The evolution of life on earth has been driven by a small number of major evolutionary transitions. These transitions have been characterized by individuals that could previously replicate independently, cooperating to form a new, more complex life form. For example, archaea and eubacteria formed eukaryotic cells, and cells formed multicellular organisms. However, not all cooperative groups are en route to major transitions. How can we explain why major evolutionary transitions have or haven't taken place on different branches of the tree of life? We break down major transitions into two steps: the formation of a cooperative group and the transformation of that group into an integrated entity. We show how these steps require cooperation, division of labor, communication, mutual dependence, and negligible within-group conflict. We find that certain ecological conditions and the ways in which groups form have played recurrent roles in driving multiple transitions. In contrast, we find that other factors have played relatively minor roles at many key points, such as within-group kin discrimination and mechanisms to actively repress competition. More generally, by identifying the small number of factors that have driven major transitions, we provide a simpler and more unified description of how life on earth has evolved.T he evolution of life, from simple organic compounds in a primordial soup to the amazing diversity of contemporary organisms, has taken roughly 3.5 billion years. How can we explain the evolution of increasingly complex organisms over this period? A traditional approach has been to consider the succession of taxonomic groups, such as the age of fishes giving rise to the age of amphibians, which gave way to the age of reptiles, and so on. Although this approach has some uses, it is biased toward relatively large plants and animals and lacks a conceptual or predictive framework, in that it suggests we look for different explanations for each succession (1).Twenty years ago, Maynard Smith and Szathmáry (2) revolutionized our understanding of life on earth by showing how the key steps in the evolution of life on earth had been driven by a small number of "major evolutionary transitions." In each transition, a group of individuals that could previously replicate independently cooperate to form a new, more complex life form. For example, genes cooperated to form genomes, archaea and eubacteria formed eukaryotic cells, and cells cooperated to form multicellular organisms (Table 1).The major transitions approach provides a conceptual framework that facilitates comparison across pivotal moments in the history of life (2, 3). It suggests that the same problem arises at each transition: How are the potentially selfish interests of individuals overcome to form mutually dependent cooperative groups? We can then ask whether there are any similarities across transitions in the answers to this problem. Consequently, rather than looking for different explanations for the succession of different taxonomic groups, we ...

Organisms across the tree of life form symbiotic partnerships with microbes for metabolism, protection and resources. While some hosts evolve extreme dependence on their symbionts, others maintain facultative associations. Explaining this variation is fundamental to understanding when symbiosis can lead to new higher-level individuals, such as during the evolution of the eukaryotic cell. Here we perform phylogenetic comparative analyses on 106 unique host–bacterial symbioses to test for correlations between symbiont function, transmission mode, genome size and host dependence. We find that both transmission mode and symbiont function are correlated with host dependence, with reductions in host fitness being greatest when nutrient-provisioning, vertically transmitted symbionts are removed. We also find a negative correlation between host dependence and symbiont genome size in vertically, but not horizontally, transmitted symbionts. These results suggest that both function and population structure are important in driving irreversible dependence between hosts and symbionts.

The evolution of multicellular organisms represents one of approximately eight major evolutionary transitions that have occurred on earth. The major challenge raised by this transition is to explain why single cells should join together and become mutually dependent, in a way that leads to a more complex multicellular life form that can only replicate as a whole. It has been argued that a high genetic relatedness (r) between cells played a pivotal role in the evolutionary transition from single-celled to multicellular organisms, because it leads to reduced conflict and an alignment of interests between cells. We tested this hypothesis with a comparative study, comparing the form of multicellularity in species where groups are clonal (r = 1) to species where groups are potentially nonclonal (r ≤ 1). We found that species with clonal group formation were more likely to have undergone the major evolutionary transition to obligate multicellularity and had more cell types, a higher likelihood of sterile cells, and a trend toward higher numbers of cells in a group. More generally, our results unify the role of group formation and genetic relatedness across multiple evolutionary transitions and provide an unmistakable footprint of how natural selection has shaped the evolution of life.

Pioglitazone (5-(4-(2-(5-ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione, 2) is a prototypical antidiabetic thiazolidinedione that had been evaluated for possible clinical development. Metabolites 6-9 have been identified after dosing of rats and dogs. Ketone 10 has not yet been identified as a metabolite but has been added to the list as a putative metabolite by analogy to alcohol 6 and ketone 7. We have developed improved syntheses of pioglitazone (2) metabolites 6-9 and the putative metabolite ketone 10. These entities have been compared in the KKAy mouse model of human type-II diabetes to pioglitazone (2). Ketone 10 has proven to be the most potent of these thiazolidinedinediones in this in vivo assay. When 6-10 were compared in vitro in the 3T3-L1 cell line to 2, for their ability to augment insulin-stimulated lipogenesis, 10 was again the most potent compound with 6, 7 and 9 roughly equivalent to 2. These data suggest that metabolites 6, 7 and 9 are likely to contribute to the pharmacological activity of pioglitazone (2), as had been previously reported for ciglitazone (1).

21Elevated nutrient levels can lead to excessive biofilm growth, but reducing nutrient 22 pollution is often challenging. There is therefore interest in developing control 23 measures for biofilm growth in nutrient-rich rivers that could act as complement to 24 direct reductions in nutrient load. Shading of rivers is one option that can mitigate 25blooms, but few studies have experimentally examined the differences in biofilm 26 communities grown under shaded and unshaded conditions. We investigated the 27 assembly and diversity of biofilm communities using in situ mesocosms within the 28 River Thames (UK). Biofilm composition was surveyed by 454 sequencing of 16S 29 amplicons (~400 bp length covering regions V6/V7). The results confirm the 30 importance of sunlight for biofilm community assembly; a resource that was utilized 31 by a relatively small number of dominant taxa, leading to significantly less diversity 32 than in shaded communities. These differences between unshaded and shaded were 33 either because of differences in resource utilization or loss of diatom-structures as 34 habitats for bacteria. We observed more co-occurrence patterns and network 35 interactions in the shaded communities. This lends further support to the proposal that 36 increased river shading can help mitigate the effects from macronutrient pollution in 37 rivers. 38 39 Introduction 40

A major challenge in evolutionary biology has been to explain the variation in multicellularity across the many independently evolved multicellular lineages, from slime moulds to vertebrates. Social evolution theory has highlighted the key role of relatedness in determining multicellular complexity and obligateness; however, there is a need to extend this to a broader perspective incorporating the role of the environment. In this paper, we formally test Bonner's 1998 hypothesis that the environment is crucial in determining the course of multicellular evolution, with aggregative multicellularity evolving more frequently on land and clonal multicellularity more frequently in water. Using a combination of scaling theory and phylogenetic comparative analyses, we describe multicellular organizational complexity across 139 species spanning 14 independent transitions to multicellularity and investigate the role of the environment in determining multicellular group formation and in imposing constraints on multicellular evolution. Our results, showing that the physical environment has impacted the way in which multicellular groups form, highlight that environmental conditions might have affected the major evolutionary transition to obligate multicellularity.

Understanding how and why cells cooperate to form multicellular organisms is a central aim of evolutionary biology. Multicellular groups can form through clonal development (where daughter cells stick to mother cells after division) or by aggregation (where cells aggregate to form groups). These different ways of forming groups directly affect relatedness between individual cells, which in turn can influence the degree of cooperation and conflict within the multicellular group. It is hard to study the evolution of multicellularity by focusing only on obligately multicellular organisms, like complex animals and plants, because the factors that favour multicellular cooperation cannot be disentangled, as cells cannot survive and reproduce independently. We support the use of Saccharomyces cerevisiae as an ideal model for studying the very first stages of the evolution of multicellularity. This is because it can form multicellular groups both clonally and through aggregation and uses a family of proteins called ‘flocculins’ that determine the way in which groups form, making it particularly amenable to laboratory experiments. We briefly review current knowledge about multicellularity in S. cerevisiae and then propose a framework for making predictions about the evolution of multicellular phenotypes in yeast based on social evolution theory. We finish by explaining how S. cerevisiae is a particularly useful experimental model for the analysis of open questions concerning multicellularity.

Division of labour between different specialized cell types is a central part of how we describe complexity in multicellular organisms. However, it is increasingly being recognized that division of labour also plays an important role in the lives of predominantly unicellular organisms. Saccharomyces cerevisiae displays several phenotypes that could be considered a division of labour, including quiescence, apoptosis and biofilm formation, but they have not been explicitly treated as such. We discuss each of these examples, using a definition of division of labour that involves phenotypic variation between cells within a population, cooperation between cells performing different tasks and maximization of the inclusive fitness of all cells involved. We then propose future research directions and possible experimental tests using S. cerevisiae as a model organism for understanding the genetic mechanisms and selective pressures that can lead to the evolution of the very first stages of a division of labour. Copyright © 2017 John Wiley & Sons, Ltd.