The Evolutionary Origin of Somatic Cells under the Dirty Work Hypothesis

Reproductive division of labor is a hallmark of multicellular organisms. However, the evolutionary pressures that give rise to delineated germ and somatic cells remain unclear. Here we propose a hypothesis that the mutagenic consequences associated with performing metabolic work favor such differentiation. We present evidence in support of this hypothesis gathered using a computational form of experimental evolution. Our digital organisms begin each experiment as undifferentiated multicellular individuals, and can evolve computational functions that improve their rate of reproduction. When such functions are associated with moderate mutagenic effects, we observe the evolution of reproductive division of labor within our multicellular organisms. Specifically, a fraction of the cells remove themselves from consideration as propagules for multicellular offspring, while simultaneously performing a disproportionately large amount of mutagenic work, and are thus classified as soma. As a consequence, other cells are able to take on the role of germ, remaining quiescent and thus protecting their genetic information. We analyze the lineages of multicellular organisms that successfully differentiate and discover that they display unforeseen evolutionary trajectories: cells first exhibit developmental patterns that concentrate metabolic work into a subset of germ cells (which we call “pseudo-somatic cells”) and later evolve to eliminate the reproductive potential of these cells and thus convert them to actual soma. We also demonstrate that the evolution of somatic cells enables phenotypic strategies that are otherwise not easily accessible to undifferentiated organisms, though expression of these new phenotypic traits typically includes negative side effects such as aging.     

Multicellularity, stem cells, and the neoblasts of the planarian Schmidtea mediterranea

All multicellular organisms depend on stem cells for their survival and perpetuation. Their central role in reproductive, embryonic, and post-embryonic processes, combined with their wide phylogenetic distribution in both the plant and animal kingdoms intimates that the emergence of stem cells may have been a prerequisite in the evolution of multicellular organisms. We present an evolutionary perspective on stem cells and extend this view to ascertain the value of current comparative studies on various invertebrate and vertebrate somatic and germ line stem cells. We suggest that somatic stem cells may be ancestral, with germ line stem cells being derived later in the evolution of multicellular organisms. We also propose that current studies of stem cell biology are likely to benefit from studying the somatic stem cells of simple metazoans. Here, we present the merits of neoblasts, a largely unexplored, yet experimentally accessible population of stem cells found in the planarian Schmidtea mediterranea. We introduce what we know about the neoblasts, and posit some of the questions that will need to be addressed in order to better resolve the relationship between planarian somatic stem cells and those found in other organisms, including humans.     

Organism size promotes the evolution of specialized cells in multicellular digital organisms

Specialized cells are the essence of complex multicellular life. Fossils allow us to study the modification of specialized, multicellular features such as jaws, scales, and muscular appendages. But it is still unclear what organismal properties contributed to the transition from undifferentiated organisms, which contain only a single cell type, to multicellular organisms with specialized cells. Using digital organisms I studied this transition. My simulations show that the transition to specialized cells happens faster in organism composed of many cells than in organisms composed of few cells. Large organisms suffer less from temporarily unsuccessful evolutionary experiments with individual cells, allowing them to evolve specialized cells via evolutionary trajectories that are unavailable to smaller organisms. This demonstrates that the evolution of simple multicellular organisms which are composed of many functionally identical cells accelerates the evolution of more complex organisms with specialized cells.     

Adaptive mutation in Saccharomyces cerevisiae

Adaptive mutation is a generic term for processes that allow individual cells of nonproliferating cell populations to acquire advantageous mutations and thereby to overcome the strong selective pressure of proliferation-limiting environmental conditions. Prerequisites for an occurrence of adaptive mutation are that the selective conditions are nonlethal and that a restart of proliferation may be accomplished by some genetic change in principle. The importance of adaptive mutation is derived from the assumption that it may, on the one hand, result in an accelerated evolution of microorganisms and, on the other, in multicellular organisms may contribute to a breakout of somatic cells from negative growth regulation, i.e., to cancerogenesis. Most information on adaptive mutation in eukaryotes has been gained with the budding yeast Saccharomyces cerevisiae. This review focuses comprehensively on adaptive mutation in this organism and summarizes our current understanding of this issue.     

Stem cells as probabilistic self-producing entities

Stem cells have the capacity both to self-renew and to give rise to differentiated progeny, and are vital to the organization of multicellular organisms. Stem cells raise a number of fundamental questions regarding lineage restriction and cellular differentiation, and they hold enormous promise for cell-based therapies. Here I propose a theoretical framework for stem cell biology based on the concepts of autopoiesis (self-production) and complementarity. I argue that stem cells are pivotal in the self-production of the organism and that we need complementary approaches to understand their probabilistic behavior. I discuss how this framework generates testable hypotheses regarding stem-cell functions.     

Genetic engineering of the multicellular green alga Volvox: a modified and multiplied bacterial antibiotic resistance gene as a dominant selectable marker

The green alga Volvox represents the simplest multicellular organism: Volvax is composed of only two cell types, somatic and reproductive. Volvox, therefore, is an attractive model system for studying various aspects of multicellularity. With the biolistic nuclear transformation of Volvox carteri, the powerful molecular genetic manipulation of this organism has been established, but applications have been restricted to an auxotrophic mutant serving as the DNA recipient. Therefore, a dominant selectable marker working in all strains and mutants of this organism is required. Among several gene constructs tested, the most advantageous results were obtained with a chimeric gene composed of the coding sequence of the bacterial ble gene, conferring resistance to the antibiotic zeocin, modified with insertions of two endogenous introns from the Volvox arylsulfatase gene and fused to 5' and 3' untranslated regions from the Volvox beta 2-tubulin gene. In the most suitable plasmid used, the gene dosage was increased 16-fold by a technique that allows exponential multiplication of a DNA fragment. Co-transformation of this plasmid and a non-selectable plasmid allowed the identification of zeocin resistant transformants with nuclear integration of both selectable and non-selectable plasmids. Stable expression of the ble gene and of genes from several non-selectable plasmids is demonstrated. The modified ble gene provides the first dominant marker for transformation of both wild-type and mutant strains of Volvox.     

Adaptive Mutation in Saccharomyces cerevisiae

ABSTRACT

Adaptive mutation is a generic term for processes that allow individual cells of nonproliferating cell populations to acquire advantageous mutations and thereby to overcome the strong selective pressure of proliferation-limiting environmental conditions. Prerequisites for an occurrence of adaptive mutation are that the selective conditions are nonlethal and that a restart of proliferation may be accomplished by some genetic change in principle. The importance of adaptive mutation is derived from the assumption that it may, on the one hand, result in an accelerated evolution of microorganisms and, on the other, in multicellular organisms may contribute to a breakout of somatic cells from negative growth regulation, i.e., to cancerogenesis. Most information on adaptive mutation in eukaryotes has been gained with the budding yeast Saccharomyces cerevisiae. This review focuses comprehensively on adaptive mutation in this organism and summarizes our current understanding of this issue.     

昆虫卵子发生过程中细胞凋亡的研究进展

细胞凋亡是动物发育过程中的基本生命现象,是多细胞生物体一种重要的自我稳定机制。除体细胞发生凋亡外,生殖细胞在其发生过程中也有细胞凋亡。对近10年来昆虫卵子发生过程中细胞凋亡的研究作了综述。重点关注昆虫卵子发生过程中细胞凋亡发生的阶段、凋亡的形态特征、凋亡的调控及意义等,以期为相关研究提供基础资料。     

ON THE PARADIGM OF ALTRUISTIC SUICIDE IN THE UNICELLULAR WORLD

Altruistic suicide is best known in the context of programmed cell death (PCD) in multicellular individuals, which is understood as an adaptive process that contributes to the development and functionality of the organism. After the realization that PCD‐like processes can also be induced in single‐celled lineages, the paradigm of altruistic cell death has been extended to include these active cell death processes in unicellular organisms. Here, we critically evaluate the current conceptual framework and the experimental data used to support the notion of altruistic suicide in unicellular lineages, and propose new perspectives. We argue that importing the paradigm of altruistic cell death from multicellular organisms to explain active death in unicellular lineages has the potential to limit the types of questions we ask, thus biasing our understanding of the nature, origin, and maintenance of this trait. We also emphasize the need to distinguish between the benefits and the adaptive role of a trait. Lastly, we provide an alternative framework that allows for the possibility that active death in single‐celled organisms is a maladaptive trait maintained as a byproduct of selection on pro‐survival functions, but that could—under conditions in which kin/group selection can act—be co‐opted into an altruistic trait.     

Environmentally induced responses co-opted for reproductive altruism

Reproductive altruism is an extreme form of altruism best typified by sterile castes in social insects and somatic cells in multicellular organisms. Although reproductive altruism is central to the evolution of multicellularity and eusociality, the mechanistic basis for the evolution of this behaviour is yet to be deciphered. Here, we report that the gene responsible for the permanent suppression of reproduction in the somatic cells of the multicellular green alga, Volvox carteri, evolved from a gene that in its unicellular relative, Chlamydomonas reinhardtii, is part of the general acclimation response to various environmental stress factors, which includes the temporary suppression of reproduction. Furthermore, we propose a model for the evolution of soma, in which by simulating the acclimation signal (i.e. a change in cellular redox status) in a developmental rather than environmental context, responses beneficial to a unicellular individual can be co-opted into an altruistic behaviour at the group level. The co-option of environmentally induced responses for reproductive altruism can contribute to the stability of this behaviour, as the loss of such responses would be costly for the individual. This hypothesis also predicts that temporally varying environments, which will select for more efficient acclimation responses, are likely to be more conducive to the evolution of reproductive altruism.     

Multilevel selection favors fragmentation modes that maintain cooperative interactions in multispecies communities

Reproduction is one of the requirements for evolution and a defining feature of life. Yet, across the tree of life, organisms reproduce in many different ways. Groups of cells (e.g., multicellular organisms, colonial microbes, or multispecies biofilms) divide by releasing propagules that can be single-celled or multicellular. What conditions determine the number and size of reproductive propagules? In multicellular organisms, existing theory suggests that single-cell propagules prevent the accumulation of deleterious mutations (e.g., cheaters). However, groups of cells, such as biofilms, sometimes contain multiple metabolically interdependent species. This creates a reproductive dilemma: small daughter groups, which prevent the accumulation of cheaters, are also unlikely to contain the species diversity that is required for ecological success. Here, we developed an individual-based, multilevel selection model to investigate how such multi-species groups can resolve this dilemma. By tracking the dynamics of groups of cells that reproduce by fragmenting into smaller groups, we identified fragmentation modes that can maintain cooperative interactions. We systematically varied the fragmentation mode and calculated the maximum mutation rate that communities can withstand before being driven to extinction by the accumulation of cheaters. We find that for groups consisting of a single species, the optimal fragmentation mode consists of releasing single-cell propagules. For multi-species groups we find various optimal strategies. With migration between groups, single-cell propagules are favored. Without migration, larger propagules sizes are optimal; in this case, group-size dependent fissioning rates can prevent the accumulation of cheaters. Our work shows that multi-species groups can evolve reproductive strategies that allow them to maintain cooperative interactions.     

Differences in cell division rates drive the evolution of terminal differentiation in microbes

Multicellular differentiated organisms are composed of cells that begin by developing from a single pluripotent germ cell. In many organisms, a proportion of cells differentiate into specialized somatic cells. Whether these cells lose their pluripotency or are able to reverse their differentiated state has important consequences. Reversibly differentiated cells can potentially regenerate parts of an organism and allow reproduction through fragmentation. In many organisms, however, somatic differentiation is terminal, thereby restricting the developmental paths to reproduction. The reason why terminal differentiation is a common developmental strategy remains unexplored. To understand the conditions that affect the evolution of terminal versus reversible differentiation, we developed a computational model inspired by differentiating cyanobacteria. We simulated the evolution of a population of two cell types -nitrogen fixing or photosynthetic- that exchange resources. The traits that control differentiation rates between cell types are allowed to evolve in the model. Although the topology of cell interactions and differentiation costs play a role in the evolution of terminal and reversible differentiation, the most important factor is the difference in division rates between cell types. Faster dividing cells always evolve to become the germ line. Our results explain why most multicellular differentiated cyanobacteria have terminally differentiated cells, while some have reversibly differentiated cells. We further observed that symbioses involving two cooperating lineages can evolve under conditions where aggregate size, connectivity, and differentiation costs are high. This may explain why plants engage in symbiotic interactions with diazotrophic bacteria.     

Derivation of rigorous conditions for high cell-type diversity by algebraic approach

The development of a multicellular organism is a dynamic process. Starting with one or a few cells, the organism develops into different types of cells with distinct functions. We have constructed a simple model by considering the cell number increase and the cell-type order conservation, and have assessed conditions for cell-type diversity. This model is based on a stochastic Lindenmayer system with cell-to-cell interactions for three types of cells. In the present model, we have successfully derived complex but rigorous algebraic relations between the proliferation and transition rates for cell-type diversity by using a symbolic method: quantifier elimination (QE). Surprisingly, three modes for the proliferation and transition rates have emerged for large ratios of the initial cells to the developed cells. The three modes have revealed that the equality between the development rates for the highest cell-type diversity is reduced during the development process of multicellular organisms. Furthermore, we have found that the highest cell-type diversity originates from order conservation.     

Fundamental taboos of biology

This paper formulates some taboos relating to living systems and cognition of these systems: in nature, there exist no two identical living complex multicellular organisms; there is no way to create an exact copy of a multicellular organism; there is no way to obtain two identical clones of a unicellular organism if they contain a sufficiently large number of cells; based on comparing present-day organisms, it is impossible to restore the structure of the first living cell and the processes that have led to its emergence; it is impossible to create a living cell from its separate simple constituents; the mechanisms determining cell vitality are essentially incognizable.     

Molecular phylogeny of the volvocine flagellates.

Phylogenetic studies of approximately 2,000 bases of sequence from the large and small nuclear-encoded ribosomal RNAs are used to investigate the origins of the genus Volvox. The colonial and multicellular genera currently placed in the family Volvocaceae form a monophyletic group that is significantly closer phylogenetically to Chlamydomonas reinhardtii than it is to the other unicellular green flagellates that were tested, including Chlamydomonas eugametos, Chlorella pyrenoidosa, and Haematococcus lacustris. Statistical analysis of 251 phylogenetically informative nucleotide positions rejects the "volvocine lineage" hypothesis, which postulates a monophyletic evolutionary progression from unicellular organisms (such as Chlamydomonas), through colonial organisms (e.g., Gonium, Pandorina, Eudorina, and Pleodorina) demonstrating increasing size, cell number, and tendency toward cellular differentiation, to multicellular organisms having fully differentiated somatic and reproductive cells (in the genus Volvox). The genus Volvox appears not to be monophyletic. Volvox capensis falls outside a lineage containing other representatives of Volvox (V. aureus, V. carteri, and V. obversus), and both of these Volvox lineages are more closely related to certain colonial genera than they are to each other. This implies either a diphyletic origin of Volvox from different colonial volvocacean ancestors, a phylogenetic derivation of some of the colonial genera from a multicellular (i.e., Volvox) ancestor, or both. Considered together with previously published observations, these results suggest that the different levels of organizational and developmental complexity found in the Volvocaceae represent alternative stable states, among which evolutionary transitions have occurred several times during the phylogenetic history of this group.     

In Caenorhabditis elegans Nanoparticle-Bio-Interactions Become Transparent: Silica-Nanoparticles Induce Reproductive Senescence

While expectations and applications of nanotechnologies grow exponentially, little is known about interactions of engineered nanoparticles with multicellular organisms. Here we propose the transparent roundworm Caenorhabditis elegans as a simple but anatomically and biologically well defined animal model that allows for whole organism analyses of nanoparticle-bio-interactions. Microscopic techniques showed that fluorescently labelled nanoparticles are efficiently taken up by the worms during feeding, and translocate to primary organs such as epithelial cells of the intestine, as well as secondary organs belonging to the reproductive tract. The life span of nanoparticle-fed Caenorhabditis elegans remained unchanged, whereas a reduction of progeny production was observed in silica-nanoparticle exposed worms versus untreated controls. This reduction was accompanied by a significant increase of the ‘bag of worms’ phenotype that is characterized by failed egg-laying and usually occurs in aged wild type worms. Experimental exclusion of developmental defects suggests that silica-nanoparticles induce an age-related degeneration of reproductive organs, and thus set a research platform for both, detailed elucidation of molecular mechanisms and high throughput screening of different nanomaterials by analyses of progeny production.