Fluctuating selection models and Mcdonald-Kreitman type analyses

It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate the consequences of fluctuating selection pressures on the quantification of adaptive evolution using McDonald-Kreitman (MK) style approaches. In agreement with previous work, we show that fluctuating selection can generate evidence of adaptive evolution even when the expected strength of selection on a mutation is zero. However, we also find that the mutations, which contribute to both polymorphism and divergence tend, on average, to be positively selected during their lifetime, under fluctuating selection models. This is because mutations that fluctuate, by chance, to positive selected values, tend to reach higher frequencies in the population than those that fluctuate towards negative values. Hence the evidence of positive adaptive evolution detected under a fluctuating selection model by MK type approaches is genuine since fixed mutations tend to be advantageous on average during their lifetime. Never-the-less we show that methods tend to underestimate the rate of adaptive evolution when selection fluctuates

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

Fixation of genetic variation and optimization of gene expression: The speed of evolution in isolated lizard populations undergoing Reverse Island Syndrome

The ecological theory of island biogeography suggests that mainland populations should be more genetically divergent from those on large and distant islands rather than from those on small and close islets. Some island populations do not evolve in a linear way, but the process of divergence occurs more rapidly because they undergo a series of phenotypic changes, jointly known as the Island Syndrome. A special case is Reversed Island Syndrome (RIS), in which populations show drastic phenotypic changes both in body shape, skin colouration, age of sexual maturity, aggressiveness, and food intake rates. The populations showing the RIS were observed on islets nearby mainland and recently raised, and for this they are useful models to study the occurrence of rapid evolutionary change. We investigated the timing and mode of evolution of lizard populations adapted through selection on small islets. For our analyses, we used an ad hoc model system of three populations: wild-type lizards from the mainland and insular lizards from a big island (Capri, Italy), both Podarcis siculus siculus not affected by the syndrome, and a lizard population from islet (Scopolo) undergoing the RIS (called P. s. coerulea because of their melanism). The split time of the big (Capri) and small (Scopolo) islands was determined using geological events, like sea-level rises. To infer molecular evolution, we compared five complete mitochondrial genomes for each population to reconstruct the phylogeography and estimate the divergence time between island and mainland lizards. We found a lower mitochondrial mutation rate in Scopolo lizards despite the phenotypic changes achieved in approximately 8,000 years. Furthermore, transcriptome analyses showed significant differential gene expression between islet and mainland lizard populations, suggesting the key role of plasticity in these unpredictable environments

ZRT1 harbors an excess of nonsynonymous polymorphism and shows evidence of balancing selection in Saccharomyces cerevisiae

Estimates of the fraction of nucleotide substitutions driven by positive selection vary widely across different species. Accounting for different estimates of positive selection has been difficult, in part because selection on polymorphism within a species is known to obscure a signal of positive selection between species. While methods have been developed to control for the confounding effects of negative selection against deleterious polymorphism, the impact of balancing selection on estimates of positive selection has not been assessed. In Saccharomyces cerevisiae, there is no signal of positive selection within protein coding sequences as the ratio of nonsynonymous to synonymous polymorphism is higher than that of divergence. To investigate the impact of balancing selection on estimates of positive selection we examined five genes with high rates of nonsynonymous polymorphism in S. cerevisiae relative to divergence from S. paradoxus. One of the genes, a high affinity zinc transporter ZRT1, shows an elevated rate of synonymous polymorphism indicative of balancing selection. The high rate of synonymous polymorphism coincides with nonsynonymous divergence between three haplotype groups, which we find to be functionally indistinguishable. We conclude that balancing selection is not likely to be a common cause of genes harboring a large excess of nonsynonymous polymorphism in yeast

Inferring the Distribution of Selective Effects from a Time Inhomogeneous Model

We have developed a Poisson random field model for estimating the distribution of selective effects of newly arisen nonsynonymous mutations that could be observed as polymorphism or divergence in samples of two related species under the assumption that the two species populations are not at mutation-selection-drift equilibrium. The model is applied to 91Drosophila genes by comparing levels of polymorphism in an African population of D. melanogaster with divergence to a reference strain of D. simulans. Based on the difference of gene expression level between testes and ovaries, the 91 genes were classified as 33 male-biased, 28 female-biased, and 30 sex-unbiased genes. Under a Bayesian framework, Markov chain Monte Carlo simulations are implemented to the model in which the distribution of selective effects is assumed to be Gaussian with a mean that may differ from one gene to the other to sample key parameters. Based on our estimates, the majority of newly-arisen nonsynonymous mutations that could contribute to polymorphism or divergence in Drosophila species are mildly deleterious with a mean scaled selection coefficient of -2.81, while almost 86% of the fixed differences between species are driven by positive selection. There are only 16.6% of the nonsynonymous mutations observed in sex-unbiased genes that are under positive selection in comparison to 30% of male-biased and 46% of female-biased genes that are beneficial. We also estimated that D. melanogaster and D. simulans may have diverged 1.72 million years ago

Molecular Evolution of Four Salivary Proteins within Species of the Anopheles gambiae Complex

Some of the primary vectors of human malaria include female mosquitoes from the Anopheles gambiae complex, which is comprised of at least six different species within the genus Anopheles, including A. gambiae (M/S forms), A. arabiensis, A. melas, A. bwambae, A. merus, and A. quadriannulatus. Salivary gland proteins within the Anopheles gambiae complex interact with a vertebrate host’s immune system by controlling vasodilatation, inflammation, and platelet aggregation at the feeding site on the vertebrate host. The way certain salivary proteins are expressed within different mosquito species has been studied, but there is still a need for a comparison between species of close proximity, such as those in the A. gambiae complex. This comparison could reveal genes that may interact with a host’s immune system or with malaria parasites and hence may be under selection. Such genes may have crucial roles in the adaptation to specific hosts. For example, an excess of non-synonymous fixed differences in the gene would mean directional or positive selection, which may have resulted from interaction with various hosts. To gain further insight into 4 specific salivary gland proteins (Anophelin, Ichit, Glycosidase, and Lysozyme), their patterns of polymorphism were analyzed in 3 species of the An. gambiae complex (Anopheles gambiae M and S forms, Anopheles melas, and Anopheles arabiensis). After analyzing these genes using several statistical tests, the comparison showed that three of the four genes, Anophelin, Ichit, and Glycosidase are highly conserved with no signs of positive selection or fixed differences between A. gambiae, A. arabiensis, and A. melas species. Further research exploring the genetic variation of other salivary proteins within the A. gambiae complex may identify proteins that are undergoing positive selection. This could locate genes involved in vector competence, either preventing or enhancing disease transmission in Anopheles mosquitoes

Evolution Of The Protein-Coding Genes In The Genomes Of The Mycoplasmatales

The bacterial species belonging to the order Mycoplasmatales have highly truncated genomes, and are thus ideal for studying genome evolution patterns. Fourteen members (twelve species) of this order were selected for study of genome evolution based on gene function and phylogeny. A database was constructed that consisting of the set of genes that are common to all of these species, and these genes were further subdivided based on their functions. A Bayesian phylogenetic tree was also constructed from the 16 S ribosomal DNA sequences from these species and robust clades were identified for testing the influence of selection on gene evolution, from which the clades were selected and tested for evidence of natural selection. Two separate statistical techniques, namely the codon substitution models and McDonald-Kreitman tests were used to analyze the presence or absence of selection for genes in different functional categories. The studies demonstrated that the set of genes associated with cellular processes show the highest percentage of selection and are likely to play a crucial role in Mycoplasma evolution (for example, by altering the arrangement of antigens on the cell surface and thus enabling a particular Mycoplasma species to expand its host range). The presence of selection could only be identified at the earliest divisions of the phylogeny. Tests were also performed to detect the presence of a number of neutral genetic processes that can potentially confound detection of patterns of selection. None of these processes were found to affect the results of the analyses. The study has the potential to identify genes, gene complexes or even pathways that may be involved directly or indirectly in speciation