven by drying-wetting
cycles. Such cycling environments are initially requiredas the outside ‘drive’ (see the bottom panel). During
dehydration, polymerization reactions are driven; andvesicles tend to fuse into multilayered structures that
could trap solutes within single membranes or between
alternating membranes, thereby bringing a variety ofmolecules into close contact with one another (see themiddle panel). Here, membranes are indicated by circles(on the left side) or straight lines (on the right side).
Polymers and monomers are represented by curves anddots, respectively. Through intermolecular interactions,the molecules might be weakly selected at any instance.
Upon hydration, many kinds of polymers and vesicles
would be produced. Some vesicles could encapsulate
nearby solutes, including polymers. There may, of course,
be some amount of truncation selection removing vesicles
that develop too weak membrane structures to maintainthemselves. In this sense, selection would occur at any
level of the hierarchy. During another round of
dehydration, the encapsulated pre-existing polymers
would have an ordering effect on other encapsulatedmonomers, because they could serve as ‘templates’ todirect replication effectively in a narrow space ofmultilayered structures [13]. Upon rehydration, manydifferent vesicles are formed again from multilayered
structures, some of which would enclose the solute
molecules including original templates and several copies.
The first self-replicating polymers, transposable elements,
and protoviruses would be driven to co-evolve before theautonomous cellular life (see the top panel). Note that
self-replication is the derived character of the endo-exocirculation. The origin of autonomous cellular life can bedefined by the events that an autonomous system ofendo-exo circulation would arise to take over the outside‘drive’.

one principle could govern a great diversity ofdynamic phenomena at any instance and level of thehighly interacting entities. Conversely, we canidentify the unique principle essential to the origin oflife by investigating the dynamic organization ―involving both structures and processes ― typical ofpresent-day life [29-31].
3. The ModelWithin this framework, I first consider bothrandom polymers and membrane-bounded vesicles as
the least hierarchical structures required for the originof life. Strictly, I assume that there were at least twovery different kinds of molecules as illustrated in
Figure 2. One is monomeric molecules that canreadily form one-dimensional polymers upon
dehydration [15]. The other is amphipathic molecules― characterized by both hydrophilic ‘heads’ andhydrophobic ‘tails’ on the single molecules like
phospholipids ― that can spontaneously aggregate toform two-dimensional bilayer membranes and to-8-

Viva Origino 39 (2011) 7 - 10

create three-dimensional closed vesicles (orliposomes) in an aqueous solution [16,17].
The two different kinds of molecules thus frame
quite different degrees of freedom or different levelsof hierarchy, and hence, it is easy to create thedivision of labor among the molecules: linear
polymers are plausible candidates for genetic systems,
bilayer membranes of a closed vesicle are interfaces
between the inside and the outside, and the closed
vesicle provides the micro-environment as a chemical
reactor where nutrient molecules and energy are
constantly supplied by the external environment.
Both polymers and vesicles, therefore, must be theleast hierarchical structures required for the origin oflife.

genetic systems, because such polymers maintainidentity by self-replication and yet undergo
Darwinian evolution through variation and naturalselection. Resent studies on present-day cells,
however, suggest that the membrane processes ―such as the growth, budding and fusion of plasma
membranes and vesicles, together with the membranetransport and membrane transduction ― are notdirectly controlled by genetic systems, and still they
are essential for adaptive behavior of cells, biogenesisof intracellular organelles and many other functions[25-26]. Of course, such present-day membraneprocesses are ascribed to endo-exo circulation rather
than self-replication, because vesicles, organelles orcells are individually viewed as endo-systems that areundergoing variation with respect to combinations ofmolecules.
What mechanisms initially drive the endo-exo
circulation on the prebiotic Earth? Note that there
were two very different kinds of molecules:
monomeric molecules readily forming linear
polymers upon dehydration [15] and amphipathic
molecules spontaneously aggregating to create closed
vesicles
uponhydration[16-17].
Thus,
dehydration-hydration cycles [13] can be one of theplausible mechanisms of the endo-exo circulation, bywhich many different kinds of polymers and vesicles
are alternately generated and degenerated. Suchdrying-wetting cycles must have occurred in theprebiotic environment, particularly at intertidal zones,
just as today [24]. Although emphasis was placed on
the encapsulation of various solutes by closed
vesicles [13], this evidence suggests that thedehydration-hydration cycles would drive theendo-exo circulation.
Since selection upon pre-existing variability
implies evolution, polymers and vesicles would
prebiotically co-evolve through endo-exo circulation,
if there are two events in a cycle:

4. Discussion
Despite the requirement that both polymers andvesicles must be present as the least hierarchicallydifferent structures, most studies have traditionallybeen focused on either polymers or vesicles withemphasis on the process of self-replication, and so,many difficulties remained to be solved. Three of themajor difficulties are:
(i)

(ii)

(iii)

self-replicating polymers [1-7] alone
never evolve de novo out of random
polymers without other pre-evolving
systems [18-20] nor the bounded
complexsystemrequiredforautocatalysis [6];self-replicating vesicles [8-10] alone
never evolve by natural selection,
because thy lack stored information in astable way based on self-replicating
polymers [21]:even if there are self-replicating polymers
along with vesicles, proto-cells would notoriginate without any dynamic process
between the two units, because bilayer
membranes are effective barriers to ionicsolutes, hydrophilic metabolites andmany other molecules [22-24].

(i)

Considering all the difficulties as a whole, we are
faced with one serious dilemma: without evolving
processes evolving units (e.g., self-replicating
polymers and proto-cells) could not arise, but without
evolving units no evolutionary processes would begin.
There must be some key process other thanself-replication which could link different levels of
the hierarchy, leading to life’s origin and its
evolution.
Now, we need paradigm shifts in the key processof adaptive evolution from ‘self-replication’ to‘endo-exo circulation’. Figure 1 illustrates, how aclosed vesicle (or endo-system [12]) not only shows
identity in contrast with the open vesicle (orexo-world [12]), but also undergoes prebiotic
evolution through variation and weak selection in thecontext of a combination of molecules involved.
Traditionally, identity and evolution have been
ascribed to the same self-replicating polymers or(ii)formation of a great diversity at all levelsof the hierarchy such as individual
molecules, linear polymers, bilayer
membranes and closed vesicles;
selection at all levels of the hierarchy
through intermolecular interactions (seeFigure 2).

The enclosed micro-environment can be achemical reactor where many different kinds ofmolecules are supplied by the exo-world, thereby
providing a chemical basis for ‘the RNA world’ [3],involving
ribozymes[27-28].
The
first
self-replicating polymers could arise in the RNA
world, and thereafter they could evolve throughnatural selection. In this sense, self-replication,
typical of genetic polymers, can be the emergent
property of the endo-exo circulation. If, in addition,
self-splicing (or inversely self-inserting) introns
evolve in the RNA world, they could create new
combinations of polymers, like transposable elements.
Such ‘selfish’ elements would become genetic
parasites or infectious viruses when encapsulated by-9-

Viva Origino 39 (2011) 7 - 10protective coats.
Traditionally, it seems likely that viruses musthave evolved after cells, as they depend on their hostcells for biosynthesis. The present theory, however,suggests alternative possibility: no cellular life could
originate without an autonomous system of endo-exocirculation, but yet encapsulated ‘selfish’ elements orprotoviruses could arise de novo as long as theoutside ‘drive’ persists. The origin of life is thendefined by the events that some autonomous systemof endo-exo circulation would arise to take over theoutside ‘drive’. Whereas endo-exo circulation links
different levels of the hierarchy, leading to the originof protocells; self-replication has no such effects,
although it can undergo Darwinian evolution throughnatural selection. Only the principle of endo-exo
circulation, therefore, determines the continuous
complexation with the emergence of new levels oforganization in the hierarchy, resulting in thediversity of life [29-31].
Acknowledgement
I am grateful to all the participants who attended
the four successive international workshops: “What isLife?” in 2007, “What is Creativity?” in 2008, “Whatis Evolution?” in 2009 and “Novel Phenomena in
Integrated Complex Sciences” in 2010 supported byYukawa Institute for Theoretical Physics of theKyoto University.
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