The effect on homozygosity of selective differences between sites of transposable elements

The behavior of the frequency spectrum of sites of transposable elements for the model proposed by Langley, Brookfield, and Kaplan ((1983) Genetics 104) is studied when some of the sites have weak additive selection against the host. In particular, it is shown that under certain conditions, the expected homozygosity at equilibrium will always be larger when there is variation in selection between sites than when such variation is absent.     

The effect of pollen competition on maintenance of variation in fertilisation ability

Pollen competition in the pistil does not only give flowering plants the possibility to reduce inbreeding but also provides an opportunity for selection of pollen traits that increase male reproductive success. An objection to the existence of selection on pollen competitive ability is that individual variation should quickly vanish if selection is strong. A balance between selection for local adaptation of sporophytes within sites and pollen flow between sites could maintain variation in pollen competitive ability. A prerequisite is that variation in male competitive ability is condition dependent, i.e., influenced by sporophytic adaptation to a patch. This further means that selection on pollen competitive ability can occur both directly on the gamethophytic level and indirectly on the sporophytic level. Our dynamic model shows that maintenance of variation in male competitive ability is more probable when differences in pollen competitive ability influence male fitness, i.e., in cases with pollen competition, than when differences in this trait only is a side effect of selection for more viable individuals. Since there is a connection between the gamethophytic and sporophytic life-phases, the incidence of pollen competition between donors should make it more probable that variability also in sporophyte fitness is preserved.     

The effects of deleterious mutations on evolution at linked sites

The process of evolution at a given site in the genome can be influenced by the action of selection at other sites, especially when these are closely linked to it. Such selection reduces the effective population size experienced by the site in question (the Hill-Robertson effect), reducing the level of variability and the efficacy of selection. In particular, deleterious variants are continually being produced by mutation and then eliminated by selection at sites throughout the genome. The resulting reduction in variability at linked neutral or nearly neutral sites can be predicted from the theory of background selection, which assumes that deleterious mutations have such large effects that their behavior in the population is effectively deterministic. More weakly selected mutations can accumulate by Muller's ratchet after a shutdown of recombination, as in an evolving Y chromosome. Many functionally significant sites are probably so weakly selected that Hill-Robertson interference undermines the effective strength of selection upon them, when recombination is rare or absent. This leads to large departures from deterministic equilibrium and smaller effects on linked neutral sites than under background selection or Muller's ratchet. Evidence is discussed that is consistent with the action of these processes in shaping genome-wide patterns of variation and evolution.     

The effect of hitch-hiking on genes linked to a balanced polymorphism in a subdivided population

The effect of multi-allelic balancing selection on nucleotide diversity at linked neutral sites was investigated by simulations of subdivided populations. The motivation is to understand the behaviour of self-recognition systems such as the MHC and plant self-incompatibility. For neutral sites, two types of subdivision are present: (1) into demes (connected by migration), and (2) into classes defined by different functional alleles at the selected locus (connected by recombination). Previous theoretical studies of each type of subdivision separately have shown that each increases diversity, and decreases the relative frequencies of low-frequency variants, at neutral sites or loci. We show here that the two types of subdivision act non-additively when sampling is at the whole population level, and that subdivision produces some non-intuitive results. For instance, in highly subdivided populations, genetic diversity at neutral sites may decrease with tighter linkage to a selected locus or site. Another conclusion is that, if there is population subdivision, balancing selection leads to decreased expected FST values for neutral sites linked to the selected locus. Finally, we show that the ability to detect balancing selection by its effects on linked variation, using tests such as Tajima's D, is reduced when genes in a subdivided population are sampled from the total population, rather than within demes.     

Using adaptive traits to consider potential consequences of temporal variation in selection: male guppy colour through time and space

Temporal variation in selection is typically evaluated by estimating and comparing selection coefficients in natural populations. Meta‐analyses of these coefficients have yielded important insights, but selection coefficients are limited in several respects, including low statistical power, imperfect fitness surrogates, and uncertainty regarding consequences for trait change. A complementary approach without these limitations is to examine temporal variation in adaptive traits themselves, which is mechanistically easier and more directly relevant to evolutionary consequences. We illustrate this approach by analyzing the colour patterns of male guppies, Poecilia reticulata, from each of six sites in Trinidad in each of 6 years. This system is particularly appropriate for our study because key aspects of colour variation are genetically‐based and responsive to selection. However, although spatial patterns of colour variation have been extensively considered in this system, no study has yet formally assessed annual temporal variation in non‐manipulated populations. Matching previous conclusions for the guppy system, we find that guppies from different sites manifest different colour patterns in association with different predation regimes. We here add the new finding that, although some temporal variation is present, spatial patterns of colour variation are generally consistent across years. These results suggest that, when considering adaptive traits, spatial variation is more important than temporal variation, although our study system might be exceptional in this regard. Additional studies examining spatiotemporal variation in adaptive traits could help to improve our understanding of the role that spatiotemporal variation in selection plays in the evolutionary process. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 112 , 108–122.     

WHY WE ARE NOT DEAD ONE HUNDRED TIMES OVER

The possibility of pervasive weak selection at tens or hundreds of millions of sites across the genome, suggested by recent studies of silent site DNA sequence variation and divergence, raises the problem of the survival of the population in the face of the large genetic load that may result. Two alternative resolutions of this problem are presented for populations where recombination is sufficiently frequent that different sites under selection evolve independently. One invokes weak stabilizing selection, of the magnitude compatible with abundant silent site variability. This can be shown to produce only a modest genetic load, due to the effectiveness of even weak stabilizing selection in keeping the trait mean close to the optimum. The other invokes soft selection, whereby individuals compete for a limiting resource whose abundance determines the absolute fitness of the population. Weak purifying selection at a large number of sites produces only a small variance in fitness among individuals within the population, due to the fact that most sites are fixed rather than polymorphic. Even when it produces a large genetic load, it is compatible with the observations on fitness variance when selection is soft. It may be very difficult to distinguish between these two possibilities.     

Within- and between-species DNA sequence variation and the 'footprint' of natural selection

Extensive DNA data emerging from genome-sequencing projects have revitalized interest in the mechanisms of molecular evolution. Although the contribution of natural selection at the molecular level has been debated for over 30 years, the relevant data and appropriate statistical methods to address this issue have only begun to emerge. This paper will first present the predominant models of neutral, nearly neutral, and adaptive molecular evolution. Then, a method to identify the role of natural selection in molecular evolution by comparing within- and between-species DNA sequence variation will be presented. Computer simulations show that such methods are powerful for detecting even very weak selection. Examination of DNA variation data within and between Drosophila species suggests that 'silent' sites evolve under a balance between weak selection and genetic drift. Simulated data also show that sequence comparisons are a powerful method to detect adaptive protein evolution, even when selection is weak or affects a small fraction of nucleotide sites. In the Drosophila data examined, positive selection appears to be a predominant force in protein evolution.     

On the effects of background selection in small populations on comparisons of molecular variation

Deleterious mutations affect genetic variation at linked neutral loci. Neutral variation can be reduced due to background selection, but in small population and with tight linkage such variation may increase due to associative overdominance. Here I report the results of computer simulations of diploid genotypes in small populations, where I look at the effect of deleterious mutations and linkage on comparisons of intra- and interspecific variation. Each chromosome consisted of 2000 loci where deleterious and neutral mutations occurred. The ratio of nonsynonymous to synonymous substitution rates (Ka/Ks) either increases with tight linkage or is unaffected, depending on the strength of selection. The ratio of the numbers of segregating mutations to the number of fixed mutations decreases under the conditions leading to background selection but can increase at tight linkage. Numbers of segregating sites (Sn) are less affected than nucleotide site diversity (pi), pi reduces more than Sn at intermediate linkage, but pi increases more than Sn when linkage is tight. Similar effects as found for Sn and pi are observed for heterozygosity and variance in allele size of tandem repeat loci.     

SPATIOTEMPORAL VARIATION IN LINEAR NATURAL SELECTION ON BODY COLOR IN WILD GUPPIES (POECILIA RETICULATA)

We conducted 10 mark–recapture experiments in natural populations of Trinidadian guppies to test hypotheses concerning the role of viability selection in geographic patterns of male color variation. Previous work has reported that male guppies are more colorful in low‐predation sites than in high‐predation sites. This pattern of phenotypic variation has been theorized to reflect differences in the balance between natural (viability) selection that disfavors bright male color (owing to predation) and sexual selection that favors bright color (owing to female choice). Our results support the prediction that male color is disfavored by viability selection in both predation regimes. However, it does not support the prediction that viability selection against male color is weaker in low‐predation experiments. Instead, some of the most intense bouts of selection against color occurred in low‐predation experiments. Our results illustrate considerable spatiotemporal variation in selection among experiments, but such variation was not generally correlated with local patterns of color diversity. More complex selective interactions, possibly including the indirect effects of predators on variation in mating behavior, as well as other environmental factors, might be required to more fully explain patterns of secondary sexual trait variation in this system.     

Evolutionary Constraint and Disease Associations of Post-Translational Modification Sites in Human Genomes

Interpreting the impact of human genome variation on phenotype is challenging. The functional effect of protein-coding variants is often predicted using sequence conservation and population frequency data, however other factors are likely relevant. We hypothesized that variants in protein post-translational modification (PTM) sites contribute to phenotype variation and disease. We analyzed fraction of rare variants and non-synonymous to synonymous variant ratio (Ka/Ks) in 7,500 human genomes and found a significant negative selection signal in PTM regions independent of six factors, including conservation, codon usage, and GC-content, that is widely distributed across tissue-specific genes and function classes. PTM regions are also enriched in known disease mutations, suggesting that PTM variation is more likely deleterious. PTM constraint also affects flanking sequence around modified residues and increases around clustered sites, indicating presence of functionally important short linear motifs. Using target site motifs of 124 kinases, we predict that at least ∼180,000 motif-breaker amino acid residues that disrupt PTM sites when substituted, and highlight kinase motifs that show specific negative selection and enrichment of disease mutations. We provide this dataset with corresponding hypothesized mechanisms as a community resource. As an example of our integrative approach, we propose that PTPN11 variants in Noonan syndrome aberrantly activate the protein by disrupting an uncharacterized cluster of phosphorylation sites. Further, as PTMs are molecular switches that are modulated by drugs, we study mutated binding sites of PTM enzymes in disease genes and define a drug-disease network containing 413 novel predicted disease-gene links.     

The Effects of Mutation and Natural Selection on Codon Bias in the Genes of Drosophila

Codon bias varies widely among the loci of Drosophila melanogaster, and some of this diversity has been explained by variation in the strength of natural selection. A study of correlations between intron and coding region base composition shows that variation in mutation pattern also contributes to codon bias variation. This finding is corroborated by an analysis of variance (ANOVA), which shows a tendency for introns from the same gene to be similar in base composition. The strength of base composition correlations between introns and codon third positions is greater for genes with low codon bias than for genes with high codon bias. This pattern can be explained by an overwhelming effect of natural selection, relative to mutation, in highly biased loci. In particular, this correlation is absent when examining fourfold degenerate sites of highly biased genes. In general, it appears that selection acts more strongly in choosing among fourfold degenerate codons than among twofold degenerate codons. Although the results indicate regional variation in mutational bias, no evidence is found for large scale regions of compositional homogeneity.     

Identifying loci under selection across contrasting environments in Avena barbata using quantitative trait locus mapping

We constructed recombinant inbred lines of a cross between naturally occurring ecotypes of Avena barbata (Pott ex Link), Poaceae, associated with contrasting moisture environments. These lines were assessed for fitness in common garden reciprocal transplant experiments in two contrasting field sites in each of two years, as well as a novel, benign greenhouse environment. An AFLP (amplified fragment length polymorphism) linkage map of 129 markers spanned 644 cM in 19 linkage groups, which is smaller, with more linkage groups, than expected. Therefore parts of the A. barbata genome remain unmapped, possibly because they lack variation between the ecotypes. Nevertheless, we identified QTL (quantitative trait loci) under selection in both native environments and in the greenhouse. Across years at the same site, the same loci remain under selection, for the same alleles. Across sites, an overlapping set of loci are under selection with either (i) the same alleles favoured at both sites or (ii) loci under selection at one site and neutral at the other. QTL under selection in the greenhouse were generally unlinked to those under selection in the field because selection acted on a different trait. We found little evidence that selection favours alternate alleles in alternate environments, which would be necessary if genotype by environment interaction were to maintain genetic variation in A. barbata. Additive effect QTL were best able to explain the genetic variation among recombinant inbred lines for the greenhouse environment where heritability was highest, and past selection had not eliminated variation.     

SPATIAL AND TEMPORAL VARIATION IN SELECTION ON CORRELATED LIFE-HISTORY TRAITS AND PLANT SIZE IN CHAMAECRISTA FASCICULATA

Intraspecific studies of selection on multiple traits of a plant's life history provide insight as to how the composite life history of an organism evolves. Current understanding of selection on plant life-history traits is deficient in three important areas: 1) the effects of selection through correlated traits, 2) the effects of selection on a trait throughout the plant's lifetime, and 3) spatial and temporal variation in selection on plant life-history traits among populations and years. This study documents spatial and temporal variation in selection on three life-history and two morphological traits for two natural populations of Chamaecrista fasciculata, a native summer annual. Life-history and morphological traits (date of seedling emergence, size at establishment, size prior to reproduction, date of initial flowering, and date of initial fruit maturation) varied significantly between sites and/or years. Selection on traits varied either spatially, between sites and among transects within one site, or temporally, between years. In addition, life-history traits were phenotypically correlated among themselves and with morphological traits; correlations were generally constant over time and space. Indirect selection caused changes in means and variances in traits not under direct selection, but which were correlated with traits under selection. Selection on date of emergence varied in direction and magnitude among different life-cycle stages, while selection on other traits varied only in magnitude among life stages of the plant. This study documents the complexity of the selective process and the importance of considering multiple life stages and traits when studying the evolution of life-history traits.     

The opportunity to be misled in studies of sexual selection

It is a challenge to measure sexual selection because both stochastic events (chance) and deterministic factors (selection) generate variation in individuals' reproductive success. Most researchers realize that random events ('noise') make it difficult to detect a relationship between a trait and mating success (i.e. the presence of sexual selection). There is, however, less appreciation of the dangers that arise if stochastic events vary systematically. Systematic variation makes variance-based approaches to measuring the role of selection problematic. This is why measuring the opportunity for sexual selection (I(s) and I(mates)) is so vulnerable to misinterpretation. Although I(s) does not measure actual sexual selection (because it includes stochastic variation in mating/fertilization success) it is often implicitly assumed that it will be correlated with the actual strength of sexual selection. The hidden assumption is that random noise is randomly distributed across populations, species or the sexes. Here we present a simple numerical example showing why this practice is worrisome. Specifically, we show that chance variation in mating success is higher when there are fewer potential mates per individual of the focal sex [i.e. when the operational sex ratio (OSR), is more biased]. This will lead to the OSR covarying with I(s) even when the strength of sexual selection is unaffected by the OSR. This can generate false confidence in identifying factors that determine variation in the strength of sexual selection. We emphasize that in nature, even when sexual selection is strong, chance variation in mating success is still inevitable because the number of mates per individual is a discrete number. We hope that our worked example will clarify a recent debate about how best to measure sexual selection.     

Patterns of mutation and selection at synonymous sites in Drosophila

That natural selection affects molecular evolution at synonymous sites in protein-coding sequences is well established and is thought to predominantly reflect selection for translational efficiency/accuracy mediated through codon bias. However, a recently developed maximum likelihood framework, when applied to 18 coding sequences in 3 species of Drosophila, confirmed an earlier report that the Notch gene in Drosophila melanogaster was evolving under selection in favor of those codons defined as unpreferred in this species. This finding opened the possibility that synonymous sites may be subject to a variety of selective pressures beyond weak selection for increased frequencies of the codons currently defined as "preferred" in D. melanogaster. To further explore patterns of synonymous site evolution in Drosophila in a lineage-specific manner, we expanded the application of the maximum likelihood framework to 8,452 protein coding sequences with well-defined orthology in D. melanogaster, Drosophila sechellia, and Drosophila yakuba. Our analyses reveal intragenomic and interspecific variation in mutational patterns as well as in patterns and intensity of selection on synonymous sites. In D. melanogaster, our results provide little statistical evidence for recent selection on synonymous sites, and Notch remains an outlier. In contrast, in D. sechellia our findings provide evidence in support of selection predominantly in favor of preferred codons. However, there is a small subset of genes in this species that appear to be evolving under selection in favor of unpreferred codons, which indicates that selection on synonymous sites is not limited to the preferential fixation of mutations that enhance the speed or accuracy of translation in this species.     

Geographic variation of wing morphology of great fruit‐eating bats (Artibeus lituratus): environmental,genetic and spatial correlates of phenotypic differences

Responses of species to environmental gradients are important and frequent determinants of geographic phenotypic variation that can drive adaptive processes. Nonetheless, random genetic processes such as drift can also result in geographic variation in phenotypes, and should be evaluated before implicating selection as the process driving phenotypic change. We examined geographic variation in wing morphology of Artibeus lituratus among 18 different sites distributed across interior Atlantic Forest of Paraguay and Argentina. Moreover, we contrasted geographic variation with environmental, spatial, and genetic variation to test hypotheses related to selection and drift and their impacts on wing morphology. For A. lituratus distributed across interior Atlantic Forest, significant differences among sites characterized variation in wing morphology. Geographic variation was significantly related to climatic variables but not spatial or genetic distances. Such a pattern suggests that phenotypic variation is related to selection for particular environmental regimes, and not genetic drift. Four significant dimensions of phenotypic variation were determined. Three dimensions were related to variation among individuals in terms of wing tips, whereas one was related to overall body size. Wing tips are important for manoeuverability during flight and differences among sites likely reflect differences in forest and vegetation structure that must be managed during foraging. Although climate provides good surrogates for environmental variation, it is probably only an indirect cue of selection regimes that determine variation in wing morphology. Future studies should evaluate more direct environmental measures such as vegetation structure when attempting to interpret geographical variation in wing morphology.     

An investigation of the cause of low variability on the fourth chromosome of Drosophila melanogaster.

The fourth chromosome of Drosophila melanogaster lacks meiotic recombination. There is also a lack of nucleotide variation on the chromosome. This lack of variation could have been caused by a recent selective sweep, by background selection, or by a combination of these two forces. It should be possible to differentiate between the two mechanisms by studying the frequencies of polymorphic sites on the chromosome: a selective sweep should have resulted in low-frequency polymorphisms, whereas higher frequency polymorphisms would indicate the action of background selection. We have analyzed retrotransposable element insertions on the fourth chromosome in 11 strains of D. melanogaster. The polymorphisms found have a range of frequencies, with the presence of some insertions with high frequencies suggesting that the lack of variation is the result of background selection. We summarize the data using two statistics: the number of sites shared by more than one of the sample of 11 chromosomes (internal sites) and the mean number of transposable element differences in presence or absence between the sampled chromosomes. Simulations indicate that a selective sweep occurring more than 15,000 (0.03N) generations ago cannot be ruled out from the number of internal sites, although the number of differences between the chromosomes suggests either background selection or a sweep occurring more than 60,000 (0.12N) generations ago. Our results show no homoplasies and are thus consistent with no recombination occurring on the chromosome. The difficulties of distinguishing between the models using polymorphism data are discussed.     

Anti-apostatic selection by wild birds on quasi-natural morphs of the land snail Cepaea hortensis: a generalised linear mixed models approach

Anti-apostatic selection occurs when predators feed disproportionately on rare prey, a process that leads to a decrease in variation within prey populations. Most of the evidence for this phenomenon comes from experiments using artificial prey items distinguished by simple artificial colour differences. We describe an experiment performed at 10 different sites in which we tested whether selection by wild birds is anti-apostatic when presented with high density populations of shells of the polymorphic land snail, Cepaea hortensis , stuffed with pastry. At each site we presented two sorts of populations in sequence: 45 yellow unbanded with 5 yellow banded, and 5 yellow unbanded with 45 yellow banded. Selection was measured using an analysis based on generalised linear mixed models (GLMMs) that has broad applicability to all resource selection studies where extraneous variance is a problem. Using this analytic method, we found that birds altered their behaviour to produce significant anti-apostatic selection in direct response to changes in frequency of the quasi-natural Cepaea morphs.