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SARS-CoV-2 is a newly discovered beta coronavirus at the end of 2019, which is highly pathogenic and poses a serious threat to human health. In this paper, 1,875 SARS-CoV-2 whole genome sequences and the sequence coding spike protein (S gene) sampled from the United States were used for the bioinformatics analysis to study the molecular evolutionary characteristics of its genome and spike protein. The MCMC method was used to calculate the evolution rate of the whole genome sequence and the nucleotide mutation rate of S gene. The results showed that the nucleotide mutation rate of the whole genome was 6.677×10-4 substitution per site per year, and the nucleotide mutation rate of S gene was 8.066×10-4 substitution per site per year, which was at a medium level compared with other RNA viruses. Our findings confirmed the scientific hypothesis that the rate of evolution of the virus gradually decreases over time. We also found 13 statistically significant positive selection sites in SARS-CoV-2 genome. In addition, the results showed that there were 101 non-synonymous mutation sites in the amino acid sequence of S protein, including seven putative harmful mutation sites. This paper preliminarily clarified the evolutionary characteristics of SARS-CoV-2 in the United States, providing a scientific basis for future surveillance and prevention of virus variants. This article is protected by copyright. All rights reserved.

Sex chromosomes contribute substantially to key evolutionary processes such as speciation and adaptation. Several theories suggest that evolution could occur more rapidly on sex chromosomes, but currently our understanding of whether and how this occurs is limited. Here, we present an analysis of the great tit (Parus major) genome, aiming to detect signals of faster-Z evolution. We find mixed evidence of faster divergence on the Z chromosome than autosomes, with significantly higher divergence being found in ancestral repeats, but not at 4- or 0-fold degenerate sites. Interestingly, some 4-fold sites appear to be selectively constrained, which may mislead analyses that use these sites as the neutral reference (e.g., dN/dS). Consistent with other studies in birds, the mutation rate is significantly higher in males than females, and the long-term Z-to-autosome effective population size ratio is only 0.5, significantly lower than the expected value of 0.75. These are indicative of male-driven evolution and high variance in male reproductive success, respectively. We find no evidence for an increased efficacy of positive selection on the Z chromosome. In contrast, the Z chromosome in great tits appears to be affected by increased genetic drift, which has led to detectable signals of weakened intensity of purifying selection. These results provide further evidence that the Z chromosome often has a low effective population size, and that this has important consequences for its evolution. They also highlight the importance of considering multiple factors that can affect the rate of evolution and effective population sizes of sex chromosomes.

The rate of mutations varies >100-fold across the genome, altering the rate of evolution, and susceptibility to genetic diseases. The strongest predictor of mutation rate is the sequence itself, varying 75-fold between trinucleotides. The fact that DNA sequence drives its own mutation rate raises a simple but important prediction; highly mutable sequences will mutate more frequently and eliminate themselves in favor of sequences with lower mutability, leading to a lower equilibrium mutation rate. However, purifying selection constrains changes in mutable sequences, causing higher rates of mutation. We conduct a simulation using real human mutation data to test if 1) DNA evolves to a low equilibrium mutation rate and 2) purifying selection causes a higher equilibrium mutation rate in the genome’s most important regions. We explore how this simple process affects sequence evolution in the genome, and discuss the implications for modeling evolution and susceptibility to DNA damage.

Proprotein convertases subtilisin kexins are serine endoproteases, playing critical roles in the biological functions, including lipid, glucose, and bile acid metabolism, as well as cell proliferation, migration, and metastasis. Experimental studies have demonstrated the physiological functions of PCSKs and their association with diseases; however, studies on the evolutionary history and diversification of these proteins are missing. In the present research, a bioinformatics study was conducted on the molecular evolution of several PCSKs family members and gene loss events across placental mammalian. In order to detect evolutionary constraints and positive selection, the CodeML program of the PAML package was used. The results showed the positive selection to occur in PCSK1, PCSK3, PCSK5, and PCSK7. A decelerated rate of evolution was observed in PCSK7, PCSK3, and MBTPS1 in Carnivores compared to the rest of phylogeny, and an accelerated evolution of PCSK1, PCSK7, and MBTPS1 in Muridae family of rodents was found. Additionally, our results indicated pcsk9 gene loss in 12 species comprising Carnivores and bats (Chiroptera). Future studies are required to evaluate the functional relevance and selective evolutionary advantages associated with these modifications in PCSK proteins during evolution.

Background 18S rRNA is a major component of the small subunit of the eukaryotic ribosome and an important phylogenetic marker for many groups, often to the point of being the only marker available for some. A core structure across eukaryotes exists for this molecule that can help to inform about its evolution in different groups. Using an alignment of 18S rDNA for Rotifera as traditionally recognized (=Bdelloidea, Monogononta, and Seisonacea, but not Acanthocephala), I fitted sequences for three exemplar species (Adineta vaga, Brachionus plicatilis, and Seison nebaliae, respectively) to the core structure and used these maps to reveal patterns of evolution for the remainder of this diverse group of microscopic animals. Results The obtained variability maps of the 18S rRNA molecule revealed a pattern of high diversity among the three major rotifer clades coupled with strong conservation within each of bdelloids and monogononts. A majority of individual sites (ca. 60%) were constant even across rotifers as a whole with variable sites showing only intermediate rates of evolution. Although the three structural maps each showed good agreement with the inferred core structure for eukaryotic 18S rRNA and so were highly similar to one another at the secondary and tertiary levels, the overall pattern is of three highly distinct, but conserved motifs within the group at the primary sequence level. A novel finding was that of a variably expressed deletion at the 3' end of the V3 hypervariable region among some bdelloid species that occasionally extended into and included the pseudoknot structure following this region as well as the central “square” of the 18S rRNA molecule. Compared to other groups, levels of variation and rates of evolution for 18S rRNA in Rotifera roughly matched those for Gastropoda and Acanthocephala, despite increasing evidence for the latter being a clade within Rotifera. Conclusions The lack of comparative data for comparable groups makes interpretation of the results (i.e., very low variation within each of the three major rotifer clades, but high variation between them) and their potential novelty difficult. However, these findings in combination with the high morphological diversity within rotifers potentially help to explain why no clear consensus has been reached to date with regard to the phylogenetic relationships among the major groups. Supplementary Information The online version contains supplementary material available at 10.1186/s12862-021-01845-2.

Most well-studied bacteria have been domesticated to some extent. How fast can a natural isolate diverge from its ancestral phenotypes under domestication to a novel laboratory environment is poorly known. Yet such information is key to understand rates of evolution, the time scale at which a natural isolate can be propagated without loss of its natural adaptive traits and the reliability of experimental results across labs. Using experimental evolution, phenotypic assays and whole-genome sequencing, we show that within a week of propagation in a common laboratory environment, a natural isolate ofBacillus subtilisacquires mutations that cause changes in a multitude of traits. A single adaptive mutational step, in the gene coding for the transcriptional regulator DegU, impairs a DegU-dependent positive autoregulatory loop and leads to loss of robust biofilm architecture, impaired swarming motility, reduced secretion of exoproteases and changes in the dynamics of sporulation across environments. Importantly, domestication also resulted in improved survival when the bacteria face pressure from cells of the innate immune system. These results show thatdegUis a key target for mutations during domestication and also underscore the importance of performing careful and extremely short-term propagations of natural isolates to conserve the traits encoded in their original genomes.SummaryDomestication is the process by which organisms are selected to live in specific conditions and an important phenomenon that shapes the evolution and variation in many animals and plants. In microbes, domestication is also a key driver of adaptation. It can be beneficial, when improving microbes abilities that are important for biotechnology, but also problematic, especially when studying microbe-host interactions and the microbe’s natural behavior. Using a natural isolate ofBacillus subtilis, we determined the speed and genetic basis of microbial domestication using experimental evolution. Within one week of growth in the common laboratory media, mutations in the pleiotropic transcriptional regulator, DegU, emerge and spread in the populations. These lead to loss of social traits, increased resistance to bacteriophages and increased survival in the presence of macrophages. The data highlights the extreme caution that is needed when culturing natural microbial isolates and may help explain why some key microbial social traits and behaviors may differ between different laboratories, even when studying the same strains.

The mammalian CIP/KIP family proteins are intrinsically disordered proteins (IDPs) that can regulate various cellular processes. However, many reports have shown that IDPs generally evolve more rapidly than ordered proteins. Here, to elucidate the functional adaptability of CIP/KIP proteins in vertebrate, we analysed the rates of evolution in relation to their structural and sequence properties and predicted the post-translational modification based on the sequence data. The results showed that CIP/KIP proteins generally could maintain their function through evolution in the vertebrate. Basically, the disordered region that acts as a flexible linker or spacer has a conserved propensity for structural disorder and a persistent, fast rate of amino acid substitution, which could result in a significantly faster rate of evolution compared to the ordered proteins. Describing the pattern of structural order-disorder evolution, this study may give an insight into the well-known characteristics of IDPs in the evolution of CIP/KIP proteins.

The rate of evolution varies among sites within proteins. In enzymes, two rate gradients are observed: rate decreases with increasing local packing and it increases with increasing distance from catalytic residues. The rate-packing gradient would be mainly due to stability constraints and is well reproduced by biophysical models with selection for protein stability. However, stability constraints are unlikely to account for the rate-distance gradient. Here, to explore the mechanistic underpinnings of the rate gradients observed in enzymes, I propose a stability-activity model of enzyme evolution, MSA. This model is based on a two-dimensional fitness function that depends on stability, quantified by Î "G, the enzyme's folding free energy, and activity, quantified by Î "G∗, the activation energy barrier of the enzymatic reaction. I test MSA on a diverse data set of enzymes, comparing it with two simpler models: MS, which depends only on Î "G, and MA, which depends only on Î "G∗. I found that MSA clearly outperforms both MS and MA and it accounts for both the rate-packing and rate-distance gradients. Thus, MSA captures the distribution of stability and activity constraints within enzymes, explaining the resulting patterns of rate variation among sites. Fil: Echave, Julián. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Inconsistent results on the association between evolutionary rates and amino acid composition of proteins have been reported in eukaryotes. However, there are few studies of how amino acid composition can influence evolutionary rates in bacteria. Thus, we constructed linear regression models between composition frequencies of amino acids and evolutionary rates for bacteria. Compositions of all amino acids can on average explain 21.5% of the variation in evolutionary rates among 273 investigated bacterial organisms. In five model organisms, amino acid composition contributes more to variation in evolutionary rates than protein abundance, and frequency of optimal codons. The contribution of individual amino acid composition to evolutionary rate varies among organisms. The closer the GC-content of genome to its maximum or minimum, the better the correlation between the amino acid content and the evolutionary rate of proteins would appear in that genome. The types of amino acids that significantly contribute to evolutionary rates can be grouped into GC-rich and AT-rich amino acids. Besides, the amino acid with high composition also contributes more to evolutionary rates than amino acid with low composition in proteome. In summary, amino acid composition significantly contributes to the rate of evolution in bacterial organisms and this in turn is impacted by GC-content.

The POU1F1 (Pit-1) transcription factor is important in regulating expression of growth hormone, prolactin and TSH β-subunit, and controlling development of the anterior pituitary cells in which these hormones are produced. POU1F1 is a conserved protein comprising three main domains, an N-terminal transcription activation domain (TAD), a POU-specific domain and a C-terminal homeodomain. Within the TAD, a β-domain can be inserted by alternative splicing, giving an extended 'β-variant' with altered properties. Here sequence data from over 100 species were used to assess the variability of POU1F1 in mammals. This showed that the POU-specific domain and homeodomain are very strongly conserved, and that the TAD is somewhat less conserved, as are linker and hinge regions between these main domains. On the other hand, the β-domain is very variable, apparently evolving at a rate not significantly different from that expected for unconstrained, neutral evolution. In several species stop and/or frameshift mutations within the β domain would prevent expression of the β-variant as a functional protein. In most species expression of the β-variant is low (

Zika virus (ZIKV) is a member of the family Flaviviridae. ZIKV emerged in Brazil in 2015, causing an unprecedented epidemic and since then the virus has rapidly spread throughout the Americas. These facts highlight the need of detailed phylogenetic studies to understand the emergence, spread and evolution of ZIKV populations. For these reasons, a Bayesian coalescent Markov Chain Monte Carlo analysis of complete genome sequences of ZIKV strains recently isolated in the American continent was performed. The results of these studies revealed an increasing diversification of ZIKV strains in different genetic lineages and co-circulation of distinct genetic lineages in several countries in the region. The time of the most recent common ancestor (tMRCA) was established to be around February 20th, 2014 for ZIKV strains circulating in the American region. A mean rate of evolution of 1.55 × 10−3 substitutions/site/year was obtained for ZIKV strains included in this study. A Bayesian skyline plot indicate a sharp increase in population size from February, 2014 to July 2015 and a decline during 2016. These results are discussed in terms of the emergence and evolution of ZIKV populations in the American continent. This article is protected by copyright. All rights reserved

The story of how preColumbian civilizations developed goes hand-in-hand with the process of plant domestication by Mesoamerican inhabitants. Here, we present the almost complete sequence of a mitochondrial genome and a partial chloroplast genome from an archaeological maize sample collected at the Valley of Tehuacan, Mexico. Accelerator mass spectrometry dated the maize sample to be 5,040-5,300 years before present (95% probability). Phylogenetic analysis of the mitochondrial genome shows that the archaeological sample branches basal to the other Zea mays genomes, as expected. However, this analysis also indicates that fertile genotype NB is closely related to the archaeological maize sample and evolved before cytoplasmic male sterility genotypes (CMS-S, CMS-T, and CMS-C), thus contradicting previous phylogenetic analysis of mitochondrial genomes from maize. We show that maximum-likelihood infers a tree where CMS genotypes branch at the base of the tree when including sites that have a relative fast rate of evolution thus suggesting long-branch attraction. We also show that Bayesian analysis infer a topology where NB and the archaeological maize sample are at the base of the tree even when including faster sites. We therefore suggest that previous trees suffered from long-branch attraction. We also show that the phylogenetic analysis of the ancient chloroplast is congruent with genotype NB to be more closely related to the archaeological maize sample. As shown here, the inclusion of ancient genomes on phylogenetic trees greatly improves our understanding of the domestication process of maize, one of the most important crops worldwide.

Background On January 30th, 2020, an outbreak of atypical pneumonia caused by a novel Betacoronavirus (βCoV), named SARS‐CoV‐2, was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS‐CoV‐2 strains currently circulating in different geographic regions of the world was performed. Methods A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS‐CoV‐2 strains recently isolated in Europe, North America, South America and Asia was performed. Results The results of these studies revealed a diversification of SARS‐CoV‐2 strains in three different genetic clades. Co‐circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor (tMRCA) was established to be around November 1, 2019. A mean rate of evolution of 6.57 x 10‐4 substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. Conclusion The results of these studies revealed an increasing diversification of SARS‐CoV‐2 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS‐CoV‐2 strains. This article is protected by copyright. All rights reserved.

The rate of evolution of viral genomes is a fundamental parameter for understanding the origin and spread of epidemics. For instance, molecular dating is one of the many practical outcomes of evolutionary rate estimation. In this sense, the rate of evolution of ZIKV merits attention, because it has been shown to be higher than the average rate reported for other flaviviruses. It has been hypothesized that the higher rate of ZIKV evolution is due to a bias related to the analysis of sequences collected within a short time range, which would increase the chance of sampling slightly deleterious nucleotide polymorphisms. To investigate this hypothesis, we assembled datasets with different ranges of sampling times and also decomposed the ZIKV evolutionary rate into synonymous and non-synonymous rates. Our results demonstrated that the rate of ZIKV evolution is time dependent and that the observed increase in short-term rates is largely accounted for by a higher non-synonymous rate, suggesting the presence of slightly deleterious variants not yet eliminated by purifying selection. On the other hand, we show that synonymous rates were less impacted by the range of sampling times, generating timescales with reduced uncertainty. We conclude that, for inferring the ZIKV timescale and reconstructing the history of epidemics, synonymous changes are the most appropriate substitution type to be examined. We were able to obtain ZIKV divergence times that were time independent and exhibited greater precision than previous estimates. This observation should also hold for other serially sampled fast-evolving pathogens with evidence of time dependence of evolutionary rates.

HIV-1 is a fast-evolving, genetically diverse virus presently classified into several groups and subtypes. The virus evolves rapidly because of an error-prone polymerase, high rates of recombination, and selection in response to the host immune system and clinical management of the infection. The rate of evolution is also influenced by the rate of virus spread in a population and nature of the outbreak, among other factors. HIV-1 evolution is thus driven by a range of complex genetic, social, and epidemiological factors that complicates disease management and prevention. Here, we quantify the evolutionary (substitution) rate heterogeneity among major HIV-1 subtypes and recombinants by analyzing the largest collection of HIV-1 genetic data spanning the widest possible geographical (100 countries) and temporal (1981–2019) spread. We show that HIV-1 substitution rates vary substantially, sometimes by several folds, both across the virus genome and between major subtypes and recombinants, but also within a subtype. Across subtypes, rates ranged 3.5-fold from 1.34 × 10−3 to 4.72 × 10−3 in env and 2.3-fold from 0.95 × 10−3 to 2.18 × 10−3 substitutions site−1 year−1 in pol. Within the subtype, 3-fold rate variation was observed in env in different human populations. It is possible that HIV-1 lineages in different parts of the world are operating under different selection pressures leading to substantial rate heterogeneity within and between subtypes. We further highlight how such rate heterogeneity can complicate HIV-1 phylodynamic studies, specifically, inferences on epidemiological linkage of transmission clusters based on genetic distance or phylogenetic data, and can mislead estimates about the timing of HIV-1 lineages.

The molecular clock hypothesis is an important concept in biology. Deviations from a constant rate of nucleotide substitution have been found widely among lineages, genomes, genes and individual sites. Phylogenetic research can accommodate for these differences in applying specific models of evolution. Lineage-specific rate heterogeneity however can generate bi- or multimodal distributions of substitution rates across the branches of a tree and this may mislead phylogenetic inferences with currently available models. The plant family Annonaceae is an excellent case to study lineage-specific rate heterogeneity. The two major sister subfamilies, Annonoideae and Malmeoideae, have shown great discrepancies in branch lengths. We used high-throughput sequencing data of 72 genes, 99 spacers and 16 introns from 24 chloroplast genomes and nuclear ribosomal DNA of 23 species to study the molecular rate of evolution in Annonaceae. In all analyses, longer branch lengths and/or higher substitution rates were found for the Annonoideae compared to the Malmeoideae. The Annonaceae had wide variability in chloroplast length, ranging from minimal 175,684 by to 201,723 for Annonoideae and minimal 152,357 to 170,985 bp in Malmeoideae, mostly reflecting variation in inverted-repeat length. The Annonoideae showed a higher GC-content in the conserved parts of the chloroplast genome and higher omega (dN/c/s)-ratios than the Malmeoideae, which could indicate less stringent purifying selection, a pattern that has been found in groups with small population sizes. This study generates new insights into the processes causing lineage-specific rate heterogeneity, which could lead to improved phylogenetic methods. (C) 2017 Elsevier Inc. All rights reserved.

Contrary to classical population genetics theory, experiments demonstrate that fluctuating selection can protect a haploid polymorphism in the absence of frequency dependent effects on fitness. Using forward simulations with the Moran model, we confirm our analytical results showing that a fluctuating selection regime, with a mean selection coefficient of zero, promotes polymorphism. We find that increases in heterozygosity over neutral expectations are especially pronounced when fluctuations are rapid, mutation is weak, the population size is large, and the variance in selection is big. Lowering the frequency of fluctuations makes selection more directional, and so heterozygosity declines. We also show that fluctuating selection raises dn/ds ratios for polymorphism, not only by sweeping selected alleles into the population, but also by purging the neutral variants of selected alleles as they undergo repeated bottlenecks. Our analysis shows that randomly fluctuating selection increases the rate of evolution by increasing the probability of fixation. The impact is especially noticeable when the selection is strong and mutation is weak. Simulations show the increase in the rate of evolution declines as the rate of new mutations entering the population increases, an effect attributable to clonal interference. Intriguingly, fluctuating selection increases the dn/ds ratios for divergence more than for polymorphism, a pattern commonly seen in comparative genomics. Our model, which extends the classical neutral model of molecular evolution by incorporating random fluctuations in selection, accommodates a wide variety of observations, both neutral and selected, with economy.

Influenza viruses evolve at such a high rate that vaccine recommendations need to be changed, but not quite on a regular basis. This observation suggests that the rate of evolution of these viruses is not constant through time, which begs the question as to when such rate changes occur, if they do so independently of the host in which they circulate and (or) independently of their subtype. To address these outstanding questions, we introduce a novel heuristics, Mclust*, that is based on a two-tier clustering approach in a phylogenetic context to estimate (i) absolute rates of evolution and (ii) when rate change occurs. We employ the novel approach to compare the two influenza surface proteins, hemagglutinin and neuraminidase, that circulated in avian, human, and swine hosts between 1960 and 2014 in two subtypes: H3N2 and H1N1. We show that the algorithm performs well in most conditions, accounting for phylogenetic uncertainty by means of bootstrapping and scales up to analyze very large data sets. Our results show that our approach is robust to the time-dependent artifact of rate estimation, and confirm pervasive punctuated evolution across hosts and subtypes. As such, the novel approach can potentially detect when vaccine composition needs to be updated.

Nonsense mutations turn a coding (sense) codon into an in-frame stop codon that is assumed to result in a truncated protein product. Thus, nonsense substitutions are the hallmark of pseudogenes and are used to identify them. Here we show that in-frame stop codons within bacterial protein-coding genes are widespread. Their evolutionary conservation suggests that many of them are not pseudogenes, since they maintain dN/dS values (ratios of substitution rates at non-synonymous and synonymous sites) significantly lower than 1 (this is a signature of purifying selection in protein-coding regions). We also found that double substitutions in codons—where an intermediate step is a nonsense substitution—show a higher rate of evolution compared to null models, indicating that a stop codon was introduced and then changed back to sense via positive selection. This further supports the notion that nonsense substitutions in bacteria are relatively common and do not necessarily cause pseudogenization. In-frame stop codons may be an important mechanism of regulation: Such codons are likely to cause a substantial decrease of protein expression levels.

The rate of evolution differs between protein sites and changes with time. However, the link between these two phenomena remains poorly understood. Here, we design a phylogenetic approach for distinguishing pairs of amino acid sites that evolve concordantly, i.e., such that substitutions at one site trigger subsequent substitutions at the other; and also pairs of sites that evolve discordantly, so that substitutions at one site impede subsequent substitutions at the other. We distinguish groups of amino acid sites that undergo coordinated evolution and evolve discordantly from other such groups. In mitochondrion-encoded proteins of metazoans and fungi, we show that concordantly evolving sites are clustered in protein structures. By analysing the phylogenetic patterns of substitutions at concordantly and discordantly evolving site pairs, we find that concordant evolution has two distinct causes: epistatic interactions between amino acid substitutions and episodes of selection independently affecting substitutions at different sites. The rate of substitutions at concordantly evolving groups of protein sites changes in the course of evolution, indicating episodes of selection limited to some of the lineages. The phylogenetic positions of these changes are consistent between proteins, suggesting common selective forces underlying them., Author summary The mode and rate of evolution of a protein site depends on the effect of its mutations on protein fitness. The fitness effect of a mutation itself can change in the course of evolution for at least two reasons. First, it can be modulated by substitutions occurring at other sites, a phenomenon called epistasis. Second, changes in selection can be non-epistatic, affecting sites independently of one another. Here, we analyse substitutions accumulated by the evolving lineages of the five proteins encoded by the mitochondrial genomes of thousands of species of metazoans and fungi. We show that substitutions at different amino acid sites occur in a coordinated fashion, and this coordination is caused both by epistasis and by episodes of selection affecting groups of sites. We partition each protein into several groups of concordantly evolving sites such that evolution of sites from different groups is discordant, and show that the proteins encoded by the mitochondrial genome consist of coevolving structural blocks. Some of these blocks have a clear functional specialization, e.g. are associated with interfaces between proteins composing respiratory complexes. Together, our results reveal a previously unrecognized complexity in the causes of variation in evolutionary rates between protein sites.

Protein stability is a major constraint on protein evolution. Molecular chaperones, also known as heat-shock proteins, can relax this constraint and promote protein evolution by diminishing the deleterious effect of mutations on protein stability and folding. This effect, however, has only been stablished for a few chaperones. Here, we use a comprehensive chaperone-protein interaction network to study the effect of all yeast chaperones on the evolution of their protein substrates, that is, their clients. In particular, we analyze how yeast chaperones affect the evolutionary rates of their clients at two very different evolutionary time scales. We first study the effect of chaperone-mediated folding on protein evolution over the evolutionary divergence ofSaccharomyces cerevisiaeandS. paradoxus. We then test whether yeast chaperones have left a similar signature on the patterns of standing genetic variation found in modern wild and domesticated strains ofS. cerevisiae. We find that genes encoding chaperone clients have diverged faster than genes encoding nonclient proteins when controlling for their number of protein-protein interactions. We also find that genes encoding client proteins have accumulated more intra-specific genetic diversity than those encoding nonclient proteins. In a number of multivariate analyses, controlling by other well-known factors that affect protein evolution, we find that chaperone dependence explains the largest fraction of the observed variance in the rate of evolution at both evolutionary time scales. Chaperones affecting rates of protein evolution mostly belong to two major chaperone families: Hsp70s and Hsp90s. Our analyses show that protein chaperones, by virtue of their ability to buffer destabilizing mutations and their role in modulating protein genotype-phenotype maps, have a considerable accelerating effect on protein evolution.

Background Members of different sections of the genus Linum are characterized by wide variability in size, morphology and number of chromosomes in karyotypes. Since such variability is determined mainly by the amount and composition of repeated sequences, we conducted a comparative study of the repeatomes of species from four sections forming a clade of blue-flowered flax. Based on the results of high-throughput genome sequencing performed in this study as well as available WGS data, bioinformatic analyses of repeated sequences from 12 flax samples were carried out using a graph-based clustering method. Results It was found that the genomes of closely related species, which have a similar karyotype structure, are also similar in the repeatome composition. In contrast, the repeatomes of karyologically distinct species differed significantly, and no similar tandem-organized repeats have been identified in their genomes. At the same time, many common mobile element families have been identified in genomes of all species, among them, Athila Ty3/gypsy LTR retrotransposon was the most abundant. The 30-chromosome members of the sect. Linum (including the cultivated species L. usitatissimum) differed significantly from other studied species by a great number of satellite DNA families as well as their relative content in genomes. Conclusions The evolution of studied flax species was accompanied by waves of amplification of satellite DNAs and LTR retrotransposons. The observed inverse correlation between the total contents of dispersed repeats and satellite DNAs allowed to suggest a relationship between both classes of repeating sequences. Significant interspecific differences in satellite DNA sets indicated a high rate of evolution of this genomic fraction. The phylogenetic relationships between the investigated flax species, obtained by comparison of the repeatomes, agreed with the results of previous molecular phylogenetic studies.

The molecular clock and its phylogenetic applications to genomic data have changed how we study and understand one of the major human pathogens, Mycobacterium tuberculosis (MTB), the etiologic agent of tuberculosis. Genome sequences of MTB strains sampled at different times are increasingly used to infer when a particular outbreak begun, when a drug-resistant clone appeared and expanded, or when a strain was introduced into a specific region. Despite the growing importance of the molecular clock in tuberculosis research, there is a lack of consensus as to whether MTB displays a clocklike behavior and about its rate of evolution. Here we performed a systematic study of the molecular clock of MTB on a large genomic data set (6,285 strains), covering different epidemiological settings and most of the known global diversity. We found that sampling times below 15–20 years were often insufficient to calibrate the clock of MTB. For data sets where such calibration was possible, we obtained a clock rate between 1x10-8 and 5x10-7 nucleotide changes per-site-per-year (0.04–2.2 SNPs per-genome-per-year), with substantial differences between clades. These estimates were not strongly dependent on the time of the calibration points as they changed only marginally when we used epidemiological isolates (sampled in the last 40 years) or three ancient DNA samples (about 1,000 years old) to calibrate the tree. Additionally, the uncertainty and the discrepancies in the results of different methods were sometimes large, highlighting the importance of using different methods, and of considering carefully their assumptions and limitations., Author summary One of the major recent advancements in evolutionary biology is the development of statistical methods to infer the past evolutionary history of species and populations with genomic data. In the last five years, many researchers have used the molecular clock (i.e. the observation that genomes accumulate mutations at an approximately constant pace) to study the evolution and epidemiology of Mycobacterium tuberculosis, a bacterial pathogen that causes tuberculosis and is responsible for 1.6 million human deaths ever year. Applications of the molecular clock are used to understand when tuberculosis emerged as a pathogen, the evolution of drug resistance, how different strains transmit and spread across the world and how MTB populations are affected by control programs. Here, we performed a systematic analysis of the molecular clock of MTB, analyzing several whole genome sequence data sets with the same set of methodologies. We characterized the rate of molecular evolution (the pace of the clock), and its variation between different MTB populations and lineages. Our results provide an important guideline for future analyses of tuberculosis and other organisms.

The genetic variation of our species reflects human demographic history and adaptation to diverse local environments. Part of this genetic variation affects individual responses to exogenous substances, such as food, pollutants and drugs, and plays an important role in drug efficacy and safety. This review provides a synthesis of the evolution of loci implicated in human pharmacological response and metabolism, interpreted within the theoretical framework of population genetics and molecular evolution. In particular, I review and discuss key evolutionary aspects of different pharmacogenes in humans and other species, such as the relationship between the type of substrates and rate of evolution; the selective pressure exerted by landscape variables or dietary habits; expected and observed patterns of rare genetic variation. Finally, I discuss how this knowledge can be translated directly or after the implementation of specific studies, into practical guidelines.

International audience; Next generation sequencing (NGS) and genomic database mining allow biologists to gather and select large molecular datasets well suited to address phylogenomics and molecular evolution questions. Here we applied this approach to a mammal family, the Echimyidae, for which generic relationships have been difficult to recover and often referred to as a star phylogeny. These South-American spiny rats represent a family of caviomorph rodents exhibiting a striking diversity of species and life history traits. Using a NGS exon capture protocol, we isolated and sequenced ca. 500 nuclear DNA exons for 35 species belonging to all major echimyid and capromyid clades. Exons were carefully selected to encompass as much diversity as possible in terms of rate of evolution, heterogeneity in the distribution of site-variation and nucleotide composition. Supermatrix inferences and coalescence-based approaches were subsequently applied to infer this family’s phylogeny. The inferred topologies were the same for both approaches, and support was maximal for each node, entirely resolving the ambiguous relationships of previous analyses. Fast-evolving nuclear exons tended to yield more reliable phylogenies, as slower-evolving sequences were not informative enough to disentangle the short branches of the Echimyidae radiation. Based on this resolved phylogeny and on molecular and morphological evidence, we confirm the rank of the Caribbean hutias – formerly placed in the Capromyidae family – as Capromyinae, a clade nested within Echimyidae. We also name and define Carterodontinae, a new subfamily of Echimyidae, comprising the extant monotypic genus Carterodon from Brazil, which is the closest living relative of West Indies Capromyinae.

The amount of plastome sequence data available has soared in the last decade, but the nature of plastome evolution during rapid radiations is largely unknown. Moreover, although there is increasing evidence showing that plastomes may have undergone adaptive evolution in order to allow adaptation to various environments, few studies have systematically investigated the role of the plastome in alpine adaptation. To address these questions, we sequenced and analyzed 12 representative species of Rhodiola, a genus which includes ca. 70 perennial herbs mainly growing in alpine habitats in the Qinghai-Tibet Plateau and the Hengduan Mountains. Rapid radiation in this genus was triggered by the uplift of the Qinghai-Tibet Plateau. We also included nine species of Crassulaceae as the outgroups. All plastomes were conserved with respect to size, structure, and gene content and order, with few variations: each contained 134 genes, including 85 protein-coding genes, 37 tRNAs, 8 rRNAs, and 4 potential pseudogenes. Four types of repeat sequence were detected. Slight contraction and expansion of the inverted repeats were also revealed. Both the genome-wide alignment and sequence polymorphism analyses showed that the inverted repeats and coding regions were more conserved than the single-copy regions and the non-coding regions. Positive selection analyses identified three genes containing sites of positive selection (rpl16, ndhA, ndhH), and one gene with a faster than average rate of evolution (psaA). The products of these genes may be involved in the adaptation of Rhodiola to alpine environments such as low CO2 concentration and high-intensity light.

Five decades have passed since the proposal of the molecular clock hypothesis,which states that the rate of evolution at the molecular level is constant through time and among species. This hypothesis has become a powerful tool in evolutionary biology, making it possible to use molecular sequences to estimate the geological ages of species divergence events. With recent advances in Bayesian clock dating methodology and the explosive accumulation of genetic sequence data, molecular clock dating has found widespread applications, from tracking virus pandemics and studying the macroevolutionary process of speciation and extinction to estimating a timescale for life on Earth

The germline mutation rate is an important parameter that affects the amount of genetic variation and the rate of evolution. However, neither the rate of germline mutations in laboratory mice nor the biological significance of the mutation rate in mammalian populations is clear. Here we studied genome-wide mutation rates and the long-term effects of mutation accumulation on phenotype in more than 20 generations of wild-type C57BL/6 mice and mutator mice, which have high DNA replication error rates. We estimated the base-substitution mutation rate to be 5.4 × 10−9 (95% confidence interval = 4.6 × 10−9–6.5 × 10−9) per nucleotide per generation in C57BL/6 laboratory mice, about half the rate reported in humans. The mutation rate in mutator mice was 17 times that in wild-type mice. Abnormal phenotypes were 4.1-fold more frequent in the mutator lines than in the wild-type lines. After several generations, the mutator mice reproduced at substantially lower rates than the controls, exhibiting low pregnancy rates, lower survival rates, and smaller litter sizes, and many of the breeding lines died out. These results provide fundamental information about mouse genetics and reveal the impact of germline mutation rates on phenotypes in a mammalian population.

The difference between rapid morphological evolutionary changes observed in populations and the long periods of stasis detected in the fossil record has raised a decade-long debate about the exact role played by intraspecific mechanisms at the interspecific level. Although they represent different scales of the same evolutionary process, micro- and macroevolution are rarely studied together and few empirical studies have compared the rates of evolution and the selective pressures between both scales. Here, we analyse morphological, genetic and ecological traits in clownfishes at different evolutionary scales and demonstrate that the tempo of molecular and morphological evolution at the species level can be, to some extent, predicted from parameters estimated below the species level, such as the effective population size or the rate of evolution within populations. We also show that similar codons in the gene of the rhodopsinRH1, a light-sensitive receptor protein, are under positive selection at the intra and interspecific scales, suggesting that similar selective pressures are acting at both levels.

Premise of the study Leaf surface traits, such as trichome density and wax production, mediate important ecological processes such as anti-herbivory defense and water-use efficiency. We present a phylogenetic analysis of Asclepias plastomes as a framework for analyzing the evolution of trichome density and presence of epicuticular waxes. Methods We produced a maximum-likelihood phylogeny using plastomes of 103 species of Asclepias. We reconstructed ancestral states and used model comparisons in a likelihood framework to analyze character evolution across Asclepias. Key results We resolved the backbone of Asclepias, placing the Sonoran Desert clade and Incarnatae clade as successive sisters to the remaining species. We present novel findings about leaf surface evolution of Asclepias-the ancestor is reconstructed as waxless and sparsely hairy, a macroevolutionary optimal trichome density is supported, and the rate of evolution of trichome density has accelerated. Conclusions Increased sampling and selection of best-fitting models of evolution provide more resolved and robust estimates of phylogeny and character evolution than obtained in previous studies. Evolutionary inferences are more sensitive to character coding than model selection.

We give a non-technical introduction to convergence–divergence models, a new modeling approach for phylogenetic data that allows for the usual divergence of lineages after lineage-splitting but also allows for taxa to converge, i.e. become more similar over time. By examining the [Formula: see text]-taxon case in some detail, we illustrate that phylogeneticists have been “spoiled” in the sense of not having to think about the structural parameters in their models by virtue of the strong assumption that evolution is tree-like. We show that there are not always good statistical reasons to prefer the usual class of tree-like models over more general convergence–divergence models. Specifically, we show many [Formula: see text]-taxon data sets can be equally well explained by supposing violation of the molecular clock due to change in the rate of evolution along different edges, or by keeping the assumption of a constant rate of evolution but instead assuming that evolution is not a purely divergent process. Given the abundance of evidence that evolution is not strictly tree-like, our discussion is an illustration that as phylogeneticists we need to think clearly about the structural form of the models we use. For cases with four taxa, we show that there will be far greater ability to distinguish models with convergence from non-clock-like tree models. [Akaike information criterion; convergence–divergence models; distinguishability; identifiability; likelihood; molecular clock; phylogeny.]

Origin of new biological functions is a complex phenomenon ranging from single-nucleotide substitutions to the gain of new genes via horizontal gene transfer or duplication. Neofunctionalization and subfunctionalization of proteins is often attributed to the emergence of paralogs that are subject to relaxed purifying selection or positive selection and thus evolve at accelerated rates. Such phenomena potentially could be detected as anomalies in the phylogenies of the respective gene families. We developed a computational pipeline to search for such anomalies in 1,834 orthologous clusters of archaeal genes, focusing on lineage-specific subfamilies that significantly deviate from the expected rate of evolution. Multiple potential cases of neofunctionalization and subfunctionalization were identified, including some ancient, house-keeping gene families, such as ribosomal protein S10, general transcription factor TFIIB and chaperone Hsp20. As expected, many cases of apparent acceleration of evolution are associated with lineage-specific gene duplication. On other occasions, long branches in phylogenetic trees correspond to horizontal gene transfer across long evolutionary distances. Significant deceleration of evolution is less common than acceleration, and the underlying causes are not well understood; functional shifts accompanied by increased constraints could be involved. Many gene families appear to be “highly evolvable,” that is, include both long and short branches. Even in the absence of precise functional predictions, this approach allows one to select targets for experimentation in search of new biology.

Sex chromosomes evolve differently from autosomes because natural selection acts distinctly on them given their reduced recombination and smaller population size. Various studies of sex-linked genes compared with different autosomal genes within species support these predictions. Here, we take a novel alternative approach by comparing the rate of evolution between subsets of genes that are sex-linked in selected reptiles/vertebrates and the same genes located in autosomes in other amniotes. We report for the first time the faster evolution of Z-linked genes in a turtle (the Chinese softshell turtle Pelodiscus sinensis) relative to autosomal orthologs in other taxa, including turtles with temperature-dependent sex determination (TSD). This faster rate was absent in its close relative, the spiny softshell turtle (Apalone spinifera), thus revealing important lineage effects, and was only surpassed by mammalian-X linked genes. In contrast, we found slower evolution of X-linked genes in the musk turtle Staurotypus triporcatus (XX/XY) and homologous Z-linked chicken genes. TSD lineages displayed overall faster sequence evolution than taxa with genotypic sex determination (GSD), ruling out global effects of GSD on molecular evolution beyond those by sex-linkage. Notably, results revealed a putative selective sweep around two turtle genes involved in vertebrate gonadogenesis (Pelodiscus-Z-linked Nf2 and Chrysemys-autosomal Tspan7). Our observations reveal important evolutionary changes at the gene level mediated by chromosomal context in turtles despite their low overall evolutionary rate and illuminate sex chromosome evolution by empirically testing expectations from theoretical models. Genome-wide analyses are warranted to test the generality and prevalence of the observed patterns.

For decades, rates of protein evolution have been interpreted in terms of the vague concept of “functional importance”. Slowly evolving proteins or sites within proteins were assumed to be more functionally important and thus subject to stronger selection pressure. More recently, biophysical models of protein evolution, which combine evolutionary theory with protein biophysics, have completely revolutionized our view of the forces that shape sequence divergence. Slowly evolving proteins have been found to evolve slowly because of selection against toxic mis-folding and misinteractions, linking their rate of evolution primarily to their abundance. Similarly, most slowly evolving sites in proteins are not directly involved in function, but mutating them has large impacts on protein structure and stability. Here, we review the studies of the emergent field of biophysical protein evolution that have shaped our current understanding of sequence divergence patterns. We also propose future research directions to develop this nascent field.

Autophagy is the cellular process of removal of misfolded or damaged macromolecules and organelles. Experimental studies have demonstrated autophagy as a major mechanism of lifespan extension in long-lived mammals such as bats and mole rat rodents. Moreover, the role of this biological process has been well documented in protection against age-associated diseases and viral infection. However, studies on the molecular adaptive changes of autophagy factors during evolution are scarce. Here, we conducted a bioinformatics study of the molecular evolution of the Lysosomal Associated Membrane Protein 2 (LAMP2), as a rate-limiting factor in the lysosomal degradation stage of autophagy (the communal step of two of autophagy types: macroautophagy and chaperone-mediated). Analyzing LAMP2 across placental mammals, our phylogenetic-based maximum likelihood analyses indicate that the majority of the coding sites undergo purifying selection. However, around 27% of sites display a relaxation of purifying constraints (average ω = 0.42128), among which, 14 particular sites undergo positive selection (ω > 1). These sites are mostly located in the first luminal domain of LAMP2 (N-domain), with a hotspot region in the 135–144 codons interval. Therefore, the N-domain may account for the functional diversity and regulation of LAMP2. In addition, the identified positive selection sites could act as key regulatory sites in the LAMP2 function. On the other hand, testing the rate of evolution in LAMP2 along different clades of placental mammals revealed a relatively relaxed evolution in LAMP2 along megabats’ clade. It is not clear yet whether an expedited evolution of LAMP2 in megabats has contributed to their reported up-regulation of autophagy. Finally, our data indicate positive selection sites along the ancestral branch of the clades of rodents, mouse-related rodents, and mole-rats; and suggest the potentially important regulatory role of these sites in LAMP2. Identifying the residues under positive selection, our findings pave the way for future experimental investigations to define how these selective substitutions have functionally affected autophagy.

There are two strong and equally important predictors of rates of human protein evolution: The amount the gene is expressed and the proportion of exonic sequence devoted to control splicing, mediated largely by selection on exonic splice enhancer (ESE) motifs. Is the same true for noncoding RNAs, known to be under very weak purifying selection? Prior evidence suggests that selection at splice sites in long intergenic noncoding RNAs (lincRNAs) is important. We now report multiple lines of evidence indicating that the great majority of purifying selection operating on lincRNAs in humans is splice related. Splice-related parameters explain much of the between-gene variation in evolutionary rate in humans. Expression rate is not a relevant predictor, although expression breadth is weakly so. In contrast to protein-coding RNAs, we observe no relationship between evolutionary rate and lincRNA stability. As in protein-coding genes, ESEs are especially abundant near splice junctions and evolve slower than non-ESE sequence equidistant from boundaries. Nearly all constraint in lincRNAs is at exon ends (N.B. the same is not witnessed in Drosophila). Although we cannot definitely answer the question as to why splice-related selection is so important, we find no evidence that splicing might enable the nonsense-mediated decay pathway to capture transcripts incorrectly processed by ribosomes. We find evidence consistent with the notion that splicing modifies the underlying chromatin through recruitment of splice-coupled chromatin modifiers, such as CHD1, which in turn might modulate neighbor gene activity. We conclude that most selection on human lincRNAs is splice mediated and suggest that the possibility of splice–chromatin coupling is worthy of further scrutiny.

Complex traits arise from the interactions among multiple gene products. In the case where the complex phenotype is separated from the wild type by a fitness valley or a fitness plateau, the generation of a complex phenotype may take a very long evolutionary time. Interestingly, the rate of evolution depends in nontrivial ways on various properties of the underlying stochastic process, such as the spatial organization of the population and social interactions among cells. Here we review some of our recent work that investigates these phenomena in asexual populations. The role of spatial constraints is quite complex: there are realistic cases where spatial constrains can accelerate or delay evolution, or even influence it in a nonmonotonic fashion, where evolution works fastest for intermediate-range constraints. Social interactions among cells can be studied in the context of the division-of-labor games. Under a range of circumstances, cooperation among cells can lead to a relatively fast creation of a complex phenotype as an emerging (distributed) property. If we further assume the presence of cheaters, we observe the emergence of a fully mutated population of cells possessing the complex phenotype. Applications of these ideas to cancer initiation and biofilm formation in bacteria are discussed.

Does evolution proceed faster in larger or smaller populations? The relationship between effective population size (Ne) and the rate of evolution has consequences for our ability to understand and interpret genomic variation, and is central to many aspects of evolution and ecology. Many factors affect the relationship between Ne and the rate of evolution, and recent theoretical and empirical studies have shown some surprising and sometimes counterintuitive results. Some mechanisms tend to make the relationship positive, others negative, and they can act simultaneously. The relationship also depends on whether one is interested in the rate of neutral, adaptive, or deleterious evolution. Here, we synthesize theoretical and empirical approaches to understanding the relationship and highlight areas that remain poorly understood.

Functional and biophysical constraints result in site-dependent patterns of protein sequence variability. It is commonly assumed that the key structural determinant of site-specific rates of evolution is the Relative Solvent Accessibility (RSA). However, a recent study found that amino acid substitution rates correlate better with two Local Packing Density (LPD) measures, the Weighted Contact Number (WCN) and the Contact Number (CN), than with RSA. This work aims at a more thorough assessment. To this end, in addition to substitution rates, we considered four other sequence variability scores, four measures of solvent accessibility (SA), and other CN measures. We compared all properties for each protein of a structurally and functionally diverse representative dataset of monomeric enzymes. We show that the best sequence variability measures take into account phylogenetic tree topology. More importantly, we show that both LPD measures (WCN and CN) correlate better than all of the SA measures, regardless of the sequence variability score used. Moreover, the independent contribution of the best LPD measure is approximately four times larger than that of the best SA measure. This study strongly supports the conclusion that a site’s packing density rather than its solvent accessibility is the main structural determinant of its rate of evolution.

Gene duplication is an important mechanism that leads to genetic novelty. Different, nonexclusive processes are likely involved, and many adaptive and nonadaptive events may contribute to the maintenance of duplicated genes. In some teleosts, a duplicate copy of the mammalian ortholog Hemopexin (HPX) is present, known as the warm temperature acclimation-related protein (WAP65). Both WAP65 and HPX have been associated with iron homeostasis due to the affinity to bind the toxic-free heme circulating in the blood stream. We have assessed the evolutionary dynamics of WAP65 and HPX genes to understand the adaptive role of positive selection at both nucleotide and amino acid level. Our results showed an asymmetrical evolution between the paralogs WAP65-1 and WAP65-2 after duplication with a slight acceleration of the evolutionary rate in WAP65-1, but not in WAP65-2, and few sites contributing to the functional distinction between the paralogs, whereas the majority of the protein remained under negative selection or relaxed negative selection. WAP65-1 is functionally more distinct from the ancestral protein function than WAP65-2. HPX is phylogenetically closer to WAP65-2 but even so functional divergence was detected between both proteins. In addition, HPX showed a fast rate of evolution when compared with both WAP65-1 and WAP65-2 genes. The assessed 3-dimensional (3-D) structure of WAP65-1 and WAP65-2 suggests that the functional differences detected are not causing noticeable structural changes in these proteins. However, such subtle changes between WAP65 paralogs may be important to understand the differential gene retention of both copies in 20 out of 30 teleosts species studied.

BACKGROUND Of the respiratory syncytial virus (RSV) genotypes previously described in South Africa during 1997-2002, only GA2 and GA5 persisted until 2006, with BA having replaced all previous RSV-B genotypes. This poses the question whether RSV-A is more stable than RSV-B and whether positive selection drives evolution of genotypes. METHODS RSV-positive specimens were randomly selected during 2009-2012, subtyped, sequenced, and compared to RSV recovered from specimens obtained during 1997-2001 and 2006-2009. Bayesian phylogenetic analysis was performed on the G-protein. RESULTS Phylogenetic analysis indicated that RSV-A genotype GA2 dissolved to form SAA2 (unique to South Africa), NA1 and NA2 (identified in Japan), and ON1 (identified in Canada and having a 72-bp insertion) and that GA5 drifted from 1999-2012 to form 3 subgenotypes (GA5 I-III). RSV-B genotypes all had the 60-bp insertion typical of BA genotypes but clustered into subgenotypes BA8-10. Positive selection was identified in the G-protein of both subtypes, but RSV-A's rate of evolution was slower than that of RSV-B, with the most recent common ancestors dating from 1945 and 1951, respectively. Seven new positively selected sites were identified in South African strains, 2 for RSV-A and 5 for RSV-B. CONCLUSION Positive selection drove both RSV-A and -B genotypes to evolve, resulting in replacement of all genotypes over the 15-year study period in South Africa.

Stronger selection implies faster evolution---that is, the greater the force, the faster the change. This apparently self-evident proposition, however, is derived under the assumption that genetic variation within a population is primarily supplied by mutation (i.e.\ mutation-driven evolution). Here, we show that this proposition does not actually hold for recombination-driven evolution, i.e.\ evolution in which genetic variation is primarily created by recombination rather than mutation. By numerically investigating population genetics models of recombination, migration and selection, we demonstrate that stronger selection can slow down evolution on a perfectly smooth fitness landscape. Through simple analytical calculation, this apparently counter-intuitive result is shown to stem from two opposing effects of natural selection on the rate of evolution. On the one hand, natural selection tends to increase the rate of evolution by increasing the fixation probability of fitter genotypes. On the other hand, natural selection tends to decrease the rate of evolution by decreasing the chance of recombination between immigrants and resident individuals. As a consequence of these opposing effects, there is a finite selection pressure maximizing the rate of evolution. Hence, stronger selection can imply slower evolution if genetic variation is primarily supplied by recombination., Comment: 12 pages, 2 figures

Over calendar time, HIV-1 evolves considerably faster within individuals than it does at the epidemic level. This is a surprising observation since, from basic population genetic theory, we would expect the genetic substitution rate to be similar across different levels of biological organization. Three different mechanisms could potentially cause the observed mismatch in phylogenetic rates of divergence: temporal changes in selection pressure during the course of infection; frequent reversion of adaptive mutations after transmission; and the storage of the virus in the body followed by the preferential transmission of stored ancestral virus. We evaluate each of these mechanisms to determine whether they are likely to make a major contribution to the mismatch in phylogenetic rates. We conclude that the cycling of the virus through very long-lived memory CD4 + T cells, a process that we call ‘store and retrieve’, is probably the major contributing factor to the rate mismatch. The preferential transmission of ancestral virus needs to be integrated into evolutionary models if we are to accurately predict the evolution of immune escape, drug resistance and virulence in HIV-1 at the population level. Moreover, early infection viruses should be the major target for vaccine design, because these are the viral strains primarily involved in transmission.

Tick-borne encephalitis virus (TBEV) is a member of the familyFlaviviridae. It is transmitted byIxodesspp. ticks in a cycle involving rodents and small mammals. TBEV has three subtypes: European, Siberian and Far Eastern. The virus causes thousands of cases of meningoencephalitis in Europe annually, with an increasing trend. The increase may be attributed to a complex network of elements, including climatic, environmental and socio-economic factors. In an attempt to understand the evolutionary history and dispersal of TBEV, to existing genetic data we add two novel complete ORF sequences of TBEV strains from northern Europe and the completion of the genome of four others. Moreover, we provide a unique measure for the natural rate of evolution of TBEV by studying two isolations from the same forest on an island in Åland archipelago 44 years apart. For all isolates, we analysed the phylogeny, rate of evolution and probable time of radiation of the different TBEV strains. The results show that the two lineages of TBEV in differentIxodesspecies have evolved independently for approximately 3300 years. Notably, rapid radiation of TBEV-Eur occurred approximately 300 years ago, without the large-scale geographical clustering observed previously for the Siberian subtype. The measurements from the natural rate of evolution correlated with the estimates done by phylogenetic programs, demonstrating their robustness.

Despite their relatively arginine-rich composition, protamines exhibit a high degree of structural variation. Indeed, the primary structure of these histone H1-related sperm nuclear basic proteins (SNBPs) is not random and is the depository of important phylogenetic information. This appears to be the result of their fast rate of evolution driven by positive selection. The way by which the protein variability participates in the transitions that lead to the final highly condensed chromatin organization of spermatozoa at the end of spermiogenesis is not clearly understood. In this paper we focus on the transient chromatin/nucleoplasm patterning that occurs in either a lamellar step or an inversion step during early and mid-spermiogenesis. This takes place in a small subset of protamines in internally fertilizing species of vertebrates, invertebrates and plants. It involves "complex" protamines that are processed, replaced, or undergo side chain modification (such as phosphorylation or disulfide bond formation) during the histone-to-protamine transition. Characteristic features of such patterning, as observed in TEM photomicrographs, include: constancy of the dominant pattern repeat distance λ(m) despite dynamic changes in developmental morphology, bicontinuity of chromatin and nucleoplasm, and chromatin orientation either perpendicular or parallel to the nuclear envelope. This supports the hypothesis that liquid - liquid phase separation by the mechanism of spinodal decomposition may be occurring during spermiogenesis in these species. Spinodal decomposition involves long wave fluctuations of the local concentration with a low energy barrier and thus differs from the mechanism of nucleation and growth that is known to occur during spermiogenesis in internally fertilizing mammals.

Some previous studies have suggested that rates of evolution inferred using molecular sequences vary substantially depending on the time frame over which they are measured, whereas a number of other studies have argued against this proposition. We examined this issue by separating positions of primate mitochondrial genomes that are under different levels of selection constraints. Our results revealed an order of magnitude variation in the evolutionary rates at constrained sites (including nonsynonymous sites, D-loop, and RNA) and virtually an identical rate of evolution at synonymous sites, independent of the timescales over which they were estimated. Although the evolutionary rate at nonsynonymous sites obtained using the European (H1 haplogroup) mitogenomes is 9-15 times higher than that estimated using the human-chimpanzee pair, in contrast, the rates at synonymous sites are similar between these comparisons. We also show that the ratio of divergence at nonsynonymous to synonymous sites estimated using intra- and interspecific comparisons vary up to nine times, which corroborates our results independent of calibration times.