John J. Welch

The coupling hypothesis: why genome scans may fail to map local adaptation genes

Genomic scans of multiple populations often reveal marker loci with greatly increased differentiation between populations. Often this differentiation coincides in space with contrasts in ecological factors, forming a genetic–environment association (GEA). GEAs imply a role for local adaptation, and so it is tempting to conclude that the strongly differentiated markers are themselves under ecologically based divergent selection, or are closely linked to loci under such selection. Here, we highlight an alternative and neglected explanation: intrinsic (i.e. environment‐independent) pre‐ or post‐zygotic genetic incompatibilities rather than local adaptation can be responsible for increased differentiation. Intrinsic genetic incompatibilities create endogenous barriers to gene flow, also known as tension zones, whose location can shift over time. However, tension zones have a tendency to become trapped by, and therefore to coincide with, exogenous barriers due to ecological selection. This coupling of endogenous and exogenous barriers can occur easily in spatially subdivided populations, even if the loci involved are unlinked. The result is that local adaptation explains where genetic breaks are positioned, but not necessarily their existence, which can be best explained by endogenous incompatibilities. More precisely, we show that (i) the coupling of endogenous and exogenous barriers can easily occur even when ecological selection is weak; (ii) when environmental heterogeneity is fine‐grained, GEAs can emerge at incompatibility loci, but only locally, in places where habitats and gene pools are sufficiently intermingled to maintain linkage disequilibria between genetic incompatibilities, local‐adaptation genes and neutral loci. Furthermore, the association between the locally adapted and intrinsically incompatible alleles (i.e. the sign of linkage disequilibrium between endogenous and exogenous loci) is arbitrary and can form in either direction. Reviewing results from the literature, we find that many predictions of our model are supported, including endogenous genetic barriers that coincide with environmental boundaries, local GEA in mosaic hybrid zones, and inverted or modified GEAs at distant locations. We argue that endogenous genetic barriers are often more likely than local adaptation to explain the majority of Fst‐outlying loci observed in genome scan approaches – even when these are correlated to environmental variables.

Phylogeography takes a relaxed random walk in continuous space and time

Research aimed at understanding the geographic context of evolutionary histories is burgeoning across biological disciplines. Recent endeavors attempt to interpret contemporaneous genetic variation in the light of increasingly detailed geographical and environmental observations. Such interest has promoted the development of phylogeographic inference techniques that explicitly aim to integrate such heterogeneous data. One promising development involves reconstructing phylogeographic history on a continuous landscape. Here, we present a Bayesian statistical approach to infer continuous phylogeographic diffusion using random walk models while simultaneously reconstructing the evolutionary history in time from molecular sequence data. Moreover, by accommodating branch-specific variation in dispersal rates, we relax the most restrictive assumption of the standard Brownian diffusion process and demonstrate increased statistical efficiency in spatial reconstructions of overdispersed random walks by analyzing both simulated and real viral genetic data. We further illustrate how drawing inference about summary statistics from a fully specified stochastic process over both sequence evolution and spatial movement reveals important characteristics of a rabies epidemic. Together with recent advances in discrete phylogeographic inference, the continuous model developments furnish a flexible statistical framework for biogeographical reconstructions that is easily expanded upon to accommodate various landscape genetic features.

Quantifying Adaptive Evolution in the Drosophila Immune System

It is estimated that a large proportion of amino acid substitutions in Drosophila have been fixed by natural selection, and as organisms are faced with an ever-changing array of pathogens and parasites to which they must adapt, we have investigated the role of parasite-mediated selection as a likely cause. To quantify the effect, and to identify which genes and pathways are most likely to be involved in the host–parasite arms race, we have re-sequenced population samples of 136 immunity and 287 position-matched non-immunity genes in two species of Drosophila. Using these data, and a new extension of the McDonald-Kreitman approach, we estimate that natural selection fixes advantageous amino acid changes in immunity genes at nearly double the rate of other genes. We find the rate of adaptive evolution in immunity genes is also more variable than other genes, with a small subset of immune genes evolving under intense selection. These genes, which are likely to represent hotspots of host–parasite coevolution, tend to share similar functions or belong to the same pathways, such as the antiviral RNAi pathway and the IMD signalling pathway. These patterns appear to be general features of immune system evolution in both species, as rates of adaptive evolution are correlated between the D. melanogaster and D. simulans lineages. In summary, our data provide quantitative estimates of the elevated rate of adaptive evolution in immune system genes relative to the rest of the genome, and they suggest that adaptation to parasites is an important force driving molecular evolution.

MODULARITY AND THE COST OF COMPLEXITY

Abstract. In this work we consider the geometrical model of R. A. Fisher, in which individuals are characterized by a number of phenotypic characters under optimizing selection. Recent work on this model by H. A. Orr has demonstrated that as the number of characters increases, there is a significant reduction in the rate of adaptation. Orr has dubbed this a “cost of complexity.” Although there is little evidence as to whether such a cost applies in the natural world, we suggest that the prediction is surprising, at least naively. With this in mind, we examine the robustness of Orrs prediction by modifiying the model in various ways that might reduce or remove the cost. In particular, we explore the suggestion that modular pleiotropy, in which mutations affect only a subset of the traits, could play an important role. We conclude that although modifications of the model can mitigate the cost to a limited extent, Orrs finding is robust.

Estimating the genomewide rate of adaptive protein evolution in Drosophila.

When polymorphism and divergence data are available for multiple loci, extended forms of the McDonald–Kreitman test can be used to estimate the average proportion of the amino acid divergence due to adaptive evolution—a statistic denoted \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\bar{{\alpha}}}}\) \end{document}. But such tests are subject to many biases. Most serious is the possibility that high estimates of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\bar{{\alpha}}}}\) \end{document} reflect demographic changes rather than adaptive substitution. Testing for between-locus variation in α is one possible way of distinguishing between demography and selection. However, such tests have yielded contradictory results, and their efficacy is unclear. Estimates of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\bar{{\alpha}}}}\) \end{document} from the same model organisms have also varied widely. This study clarifies the reasons for these discrepancies, identifying several method-specific biases in widely used estimators and assessing the power of the methods. As part of this process, a new maximum-likelihood estimator is introduced. This estimator is applied to a newly compiled data set of 115 genes from Drosophila simulans, each with each orthologs from D. melanogaster and D. yakuba. In this way, it is estimated that \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\bar{{\alpha}}}}{\approx}0.4{\pm}0.1\) \end{document}, a value that does not vary substantially between different loci or over different periods of divergence. The implications of these results are discussed.

Watching the clock: Studying variation in rates of molecular evolution between species

Evidence is accumulating that rates of molecular evolution vary substantially between species, and that this rate variation is partly determined by species characteristics. A better understanding of how and why rates of molecular evolution vary provides a window on evolutionary processes, and might facilitate improvements in DNA sequence analysis. Measuring rates of molecular evolution and identifying the correlates of rate variation present a unique set of challenges. We describe and compare recent methodological advances that have been proposed to deal with these challenges. We provide a guide to the theoretical basis and practical application of the methods, outline the types of data on which they can be used, and indicate the types of questions they can be used to ask.

A generation time effect on the rate of molecular evolution in invertebrates

The rate of genome evolution varies significantly between species. Evidence is growing that at least some of this variation is associated with species characteristics, such as body size, diversification rate, or population size. One of the strongest correlates of the rate of molecular evolution in vertebrates is generation time (GT): Species with faster generation turnover tend to have higher rates of molecular evolution, presumably because their genomes are copied more frequently and therefore collect more DNA replication errors per unit time. But the GT effect has never been tested for nonvertebrate animals. Here, we present the first general test of the GT effect in invertebrates, using 15 genes from 143 species spread across the major eumetazoan superphyla (including arthropods, nematodes, molluscs, annelids, platyhelminthes, cnidarians, echinoderms, and urochordates). We find significant evidence that rates of molecular evolution are correlated with GT in invertebrates and that this effect applies consistently across genes and taxonomic groups. Furthermore, the GT effect is evident in nonsynonymous substitutions, whereas theory predicts (and most previous evidence has supported) a relationship only in synonymous changes. We discuss both the practical and theoretical implications of these findings.

The incidence of bacterial endosymbionts in terrestrial arthropods

Intracellular endosymbiotic bacteria are found in many terrestrial arthropods and have a profound influence on host biology. A basic question about these symbionts is why they infect the hosts that they do, but estimating symbiont incidence (the proportion of potential host species that are actually infected) is complicated by dynamic or low prevalence infections. We develop a maximum-likelihood approach to estimating incidence, and testing hypotheses about its variation. We apply our method to a database of screens for bacterial symbionts, containing more than 3600 distinct arthropod species and more than 150 000 individual arthropods. After accounting for sampling bias, we estimate that 52% (CIs: 48–57) of arthropod species are infected with Wolbachia, 24% (CIs: 20–42) with Rickettsia and 13% (CIs: 13–55) with Cardinium. We then show that these differences stem from the significantly reduced incidence of Rickettsia and Cardinium in most hexapod orders, which might be explained by evolutionary differences in the arthropod immune response. Finally, we test the prediction that symbiont incidence should be higher in speciose host clades. But while some groups do show a trend for more infection in species-rich families, the correlations are generally weak and inconsistent. These results argue against a major role for parasitic symbionts in driving arthropod diversification.

A Shared Population of Epidemic Methicillin-Resistant Staphylococcus aureus 15 Circulates in Humans and Companion Animals

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a global human health problem causing infections in both hospitals and the community. Companion animals, such as cats, dogs, and horses, are also frequently colonized by MRSA and can become infected. We sequenced the genomes of 46 multilocus sequence type (ST) 22 MRSA isolates from cats and dogs in the United Kingdom and compared these to an extensive population framework of human isolates from the same lineage. Phylogenomic analyses showed that all companion animal isolates were interspersed throughout the epidemic MRSA-15 (EMRSA-15) pandemic clade and clustered with human isolates from the United Kingdom, with human isolates basal to those from companion animals, suggesting a human source for isolates infecting companion animals. A number of isolates from the same veterinary hospital clustered together, suggesting that as in human hospitals, EMRSA-15 isolates are readily transmitted in the veterinary hospital setting. Genome-wide association analysis did not identify any host-specific single nucleotide polymorphisms (SNPs) or virulence factors. However, isolates from companion animals were significantly less likely to harbor a plasmid encoding erythromycin resistance. When this plasmid was present in animal-associated isolates, it was more likely to contain mutations mediating resistance to clindamycin. This finding is consistent with the low levels of erythromycin and high levels of clindamycin used in veterinary medicine in the United Kingdom. This study furthers the “one health” view of infectious diseases that the pathogen pool of human and animal populations are intrinsically linked and provides evidence that antibiotic usage in animal medicine is shaping the population of a major human pathogen. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is major problem in human medicine. Companion animals, such as cats, dogs, and horses, can also become colonized and infected by MRSA. Here, we demonstrate that a shared population of an important and globally disseminated lineage of MRSA can infect both humans and companion animals without undergoing host adaptation. This suggests that companion animals might act as a reservoir for human infections. We also show that the isolates from companion animals have differences in the presence of certain antibiotic resistance genes. This study furthers the “one health” view of infectious diseases by demonstrating that the pool of MRSA isolates in the human and animal populations are shared and highlights how different antibiotic usage patterns between human and veterinary medicine can shape the population of bacterial pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) is major problem in human medicine. Companion animals, such as cats, dogs, and horses, can also become colonized and infected by MRSA. Here, we demonstrate that a shared population of an important and globally disseminated lineage of MRSA can infect both humans and companion animals without undergoing host adaptation. This suggests that companion animals might act as a reservoir for human infections. We also show that the isolates from companion animals have differences in the presence of certain antibiotic resistance genes. This study furthers the “one health” view of infectious diseases by demonstrating that the pool of MRSA isolates in the human and animal populations are shared and highlights how different antibiotic usage patterns between human and veterinary medicine can shape the population of bacterial pathogens.

Reduced Effectiveness of Selection Caused by a Lack of Recombination

Genetic recombination associated with sexual reproduction is expected to have important consequences for the effectiveness of natural selection. These effects may be evident within genomes, in the form of contrasting patterns of molecular variation and evolution in regions with different levels of recombination. Previous work reveals patterns that are consistent with a benefit of recombination for adaptation at the level of protein sequence: both positive selection for adaptive variants and purifying selection against deleterious ones appear to be compromised in regions of low recombination [1-11]. Here, we re-examine these patterns by using polymorphism and divergence data from the Drosophila dot chromosome, which has a long history of reduced recombination. To avoid confounding selection and demographic effects, we collected these data from a species with an apparently stable demographic history, Drosophila americana. We find that D. americana dot loci show several signatures of ineffective purifying and positive selection, including an increase in the rate of protein evolution, an increase in protein polymorphism, and a reduction in the proportion of amino acid substitutions attributable to positive selection.