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Similar efficacies of selection shape mitochondrial and nuclear genes in Drosophila melanogaster and Homo sapiens

Deleterious mutations contribute to polymorphism even when selection effectively prevents their fixation. The efficacy of selection in removing deleterious mitochondrial mutations from populations depends on the effective population size (Ne) of the mtDNA, and the degree to which a lack of recombination magnifies the effects of linked selection. Using complete mitochondrial genomes from Drosophila melanogaster and nuclear data available from the same samples, we re-examine the hypothesis that non-recombining animal mtDNA harbor an excess of deleterious polymorphisms relative to the nuclear genome. We find no evidence of recombination in the mitochondrial genome, and the much-reduced level of mitochondrial synonymous polymorphism relative to nuclear genes is consistent with a reduction in Ne. Nevertheless, we find that the neutrality index (NI), a measure of the excess of nonsynonymous polymorphism relative to the neutral expectation, is not significantly different between mitochondrial and nuclear loci. Reanalysis of published data from Homo sapiens reveals the same lack of a difference between the two genomes, though small samples in previous studies had suggested a strong difference in both species. Thus, despite a smaller Ne, mitochondrial loci of both flies and humans appear to experience similar efficacies of selection as do loci in the recombining nuclear genome.

Evolutionary Biology

Social evolution and genetic interactions in the short and long term

The evolution of social traits remains one of the most fascinating and feisty topics in evolutionary bi-ology even after half a century of theoretical research. W. D. Hamilton shaped much of the field initially with his 1964 papers that laid out the foundation for understanding the effect of genetic relatedness on the evolution of social behavior. Early theoretical investigations revealed two critical assumptions required for Hamiltons rule to hold in dynamical models: weak selection and additive genetic interactions. However, only recently have analytical approaches from population genetics and evolutionary game theory developed sufficiently so that social evolution can be studied under the joint action of selection, mutation, and genetic drift. We review how these approaches suggest two timescales for evolution under weak mutation: (i) a short-term timescale where evolution occurs between a finite set of alleles, and (ii) a long-term timescale where a continuum of alleles are possible and populations evolve continuously from one monomorphic trait to another. We show how Hamiltons rule emerges from the short-term analysis under additivity and how non-additive genetic interactions can be accounted for more generally. This short-term approach re-produces, synthesizes, and generalizes many previous results including the one-third law from evolutionary game theory and risk dominance from economic game theory. Using the long-term approach, we illustrate how trait evolution can be described with a diffusion equation that is a stochastic analogue of the canonical equation of adaptive dynamics. Peaks in the stationary distribution of the diffusion capture classic notions of convergence stability from evolutionary game theory and generally depend on the additive genetic in-teractions inherent in Hamiltons rule. Surprisingly, the peaks of the long-term stationary distribution can predict the effects of simple kinds of non-additive interactions. Additionally, the peaks capture both weak and strong effects of social payoffs in a manner difficult to replicate with the short-term approach. Together, the results from the short and long-term approaches suggest both how Hamiltons insight may be robust in unexpected ways and how current analytical approaches can expand our understanding of social evolution far beyond Hamiltons original work.

Evolutionary Biology

Heterochrony explains convergent testis evolution in primates

In independent mammalian lineages where females mate with multiple males (multi-male mating strategies), males have evolved larger testicles relative to those lineages where females mate with fewer males (single-male mating strategies). Here we study published bulk testis transcriptomes from humans, chimpanzees, gorillas and rhesus macaques, as well as mice and rats. Employing a formal model of adaptive evolution, we find that testis transcriptomes have also evolved convergently, reflecting each species mating strategy. Using deconvolution, we infer that testis transcriptome divergence patterns largely reflect convergent shifts in tissue cell type composition. However, we also identify modest amounts of convergent evolution at the cell-autonomous level by analyzing cell-type specific transcriptome data from spermatids and spermatocytes. We further show that in the single-male mating primates, human and gorilla, testis transcriptome profiles are paedomorphic relative to those of multi-male primates, chimpanzee and macaque, suggesting that shifts in timing or rate of testis development could underlie convergent changes in testis mass, histology, and transcriptomes.

Evolutionary Biology

Deciphering the genetic and transcriptional basis of cross-stress responses in Escherichia coli under complex evolutionary scenarios

A tantalizing question in microbial physiology is the inter-dependence and evolutionary potential of cellular stress response across multiple environmental dimensions. To address this question, we comprehensively characterized the cross-stress behavior of wild-type and evolved Escherichia coli populations in five abiotic stresses (n-butanol, osmotic, alkaline, acidic, and oxidative) by performing genome-scale genetic, transcriptional and growth profiling, thus identifying 18 cases of cross-stress protection and one case of cross-stress vulnerability. We identified 18 cases of cross-stress protection and one case of cross-stress vulnerability, along with core and stress-specific networks. We tested several hypotheses regarding the effect of the stress order, stress combinations, mutation reversal and varying environments to the evolution and final cellular fitness of the respective populations. Our results argue of a common systems-level core of the stress response with several crucial implicated pathways that include metal ion binding and glycolysis/gluconeogenesis that is further complemented by a stress-specific expression program.

Evolutionary Biology

Bayesian analyses of Yemeni mitochondrial genomes suggest multiple migration events with Africa and Western Eurasia

Anatomically modern humans (AMHs) left Africa {small tilde}60,000 years ago, marking the first of multiple dispersal events by AMH between Africa and the Arabian Peninsula. The southern dispersal route (SDR) out of Africa (OOA) posits that early AMHs crossed the Bab el-Mandeb strait from the Horn of Africa into what is now Yemen and followed the coast of the Indian Ocean into eastern Eurasia. If AMHs followed the SDR and left modern descendants in situ, Yemeni populations should retain old autochthonous mitogenome lineages. Alternatively, if AMHs did not follow the SDR or did not leave modern descendants in the region, only young autochthonous lineages will remain as evidence of more recent dispersals. We sequenced 113 whole mitogenomes from multiple Yemeni regions with a focus on haplogroups M, N, and L3(xM,N) as they are considered markers of the initial OOA migrations. We performed Bayesian evolutionary analyses to generate time-measured phylogenies calibrated by Neanderthal and Denisovan mitogenome sequences in order to determine the age of Yemeni-specific clades in our dataset. Our results indicate that the M1, N1, and L3(xM,N) sequences in Yemen are the product of recent migration from Africa and western Eurasia. Although these data suggest that modern Yemeni mitogenomes are not markers of the original OOA migrants, we hypothesize that recent population dynamics may obscure any genetic signature of an ancient SDR migration.

Evolutionary Biology

A systematic survey of an intragenic epistatic landscape

Mutations are the source of evolutionary variation. The interactions of multiple mutations can have important effects on fitness and evolutionary trajectories. We have recently described the distribution of fitness effects of all single mutations for a nine amino acid region of yeast Hsp90 (Hsp82) implicated in substrate binding. Here, we report and discuss the distribution of intragenic epistatic effects within this region in seven Hsp90 point mutant backgrounds of neutral to slightly deleterious effect, resulting in an analysis of more than 1000 double-mutants. We find negative epistasis between substitutions to be common, and positive epistasis to be rare - resulting in a pattern that indicates a drastic change in the distribution of fitness effects one step away from the wild type. This can be well explained by a concave relationship between phenotype and genotype (i.e., a concave shape of the local fitness landscape), suggesting mutational robustness intrinsic to the local sequence space. Structural analyses indicate that, in this region, epistatic effects are most pronounced when a solvent-inaccessible position is involved in the interaction. In contrast, all 18 observations of positive epistasis involved at least one mutation at a solvent-exposed position. By combining the analysis of evolutionary and biophysical properties of an epistatic landscape, these results contribute to a more detailed understanding of the complexity of protein evolution.

Evolutionary Biology

Introns structure patterns of variation in nucleotide composition in Arabidopsis thaliana and rice protein-coding genes

Plant genomes are large, intron-rich and present a wide range of variation in coding region G + C content. Concerning coding regions, a sort of syndrome can be described in plants: the increase in G + C content is associated with both the increase in heterogeneity among genes within a genome and the increase in variation across genes. Taking advantage of the large number of genes composing plant genomes and the wide range of variation in gene intron number, we performed a comprehensive survey of the patterns of variation in G + C content at different scales from the nucleotide level to the genome scale in two species Arabidopsis thaliana and Oryza sativa, comparing the patterns in genes with different intron numbers. In both species, we observed a pervasive effect of gene intron number and location along genes on G + C content, codon and amino acid frequencies suggesting that in both species, introns have a barrier effect structuring G + C content along genes. In external gene regions (located upstream first or downstream last intron), species-specific factors are shaping G + C content while in internal gene regions (surrounded by introns), G + C content is constrained to remain within a range common to both species. In rice, introns appear as a major determinant of gene G + C content while in A. thaliana introns have a weaker but significant effect. The structuring effect of introns in both species is susceptible to explain the G + C content syndrome observed in plants.

Evolutionary Biology

Comparative genomics reveals the origins and diversity of arthropod immune systems

While the innate immune system of insects is well-studied, comparatively little is known about how other arthropods defend themselves against infection. We have characterised key immune components in the genomes of five chelicerates, a myriapod and a crustacean. We found clear traces of an ancient origin of innate immunity, with some arthropods havingToll-like receptors and C3-complement factors that are more closely related in sequence or structure to vertebrates than other arthropods. Across the arthropods some components of the immune system, like the Toll signalling pathway, are highly conserved. However, there is also remarkable diversity. The chelicerates apparently lack the Imd signalling pathway and BGRPs - a key class of pathogen recognition receptors. Many genes have large copy number variation across species, and this may sometimes be accompanied by changes in function. For example, peptidoglycan recognition proteins (PGRPs) have frequently lost their catalytic activity and switch between secreted and intracellular forms. There has been extensive duplication of the cellular immune receptor Dscam in several species, which may be an alternative way to generate the high diversity that produced by alternativesplicing in insects. Our results provide a detailed analysis of the immune systems of several important groups of animals and lay the foundations for functional work on these groups.

Evolutionary Biology

Analyses of Eurasian wild and domestic pig genomes reveals long-term gene-flow during domestication

Traditionally, the process of domestication is assumed to be initiated by people, involve few individuals and rely on reproductive isolation between wild and domestic forms. However, an emerging zooarcheological consensus depicts animal domestication as a long-term process without reproductive isolation or strong intentional selection. Here, we ask whether pig domestication followed a traditional linear model, or a complex, reticulate model as predicted by zooarcheologists. To do so, we fit models of domestication to whole genome data from over 100 wild and domestic pigs. We found that the assumptions of traditional models, such as reproductive isolation and strong domestication bottlenecks, are incompatible with the genetic data and provide support for the zooarcheological theory of a complex domestication process. In particular, gene-flow from wild to domestic pigs was a ubiquitous feature of the domestication of pigs. In addition, we show that despite gene-flow, the genomes of domestic pigs show strong signatures of selection at loci that affect behaviour and morphology. Specifically, our results are consistent with independent parallel sweeps in two independent domestication areas (China and Anatolia) at loci linked to morphological traits. We argue that recurrent selection for domestic traits likely counteracted the homogenising effect of gene-flow from wild boars and created \"islands of domestication\" in the genome. Overall, our results suggest that genomic approaches that allow for more complex models of domestication to be embraced should be employed. The results from these studies will have significant ramifications for studies that attempt to infer the origin of domesticated animals.\n\nSignificance StatementThough animal domestication has traditionally been viewed as a human-directed process involving small populations of domestic animals and limited interbreeding between wild and domestic forms, but recent zooarcheological insights have questioned this model. By studying domestication in pigs, we demonstrate that complex models of domestication incorporating long-term gene-flow from multiple wild boar populations fit genomic data from modern wild and domestic pigs significantly better than models based on the traditional perspective. In addition, we demonstrate that selection at genes associated with domestic traits countered the effects of the gene flow, thus allowing morphological and behavioural differentiation between wild and domestic populations to be maintained.

Evolutionary Biology

E. coli populations in unpredictably fluctuating environments evolve to face novel stresses through enhanced efflux activity

There is considerable understanding about how laboratory populations respond to predictable (constant or deteriorating-environment) selection for single environmental variables like temperature or pH. However, such insights may not apply when selection environments comprise multiple variables that fluctuate unpredictably, as is common in nature. To address this issue, we grew replicate laboratory populations of E. coli in nutrient broth whose pH and concentrations of salt (NaCl) and hydrogen peroxide (H2O2) were randomly changed daily. After [~]170 generations, the fitness of the selected populations had not increased in any of the three selection environments. However, these selected populations had significantly greater fitness in four novel environments which have no known fitness-correlation with tolerance to pH, NaCl or H2O2. Interestingly, contrary to expectations, hypermutators did not evolve. Instead, the selected populations evolved an increased ability for energy dependent efflux activity that might enable them to throw out toxins, including antibiotics, from the cell at a faster rate. This provides an alternate mechanism for how evolvability can evolve in bacteria and potentially lead to broad spectrum antibiotic resistance, even in the absence of prior antibiotic exposure. Given that environmental variability is increasing in nature, this might have serious consequences for public-health.

Evolutionary Biology

GC-content evolution in bacterial genomes: the biased gene conversion hypothesis expands.

The characterization of functional elements in genomes relies on the identification of the footprints of natural selection. In this quest, taking into account neutral evolutionary processes such as mutation and genetic drift is crucial because these forces can generate patterns that may obscure or mimic signatures of selection. In mammals, and probably in many eukaryotes, another such confounding factor called GC-Biased Gene Conversion (gBGC) has been documented. This mechanism generates patterns identical to what is expected under selection for higher GC-content, specifically in highly recombining genomic regions. Recent results have suggested that a mysterious selective force favouring higher GC-content exists in Bacteria but the possibility that it could be gBGC has been excluded. Here, we show that gBGC is probably at work in most if not all bacterial species. First we find a consistent positive relationship between the GC-content of a gene and evidence of intra-genic recombination throughout a broad spectrum of bacterial clades. Second, we show that the evolutionary force responsible for this pattern is acting independently from selection on codon usage, and could potentially interfere with selection in favor of optimal AU-ending codons. A comparison with data from human populations shows that the intensity of gBGC in Bacteria is comparable to what has been reported in mammals. We propose that gBGC is not restricted to sexual Eukaryotes but also widespread among Bacteria and could therefore be an ancestral feature of cellular organisms. We argue that if gBGC occurs in bacteria, it can account for previously unexplained observations, such as the apparent non-equilibrium of base substitution patterns and the heterogeneity of gene composition within bacterial genomes. Because gBGC produces patterns similar to positive selection, it is essential to take this process into account when studying the evolutionary forces at work in bacterial genomes.

Evolutionary Biology

Epidemiological and evolutionary analysis of the 2014 Ebola virus outbreak

The 2014 epidemic of the Ebola virus is governed by a genetically diverse viral population. In the early Sierra Leone outbreak, a recent study has identified new mutations that generate genetically distinct sequence clades [1]. Here we find evidence that major Sierra Leone clades have systematic differences in growth rate and reproduction number. If this growth heterogeneity remains stable, it will generate major shifts in clade frequencies and influence the overall epidemic dynamics on time scales within the current outbreak. Our method is based on simple summary statistics of clade growth, which can be inferred from genealogical trees with an underlying clade-specific birth-death model of the infection dynamics. This method can be used to perform realtime tracking of an evolving epidemic and identify emerging clades of epidemiological or evolutionary significance.

Evolutionary Biology

A Hidden Markov Model for Investigating Recent Positive Selection through Haplotype Structure

Recent positive selection can increase the frequency of an advantageous mutant rapidly enough that a relatively long ancestral haplotype will be remained intact around it. We present a hidden Markov model (HMM) to identify such haplotype structures. With HMM identified haplotype structures, a population genetic model for the extent of ancestral haplotypes is then adopted for parameter inference of the selection intensity and the allele age. Simulations show that this method can detect selection under a wide range of conditions and has higher power than the existing frequency spectrum-based method. In addition, it provides good estimate of the selection coefficients and allele ages for strong selection. The method analyzes large data sets in a reasonable amount of running time. This method is applied to HapMap III data for a genome scan, and identifies a list of candidate regions putatively under recent positive selection. It is also applied to several genes known to be under recent positive selection, including the LCT, KITLG and TYRP1 genes in Northern Europeans, and OCA2 in East Asians, to estimate their allele ages and selection coefficients.

Evolutionary Biology

Increased evolutionary rate in the 2014 West African Ebola outbreak is due to transient polymorphism and not positive selection

Gire et al. (Science 345:1369-1372, 2014) analyzed 81 complete genomes sampled from the 2014 Zaire ebolavirus (EBOV) outbreak and reported \"rapid accumulation of [...] genetic variation\" and a substitution rate that was \"roughly twice as high within the 2014 outbreak as between outbreaks.\" These findings have received widespread attention, and many have perceived Gire et al. (2014)s results as implying rapid adaptation of EBOV to humans during the current outbreak. Here, we argue that, on the contrary, sequence divergence in EBOV is rather limited, and that the currently available data contain no robust signal of particularly rapid evolution or adaptation to humans. The doubled substitution rate can be attributed entirely to the application of a molecular-clock model to a population of sequences with minimal divergence and segregating polymorphisms. Our results highlight how subtle technical aspects of sophisticated evolutionary analysis methods may result in highly-publicized, misconstrued statements about an ongoing public health crisis.

Evolutionary Biology

How Well Can We Detect Shifts in Rates of Lineage Diversification? A Simulation Study of Sequential AIC Methods

Evolutionary biologists have long been fascinated by the extreme differences in species numbers across branches of the Tree of Life. This has motivated the development of statistical phylogenetic methods for detecting shifts in the rate of lineage diversification (speciation - extinction). One of the most frequently used methods--implemented in the program MEDUSA--explores a set of diversification-rate models, where each model uniquely assigns branches of the phylogeny to a set of one or more diversification-rate categories. Each candidate model is first fit to the data, and the Akaike Information Criterion (AIC) is then used to identify the optimal diversification model. Surprisingly, the statistical behavior of this popular method is completely unknown, which is a concern in light of the poor performance of the AIC as a means of choosing among models in other phylogenetic comparative contexts, and also because of the ad hoc algorithm used to visit models. Here, we perform an extensive simulation study demonstrating that, as implemented, MEDUSA (1) has an extremely high Type I error rate (on average, spurious diversification-rate shifts are identified 42% of the time), and (2) provides severely biased parameter estimates (on average, estimated net-diversification and relative-extinction rates are 183% and 20% of their true values, respectively). We performed simulation experiments to reveal the source(s) of these pathologies, which include (1) the use of incorrect critical thresholds for model selection, and (2) errors in the likelihood function. Understanding the statistical behavior of MEDUSA is critical both to empirical researchers--in order to clarify whether these methods can reliably be applied to empirical datasets--and to theoretical biologists--in order to clarify whether new methods are required, and to reveal the specific problems that need to be solved in order to develop more reliable approaches for detecting shifts in the rate of lineage diversification.

Evolutionary Biology

Phenotypic Convergence in Bacterial Adaptive Evolution to Ethanol Stress

Bacterial cells have a remarkable ability to adapt and evolve to environmental changes, a phenomenon known as adaptive evolution. Adaptive evolution can be explained by phenotypic changes caused by genetic mutations, and by phenotypic plasticity that occur without genetic alteration, although far less is known about the contributions of the latter. In this study, we analyzed phenotypic and genotypic changes in Escherichia coli cells during adaptive evolution to ethanol stress. Phenotypic changes were quantified by transcriptome and metabolome analyses and found similar among independently evolved ethanol tolerant strains. The contribution of identified mutations in the tolerant strain was evaluated by using site-directed mutagenesis, which suggested that the fixation of these mutations cannot fully explain the observed ethanol tolerance. The phenotype of ethanol tolerance was stably maintained after an environmental change, suggesting that a mechanism of non-genetic memory contributed to at least part of the adaptation process.

Evolutionary Biology

Expansion load: recessive mutations and the role of standing genetic variation

Expanding populations incur a mutation burden - the so-called expansion load. Previous studies of expansion load have focused on co-dominant mutations. An important consequence of this assumption is that expansion load stems exclusively from the accumulation of new mutations occurring in individuals living at the wave front. Using individual-based simulations we study here the dynamics of standing genetic variation at the front of expansions, and its consequences on mean fitness if mutations are recessive. We find that deleterious genetic diversity is quickly lost at the front of the expansion, but the loss of deleterious mutations at some loci is compensated by an increase of their frequencies at other loci. The frequency of deleterious homozygotes therefore increases along the expansion axis whereas the average number of deleterious mutations per individual remains nearly constant across the species range. This reveals two important differences to co-dominant models: (i) mean fitness at the front of the expansion drops much faster if mutations are recessive, and (ii) mutation load can increase during the expansion even if the total number of deleterious mutations per individual remains constant. We use our model to make predictions about the shape of the site frequency spectrum at the front of range expansion, and about correlations between heterozygosity and fitness in different parts of the species range. Importantly, these predictions provide opportunities to empirically validate our theoretical results. We discuss our findings in the light of recent results on the distribution of deleterious genetic variation across human populations, and link them to empirical results on the correlation of heterozygosity and fitness found in many natural range expansions.

Evolutionary Biology

Strong selective sweeps on the X chromosome in the human-chimpanzee ancestor explain its low divergence

The human and chimpanzee X chromosomes are less divergent than expected based on autosomal divergence. This has led to a controversial hypothesis proposing a unique role of the X chromosome in human-chimpanzee speciation. We study incomplete lineage sorting patterns between humans, chimpanzees and gorillas to show that this low divergence is entirely due to megabase-sized regions comprising one-third of the X chromosome, where polymorphism in the human-chimpanzee ancestral species was severely reduced. Background selection can explain 10% of this reduction at most. Instead, we show that several strong selective sweeps in the ancestral species can explain this reduction of diversity in the ancestor. We also report evidence of population specific sweeps in extant humans that overlap the regions of low diversity in the ancestral species. These regions further correspond to chromosomal sections shown to be devoid of Neanderthal introgression into modern humans. This suggests that the same X-linked regions that undergo selective sweeps are among the first to form reproductive barriers between diverging species. We hypothesize that meiotic drive is the underlying mechanism causing these two observations.\n\nAuthors' SummaryBecause the speciation events that leads to human, chimpanzee and gorilla were close in time, their genetic relationship of these species varies along the genome. While human and chimpanzee species are most closely related, 15% of the human genome is more closely related to the gorilla genome than the chimpanzee genome, a phenomenon called incomplete lineage sorting (ILS). The amount and distribution of ILS can be predicted using population genetics theory, and is affected by demography and selection in the ancestral populations. It was previously reported that the X chromosome, in contrast to autosomes, is deprived of ILS, and this givies rise to controversial theories about the speciation event that splits humans and chimpanzees. Using a full genome alignment of the X chromosome, we show that this deprivation of ILS affects only one third of the chromosome. These regions also show reduced diversity in the extant populations of human and great apes, and coincide with regions devoid of Neanderthal introgression. We propose that these regions are targets of selection and that they played a role in the formation of reproductive barriers.

Evolutionary Biology