An environmentally induced multicellular life cycle of a unicellular cyanobacterium.

Understanding the evolutionary transition to multicellularity is a key problem in biology.1,2,3,4 Nevertheless, the ecological conditions driving such transitions are not well understood. The first known transition to multicellularity occurred 2.5 billion years ago in cyanobacteria,5,6,7 and today's cyanobacteria are characterized by enormous morphological diversity. They range from unicellular species; unicellular cyanobacteria with packet-like phenotypes, e.g., tetrads; and simple filamentous species to highly differentiated filamentous species.8,9,10 The cyanobacterium Cyanothece sp. ATCC 51142, an isolate from the intertidal zone of the U.S. Gulf Coast,11 was classified as a unicellular species.12 We report a facultative life cycle of Cyanothece sp. in which multicellular filaments alternate with unicellular stages. In a series of experiments, we identified salinity and population density as environmental factors triggering the phenotypic switch between the two morphologies. Then, we used numerical models to test hypotheses regarding the nature of the environmental cues and the mechanisms underlying filament dissolution. While the results predict that the observed response is likely caused by an excreted compound in the medium, we cannot fully exclude changes in nutrient availability (as in Tuomi et al.13 and Matz and Jürgens14). The best-fit modeling results show a nonlinear effect of the compound, which is characteristic of density-dependent sensing systems.15,16 Furthermore, filament fragmentation is predicted to occur by connection cleavage rather than cell death of each alternating cell, which is supported by fluorescent and scanning electron microscopy results. The switch between unicellular and multicellular morphology constitutes an environmentally dependent life cycle that is likely an important step en route to permanent multicellularity.

Eco-evolutionary dynamics of clonal multicellular life cycles.

The evolution of multicellular life cycles is a central process in the course of the emergence of multicellularity. The simplest multicellular life cycle is comprised of the growth of the propagule into a colony and its fragmentation to give rise to new propagules. The majority of theoretical models assume selection among life cycles to be driven by internal properties of multicellular groups, resulting in growth competition. At the same time, the influence of interactions between groups on the evolution of life cycles is rarely even considered. Here, we present a model of colonial life cycle evolution taking into account group interactions. Our work shows that the outcome of evolution could be coexistence between multiple life cycles or that the outcome may depend on the initial state of the population - scenarios impossible without group interactions. At the same time, we found that some results of these simpler models remain relevant: evolutionary stable strategies in our model are restricted to binary fragmentation - the same class of life cycles that contains all evolutionarily optimal life cycles in the model without interactions. Our results demonstrate that while models neglecting interactions can capture short-term dynamics, they fall short in predicting the population-scale picture of evolution.

The evolutionary dynamics of extrachromosomal DNA in human cancers.

Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Currently, the impact of nonchromosomal oncogene inheritance-random identity by descent-is poorly understood. Also unclear is the impact of ecDNA on somatic variation and selection. Here integrating theoretical models of random segregation, unbiased image analysis, CRISPR-based ecDNA tagging with live-cell imaging and CRISPR-C, we demonstrate that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment. Observed ecDNAs benefit host cell survival or growth and can change within a single cell cycle. ecDNA inheritance can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are facilitated by the ability of ecDNA to rapidly adapt genomes in a way that is not possible through chromosomal oncogene amplification. These results show how the nonchromosomal random inheritance pattern of ecDNA contributes to poor outcomes for patients with cancer.

Evolution of reproductive strategies in incipient multicellularity.

Multicellular organisms potentially show a large degree of diversity in reproductive strategies, producing offspring with varying sizes and compositions compared to their unicellular ancestors. In reality, only a few of these reproductive strategies are prevalent. To understand why this could be the case, we develop a stage-structured population model to probe the evolutionary growth advantages of reproductive strategies in incipient multicellular organisms. The performance of reproductive strategies is evaluated by the growth rates of the corresponding populations. We identify the optimal reproductive strategy, leading to the largest growth rate for a population. Considering the effects of organism size and cellular interaction, we found that distinct reproductive strategies could perform uniquely or equally well under different conditions. If a single reproductive strategy is optimal, it is binary splitting, dividing into two parts. Our results show that organism size and cellular interaction can play crucial roles in shaping reproductive strategies in nascent multicellularity. Our model sheds light on understanding the mechanism driving the evolution of reproductive strategies in incipient multicellularity. Beyond multicellularity, our results imply that a crucial factor in the evolution of unicellular species' reproductive strategies is organism size.

The possible modes of microbial reproduction are fundamentally restricted by distribution of mass between parent and offspring.

Multiple modes of asexual reproduction are observed among microbial organisms in natural populations. These modes are not only subject to evolution, but may drive evolutionary competition directly through their impact on population growth rates. The most prominent transition between two such modes is the one from unicellularity to multicellularity. We present a model of the evolution of reproduction modes, where a parent organism fragments into smaller parts. While the size of an organism at fragmentation, the number of offspring, and their sizes may vary a lot, the combined mass of fragments is limited by the mass of the parent organism. We found that mass conservation can fundamentally limit the number of possible reproduction modes. This has important direct implications for microbial life: For unicellular species, the interplay between cell shape and kinetics of the cell growth implies that the largest and the smallest possible cells should be rod shaped rather than spherical. For primitive multicellular species, these considerations can explain why rosette cell colonies evolved a mechanistically complex binary split reproduction. Finally, we show that the loss of organism mass during sporulation can explain the macroscopic sizes of the formally unicellular microorganism Myxomycetes plasmodium. Our findings demonstrate that a number of seemingly unconnected phenomena observed in unrelated species may be different manifestations of the same underlying process.

Evolution of irreversible somatic differentiation.

A key innovation emerging in complex animals is irreversible somatic differentiation: daughters of a vegetative cell perform a vegetative function as well, thus, forming a somatic lineage that can no longer be directly involved in reproduction. Primitive species use a different strategy: vegetative and reproductive tasks are separated in time rather than in space. Starting from such a strategy, how is it possible to evolve life forms which use some of their cells exclusively for vegetative functions? Here, we develop an evolutionary model of development of a simple multicellular organism and find that three components are necessary for the evolution of irreversible somatic differentiation: (i) costly cell differentiation, (ii) vegetative cells that significantly improve the organism's performance even if present in small numbers, and (iii) large enough organism size. Our findings demonstrate how an egalitarian development typical for loose cell colonies can evolve into germ-soma differentiation dominating metazoans.

Limb reduction in squamate reptiles correlates with the reduction of the chondrocranium: A case study on serpentiform anguids.

BACKGROUND: In vertebrates, the skull evolves from a complex network of dermal bones and cartilage-the latter forming the pharyngeal apparatus and the chondrocranium. Squamates are particularly important in this regard as they maintain at least part of the chondrocranium throughout their whole ontogeny until adulthood. Anguid lizards represent a unique group of squamates, which contains limbed and limbless forms and show conspicuous variation of the adult skull. RESULTS: Based on several emboadryonic stages of the limbless lizards Pseudopus apodus and Anguis fragilis, and by comparing with other squamates, we identified and interpreted major differences in chondrocranial anatomy. Among others, the most important differences are in the orbitotemporal region. P. apodus shows a strikingly similar development of this region to other squamates. Unexpectedly, however, A. fragilis differs considerably in the composition of the orbitotemporal region. In addition, A. fragilis retains a paedomorphic state of the nasal region. CONCLUSIONS: Taxonomic comparisons indicate that even closely related species with reduced limbs show significant differences in chondrocranial anatomy. The Pearson correlation coefficient suggests strong correlation between chondrocranial reduction and limb reduction. We pose the hypothesis that limb reduction could be associated with the reduction in chondrocrania by means of genetic mechanisms.

Evolution of multicellular life cycles under costly fragmentation.

A fascinating wealth of life cycles is observed in biology, from unicellularity to the concerted fragmentation of multicellular units. However, the understanding of factors driving their evolution is still limited. We show that costs of fragmentation have a major impact on the evolution of life cycles due to their influence on the growth rates of the associated populations. We model a group structured population of undifferentiated cells, where cell clusters reproduce by fragmentation. Fragmentation events are associated with a cost expressed by either a fragmentation delay, an additional risk, or a cell loss. The introduction of such fragmentation costs vastly increases the set of possible life cycles. Based on these findings, we suggest that the evolution of life cycles involving splitting into multiple offspring can be directly associated with the fragmentation cost. Moreover, the impact of this cost alone is strong enough to drive the emergence of multicellular units that eventually split into many single cells, even under scenarios that strongly disfavour collectives compared to solitary individuals.

Why is cyclic dominance so rare?

Natural populations can contain multiple types of coexisting individuals. How does natural selection maintain such diversity within and across populations? A popular theoretical basis for the maintenance of diversity is cyclic dominance, illustrated by the rock-paper-scissor game. However, it appears difficult to find cyclic dominance in nature. Why is this the case? Focusing on continuously produced novel mutations, we theoretically addressed the rareness of cyclic dominance. We developed a model of an evolving population and studied the formation of cyclic dominance. Our results showed that the chance for cyclic dominance to emerge is lower when the newly introduced type is similar to existing types compared to the introduction of an unrelated type. This suggests that cyclic dominance is more likely to evolve through the assembly of unrelated types whereas it rarely evolves within a community of similar types.

Meta-population structure and the evolutionary transition to multicellularity.

The evolutionary transition to multicellularity has occurred on numerous occasions, but transitions to complex life forms are rare. Here, using experimental bacterial populations as proxies for nascent multicellular organisms, we manipulate ecological factors shaping the evolution of groups. Groups were propagated under regimes requiring reproduction via a life cycle replete with developmental and dispersal (propagule) phases, but in one treatment lineages never mixed, whereas in a second treatment, cells from different lineages experienced intense competition during the dispersal phase. The latter treatment favoured traits promoting cell growth at the expense of traits underlying group fitness - a finding that is supported by results from a mathematical model. Our results show that the transition to multicellularity benefits from ecological conditions that maintain discreteness not just of the group (soma) phase, but also of the dispersal (germline) phase.

Interacting cells driving the evolution of multicellular life cycles.

Evolution of complex multicellular life began from the emergence of a life cycle involving the formation of cell clusters. The opportunity for cells to interact within clusters provided them with an advantage over unicellular life forms. However, what kind of interactions may lead to the evolution of multicellular life cycles? Here, we combine evolutionary game theory with a model for the emergence of multicellular groups to investigate how cell interactions can influence reproduction modes during the early stages of the evolution of multicellularity. In our model, the presence of both cell types is maintained by stochastic phenotype switching during cell division. We identify evolutionary optimal life cycles as those which maximize the population growth rate. Among all interactions captured by two-player games, the vast majority promotes two classes of life cycles: (i) splitting into unicellular propagules or (ii) fragmentation into two offspring clusters of equal (or almost equal) size. Our findings indicate that the three most important characteristics, determining whether multicellular life cycles will evolve, are the average performance of homogeneous groups, heterogeneous groups, and solitary cells.

Evolution of simple multicellular life cycles in dynamic environments.

The mode of reproduction is a critical characteristic of any species, as it has a strong effect on its evolution. As any other trait, the reproduction mode is subject to natural selection and may adapt to the environment. When the environment varies over time, different reproduction modes could be optimal at different times. The natural response to a dynamic environment seems to be bet hedging, where multiple reproductive strategies are stochastically executed. Here, we develop a framework for the evolution of simple multicellular life cycles in a dynamic environment. We use a matrix population model of undifferentiated multicellular groups undergoing fragmentation and ask which mode maximizes the population growth rate. Counterintuitively, we find that natural selection in dynamic environments generally tends to promote deterministic, not stochastic, reproduction modes.

Population size changes and extinction risk of populations driven by mutant interactors.

Spontaneous random mutations are an important source of variation in populations. Many evolutionary models consider mutants with a fixed fitness, chosen from a fitness distribution without considering microscopic interactions among the residents and mutants. Here, we go beyond this and consider "mutant interactors," which lead to new interactions between the residents and invading mutants that can affect the population size and the extinction risk of populations. We model microscopic interactions between individuals by using a dynamic interaction matrix, the dimension of which increases with the emergence of a new mutant and decreases with extinction. The new interaction parameters of the mutant follow a probability distribution around the payoff entries of its ancestor. These new interactions can drive the population away from the previous equilibrium and lead to changes in the population size. Thus, the population size is an evolving property rather than an externally controlled variable. We calculate the average population size of our stochastic system over time and quantify the extinction risk of the population by the mean time to extinction.

Fragmentation modes and the evolution of life cycles.

Reproduction is a defining feature of living systems. To reproduce, aggregates of biological units (e.g., multicellular organisms or colonial bacteria) must fragment into smaller parts. Fragmentation modes in nature range from binary fission in bacteria to collective-level fragmentation and the production of unicellular propagules in multicellular organisms. Despite this apparent ubiquity, the adaptive significance of fragmentation modes has received little attention. Here, we develop a model in which groups arise from the division of single cells that do not separate but stay together until the moment of group fragmentation. We allow for all possible fragmentation patterns and calculate the population growth rate of each associated life cycle. Fragmentation modes that maximise growth rate comprise a restrictive set of patterns that include production of unicellular propagules and division into two similar size groups. Life cycles marked by single-cell bottlenecks maximise population growth rate under a wide range of conditions. This surprising result offers a new evolutionary explanation for the widespread occurrence of this mode of reproduction. All in all, our model provides a framework for exploring the adaptive significance of fragmentation modes and their associated life cycles.

Modes of migration and multilevel selection in evolutionary multiplayer games.

The evolution of cooperation in group-structured populations has received much attention, but little is known about the effects of different modes of migration of individuals between groups. Here, we have incorporated four different modes of migration that differ in the degree of coordination among the individuals. For each mode of migration, we identify the set of multiplayer games in which the cooperative strategy has higher fixation probability than defection. The comparison shows that the set of games under which cooperation may evolve generally expands depending upon the degree of coordination among the migrating individuals. Weak altruism can evolve under all modes of individual migration, provided that the benefit to cost ratio is high enough. Strong altruism, however, evolves only if the mode of migration involves coordination of individual actions. Depending upon the migration frequency and degree of coordination among individuals, conditions that allow selection to work at the level of groups can be established.