Partial Selective Sweeps Research Articles

Global, asynchronous partial sweeps at multiple insecticide resistance genes in Aedes mosquitoes

Aedes aegypti (yellow fever mosquito) and Ae. albopictus (Asian tiger mosquito) are globally invasive pests that confer the world’s dengue burden. Insecticide-based management has led to the evolution of insecticide resistance in both species, though the genetic architecture and geographical spread of resistance remains incompletely understood. This study investigates partial selective sweeps at resistance genes on two chromosomes and characterises their spread across populations. Sweeps at the voltage-sensitive sodium channel (VSSC) gene on chromosome 3 correspond to one resistance-associated nucleotide substitution in Ae. albopictus and three in Ae. aegypti, including two substitutions at the same nucleotide position (F1534C) that have evolved and spread independently. In Ae. aegypti, we also identify partial sweeps at a second locus on chromosome 2. This locus contains 15 glutathione S-transferase (GST) epsilon class genes with significant copy number variation among populations and where three distinct genetic backgrounds have spread across the Indo-Pacific region, the Americas, and Australia. Local geographical patterns and linkage networks indicate VSSC and GST backgrounds probably spread at different times and interact locally with different genes to produce resistance phenotypes. These findings highlight the rapid global spread of resistance and are evidence for the critical importance of GST genes in resistance evolution.

Temporal challenges in detecting balancing selection from population genomic data.

The role of balancing selection in maintaining genetic variation remains an open question in population genetics. Recent years have seen numerous studies identifying candidate loci potentially experiencing balancing selection, most predominantly in human populations. There are however numerous alternative evolutionary processes that may leave similar patterns of variation, thereby potentially confounding inference, and the expected signatures of balancing selection additionally change in a temporal fashion. Here we use forward-in-time simulations to quantify expected statistical power to detect balancing selection using both site frequency spectrum- and linkage disequilibrium-based methods under a variety of evolutionarily realistic null models. We find that whilst site frequency spectrum-based methods have little power immediately after a balanced mutation begins segregating, power increases with time since the introduction of the balanced allele. Conversely, linkage disequilibrium-based methods have considerable power whilst the allele is young, and power dissipates rapidly as the time since introduction increases. Taken together, this suggests that site frequency spectrum-based methods are most effective at detecting long-term balancing selection (>25N generations since the introduction of the balanced allele) whilst linkage disequilibrium-based methods are effective over much shorter timescales (<1N generations), thereby leaving a large time frame over which current methods have little power to detect the action of balancing selection. Finally, we investigate the extent to which alternative evolutionary processes may mimic these patterns, and demonstrate the need for caution in attempting to distinguish the signatures of balancing selection from those of both neutral processes (e.g. population structure and admixture) as well as of alternative selective processes (e.g. partial selective sweeps).

Extraordinary selection on the human X chromosome associated with archaic admixture.

The X chromosome in non-African humans shows less diversity and less Neanderthal introgression than expected from neutral evolution. Analyzing 162 human male X chromosomes worldwide, we identified fourteen chromosomal regions where nearly identical haplotypes spanning several hundred kilobases are found at high frequencies in non-Africans. Genetic drift alone cannot explain the existence of these haplotypes, which must have been associated with strong positive selection in partial selective sweeps. Moreover, the swept haplotypes are entirely devoid of archaic ancestry as opposed to the non-swept haplotypes in the same genomic regions. The ancient Ust'-Ishim male dated at 45,000 before the present (BP)also carries the swept haplotypes, implying that selection on the haplotypes must have occurred between 45,000 and 55,000 years ago. Finally, we find that the chromosomal positions of sweeps overlap previously reported hotspots of selectivesweeps in great ape evolution, suggesting a mechanism of selection unique to X chromosomes.

Coherent synthesis of genomic associations with phenotypes and home environments.

Local adaptation is often studied via (i) multiple common garden experiments comparing performance of genotypes in different environments and (ii) sequencing genotypes from multiple locations and characterizing geographic patterns in allele frequency. Both approaches aim to characterize the same pattern (local adaptation), yet the complementary information from each has not yet been coherently integrated. Here, we develop a genome-wide association model of genotype interactions with continuous environmental gradients (G×E), that is reaction norms. We present an approach to impute relative fitness, allowing us to coherently synthesize evidence from common garden and genome-environment associations. Our approach identifies loci exhibiting environmental clines where alleles are associated with higher fitness in home environments. Simulations show our approach can increase power to detect loci causing local adaptation. In a case study on Arabidopsis thaliana, most identified SNPs exhibited home allele advantage and fitness trade-offs along climate gradients, suggesting selective gradients can maintain allelic clines. SNPs exhibiting G×E associations with fitness were enriched in genic regions, putative partial selective sweeps and associations with an adaptive phenotype (flowering time plasticity). We discuss extensions for situations where only adaptive phenotypes other than fitness are available. Many types of data may point towards the loci underlying G×E and local adaptation; coherent models of diverse data provide a principled basis for synthesis.

A haplotype method detects diverse scenarios of local adaptation from genomic sequence variation.

Identifying genomic targets of population-specific positive selection is a major goal in several areas of basic and applied biology. However, it is unclear how often such selection should act on new mutations versus standing genetic variation or recurrent mutation, and furthermore, favoured alleles may either become fixed or remain variable in the population. Very few population genetic statistics are sensitive to all of these modes of selection. Here, we introduce and evaluate the Comparative Haplotype Identity statistic (χMD ), which assesses whether pairwise haplotype sharing at a locus in one population is unusually large compared with another population, relative to genomewide trends. Using simulations that emulate human and Drosophila genetic variation, we find that χMD is sensitive to a wide range of selection scenarios, and for some very challenging cases (e.g. partial soft sweeps), it outperforms other two-population statistics. We also find that, as with FST , our haplotype approach has the ability to detect surprisingly ancient selective sweeps. Particularly for the scenarios resembling human variation, we find that χMD outperforms other frequency- and haplotype-based statistics for soft and/or partial selective sweeps. Applying χMD and other between-population statistics to published population genomic data from D.melanogaster, we find both shared and unique genes and functional categories identified by each statistic. The broad utility and computational simplicity of χMD will make it an especially valuable tool in the search for genes targeted by local adaptation.

Inferring the demographic history of Drosophila subobscura from nucleotide variation at regions not affected by chromosomal inversions.

Drosophila subobscura presents a rich and complex chromosomal inversion polymorphism. It can thus be considered a model system (i) to study the mechanisms originating inversions and how inversions affect the levels and patterns of variation in the inverted regions and (ii) to study adaptation at both the single-gene and chromosomal inversion levels. It is therefore important to infer its demographic history as previous information indicated that its nucleotide variation is not at mutation-drift equilibrium. For that purpose, we sequenced 16 noncoding regions distributed across those parts of the J chromosome not affected by inversions in the studied population and possibly either by other selective events. The pattern of variation detected in these 16 regions is similar to that previously reported within different chromosomal arrangements, suggesting that the latter results would, thus, mainly reflect recent demographic events rather than the partial selective sweep imposed by the origin and frequency increase of inversions. Among the simple demographic models considered in our Approximate Bayesian Computation analysis of variation at the 16 regions, the model best supported by the data implies a population size expansion soon after the penultimate glacial period. This model constitutes a better null model, and it is therefore an important resource for subsequent studies aiming among others to uncover selective events across the species genome. Our results also highlight the importance of introducing the possibility of multiple hits in the coalescent simulations with an outgroup.

Soft shoulders ahead: spurious signatures of soft and partial selective sweeps result from linked hard sweeps.

Characterizing the nature of the adaptive process at the genetic level is a central goal for population genetics. In particular, we know little about the sources of adaptive substitution or about the number of adaptive variants currently segregating in nature. Historically, population geneticists have focused attention on the hard-sweep model of adaptation in which a de novo beneficial mutation arises and rapidly fixes in a population. Recently more attention has been given to soft-sweep models, in which alleles that were previously neutral, or nearly so, drift until such a time as the environment shifts and their selection coefficient changes to become beneficial. It remains an active and difficult problem, however, to tease apart the telltale signatures of hard vs. soft sweeps in genomic polymorphism data. Through extensive simulations of hard- and soft-sweep models, here we show that indeed the two might not be separable through the use of simple summary statistics. In particular, it seems that recombination in regions linked to, but distant from, sites of hard sweeps can create patterns of polymorphism that closely mirror what is expected to be found near soft sweeps. We find that a very similar situation arises when using haplotype-based statistics that are aimed at detecting partial or ongoing selective sweeps, such that it is difficult to distinguish the shoulder of a hard sweep from the center of a partial sweep. While knowing the location of the selected site mitigates this problem slightly, we show that stochasticity in signatures of natural selection will frequently cause the signal to reach its zenith far from this site and that this effect is more severe for soft sweeps; thus inferences of the target as well as the mode of positive selection may be inaccurate. In addition, both the time since a sweep ends and biologically realistic levels of allelic gene conversion lead to errors in the classification and identification of selective sweeps. This general problem of "soft shoulders" underscores the difficulty in differentiating soft and partial sweeps from hard-sweep scenarios in molecular population genomics data. The soft-shoulder effect also implies that the more common hard sweeps have been in recent evolutionary history, the more prevalent spurious signatures of soft or partial sweeps may appear in some genome-wide scans.

Geographical delimitation of a partial selective sweep in African Drosophila melanogaster

Positive selection leaves characteristic footprints on DNA variation but detecting such patterns is challenging as the age, the intensity and the mode of selection as well as demography and evolutionary parameters (mutation and recombination rates) all play roles and these are difficult to disentangle. We recorded nucleotide variation in a sample of isogenic chromosomes from a western African population of Drosophila melanogaster at a locus (Fbp2) for which a partial selective sweep had previously been reported. We compared this locus to four other genes from the same chromosomes and from a European and an East African population. Then, we assessed Fbp2 variation in a sample of 370 chromosomes covering a comprehensive geographic sampling of 16 African localities. The signature of selection was tested while accounting for the demographic history of the populations. We found a significant signal of selection in two West African localities including Ivory Coast. Variation at Fpb2 would thus represent a case of an ongoing selective sweep in the range of this species. A weaker, nonsignificant, signal of selection was, however, apparent in some other populations, thus leaving open several possibilities: (i) the selective sweep originated in Ivory Coast and has spread to the rest of the continent; (ii) several African populations report the signature of a selective event having occurred in an ancestral population; (iii) this genome region is subject to independent selective events in African populations; and (iv) A neutral scenario with population subdivision and local bottleneck cannot be fully excluded to explain the molecular patterns observed in some populations.

ANTAGONISTIC VERSUS NONANTAGONISTIC MODELS OF BALANCING SELECTION: CHARACTERIZING THE RELATIVE TIMESCALES AND HITCHHIKING EFFECTS OF PARTIAL SELECTIVE SWEEPS

Antagonistically selected alleles--those with opposing fitness effects between sexes, environments, or fitness components--represent an important component of additive genetic variance in fitness-related traits, with stably balanced polymorphisms often hypothesized to contribute to observed quantitative genetic variation. Balancing selection hypotheses imply that intermediate-frequency alleles disproportionately contribute to genetic variance of life-history traits and fitness. Such alleles may also associate with population genetic footprints of recent selection, including reduced genetic diversity and inflated linkage disequilibrium at linked, neutral sites. Here, we compare the evolutionary dynamics of different balancing selection models, and characterize the evolutionary timescale and hitchhiking effects of partial selective sweeps generated under antagonistic versus nonantagonistic (e.g., overdominant and frequency-dependent selection) processes. We show that the evolutionary timescales of partial sweeps tend to be much longer, and hitchhiking effects are drastically weaker, under scenarios of antagonistic selection. These results predict an interesting mismatch between molecular population genetic and quantitative genetic patterns of variation. Balanced, antagonistically selected alleles are expected to contribute more to additive genetic variance for fitness than alleles maintained by classic, nonantagonistic mechanisms. Nevertheless, classical mechanisms of balancing selection are much more likely to generate strong population genetic signatures of recent balancing selection.

WOLBACHIA INFECTION AND DRAMATIC INTRASPECIFIC MITOCHONDRIAL DNA DIVERGENCE IN A FIG WASP

Mitochondria and Wolbachia are maternally inherited genomes that exhibit strong linkage disequilibrium in many organisms. We surveyed Wolbachia infections in 187 specimens of the fig wasp species, Ceratosolen solmsi, and found an infection prevalence of 89.3%. DNA sequencing of 20 individuals each from Wolbachia-infected and -uninfected subpopulations revealed extreme mtDNA divergence (up to 9.2% and 15.3% in CO1 and cytochrome b, respectively) between infected and uninfected wasps. Further, mtDNA diversity was significantly reduced within the infected group. Our sequencing of a large part of the mitochondrial genome from both Wolbachia-infected and -uninfected individuals revealed that high sequence divergence is common throughout the mitochondrial genome. These patterns suggest a partial selective sweep of mitochondria subsequent to the introduction of Wolbachia into C. solsmi, by hybrid introgression from a related species.

Revisiting protein heterozygosity in plants—nucleotide diversity in allozyme coding genes of conifer Pinus sylvestris

Allozyme variation has been and continues to be a major source of information on the level of genetic variation among plant species. Deciphering the molecular basis of electrophoretic variation is essential for understanding the forces affecting the protein level variation. In this study, the relationship between allozyme heterozygosity and nucleotide diversity in plants is investigated among and within species. Allozyme and nucleotide diversity in 27 plant species was reviewed. At the multilocus level, the two methods are congruent: a clear correlation between the two measures of genetic diversity among plant species was observed, strengthening the view that effective population size is the major determinant of genome-wide diversity. Nucleotide diversity at six allozyme coding genes (6pgdB, aco, gdh, gotC, mdhA, and mdhB) in conifer Pinus sylvestris was investigated jointly with electrophoretic data. Single non-synonymous charge-changing mutations were found together with electrophoretic alleles that consequently were mutationally unique. Synonymous site nucleotide diversity (point estimate of θW—0.009 per bp) and silent site divergence from Pinus pinaster at allozyme coding loci were at comparable levels with other loci in the species. Linkage disequilibrium was extensive compared to earlier estimates from P. sylvestris and other trees, spanning several kilobases. Allozyme coding genes had an excess of closely related haplotypes whose frequency has recently increased possibly as a result of partial selective sweeps or balancing selection, but complex demographic effects cannot be excluded.

Haplotype Structure and Expression Divergence at the Drosophila Cellular Immune Gene eater

The protein Eater plays an important role in microbial recognition and defensive phagocytosis in Drosophila melanogaster. We sequenced multiple alleles of the eater gene from an African and a North American population of D. melanogaster and found signatures of a partial selective sweep in North America that is localized around the second intron. This pattern is consistent with local adaptation to novel selective pressures during range expansion out of Africa. The North American sample is divided into two predominant haplotype groups, and the putatively selected haplotype is associated with a significantly higher gene expression level, suggesting that gene regulation is a possible target of selection. The eater alleles contain from 22 to 40 repeat units that are characterized by the presence of a cysteine-rich NIM motif. NIM repeats in the structural stalk of the protein exhibit concerted evolution as a function of physical location in the repeat array. Several NIM repeats within eater have previously been implicated in binding to microbial ligands, a function which in principle might subject them to special evolutionary pressures. However, we find no evidence of elevated positive selection on these pathogen-interacting units. Our study presents an instance where gene expression rather than protein structure is thought to drive the adaptive evolution of a pathogen recognition molecule in the immune system.

ADAPTATION TO DIFFERENT RATES OF ENVIRONMENTAL CHANGE INCHLAMYDOMONAS

We investigate how different rates of environmental change affect adaptive outcomes and dynamics by selecting Chlamydomonas populations for over 200 generations in environments where the rate of change varies. We find that slower rates of environmental change result in end populations that grow faster and pay a lower cost of adaptation than populations that adapt to a sudden change of the same magnitude. We detected partial selective sweeps in adapting populations by monitoring changes in marker frequency in each population. Although populations adapting to a sudden environmental change showed evidence of mutations of large effect segregating early on, populations adapting to slow rates of change showed patterns that were consistent with mutations of relatively small effect occurring at less predictable times. This work suggests that rates of environmental change may fundamentally alter adaptive dynamics and outcomes of adaptation by changing the size and timing of fitness increases. We suggest that using mutations of smaller effect during adaptation may result in lower levels of pleiotropy and historical constraints, which could in turn result in higher fitness by the end of the experiment.

Molecular signature of epistatic selection: interrogating genetic interactions in thesex-ratiomeiotic drive ofDrosophila simulans

Fine scale analyses of signatures of selection allow assessing quantitative aspects of a species' evolutionary genetic history, such as the strength of selection on genes. When several selected loci lie in the same genomic region, their epistatic interactions may also be investigated. Here, we study how the neutral polymorphism pattern was shaped by two close recombining loci that cause 'sex-ratio' meiotic drive in Drosophila simulans, as an example of strong selection with potentially strong epistasis. We compare the polymorphism data observed in a natural population with the results of forward stochastic simulations under several contexts of epistasis between the candidate loci for the drive. We compute the likelihood of different possible scenarios, in order to determine which configuration is most consistent with the data. Our results highlight that fine scale analyses of well-chosen candidate genomic regions provide information-rich data that can be used to investigate the genotype-phenotype-fitness map, which can hardly be studied in genome-wide analyses. We also emphasize that initial conditions and time of observation (here, time after the interruption of a partial selective sweep) are crucial parameters in the interpretation of real data, while these are often overlooked in theoretical studies.

High Rate of Recent Transposable Element–Induced Adaptation in Drosophila melanogaster

Although transposable elements (TEs) are known to be potent sources of mutation, their contribution to the generation of recent adaptive changes has never been systematically assessed. In this work, we conduct a genome-wide screen for adaptive TE insertions in Drosophila melanogaster that have taken place during or after the spread of this species out of Africa. We determine population frequencies of 902 of the 1,572 TEs in Release 3 of the D. melanogaster genome and identify a set of 13 putatively adaptive TEs. These 13 TEs increased in population frequency sharply after the spread out of Africa. We argue that many of these TEs are in fact adaptive by demonstrating that the regions flanking five of these TEs display signatures of partial selective sweeps. Furthermore, we show that eight out of the 13 putatively adaptive elements show population frequency heterogeneity consistent with these elements playing a role in adaptation to temperate climates. We conclude that TEs have contributed considerably to recent adaptive evolution (one TE-induced adaptation every 200–1,250 y). The majority of these adaptive insertions are likely to be involved in regulatory changes. Our results also suggest that TE-induced adaptations arise more often from standing variants than from new mutations. Such a high rate of TE-induced adaptation is inconsistent with the number of fixed TEs in the D. melanogaster genome, and we discuss possible explanations for this discrepancy.

Low Levels of Polymorphism in Genes That Control the Activation of Defense Response inArabidopsis thaliana

Plants use signaling pathways involving salicylic acid, jasmonic acid, and ethylene to defend against pathogen and herbivore attack. Many defense response genes involved in these signaling pathways have been characterized, but little is known about the selective pressures they experience. A representative set of 27 defense response genes were resequenced in a worldwide set of 96 Arabidopsis thaliana accessions, and patterns of single nucleotide polymorphisms (SNPs) were evaluated in relation to an empirical distribution of SNPs generated from either 876 fragments or 236 fragments with >400 bp coding sequence (this latter set was selected for comparisons with coding sequences) distributed across the genomes of the same set of accessions. Defense response genes have significantly fewer protein variants, display lower levels of nonsynonymous nucleotide diversity, and have fewer nonsynonymous segregating sites. The majority of defense response genes appear to be experiencing purifying selection, given the dearth of protein variation in this set of genes. Eight genes exhibit some evidence of partial selective sweeps or transient balancing selection. These results therefore provide a strong contrast to the high levels of balancing selection exhibited by genes at the upstream positions in these signaling pathways.

Nonadaptive Explanations for Signatures of Partial Selective Sweeps in Drosophila

A beneficial mutation that has nearly but not yet fixed in a population produces a characteristic haplotype configuration, called a partial selective sweep. Whether nonadaptive processes might generate similar haplotype configurations has not been extensively explored. Here, we consider 5 population genetic data sets taken from regions flanking high-frequency transposable elements in North American strains of Drosophila melanogaster, each of which appears to be consistent with the expectations of a partial selective sweep. We use coalescent simulations to explore whether incorporation of the species' demographic history, purifying selection against the element, or suppression of recombination caused by the element could generate putatively adaptive haplotype configurations. Whereas most of the data sets would be rejected as nonneutral under the standard neutral null model, only the data set for which there is strong external evidence in support of an adaptive transposition appears to be nonneutral under the more complex null model and in particular when demography is taken into account. High-frequency, derived mutations from a recently bottlenecked population, such as we study here, are of great interest to evolutionary genetics in the context of scans for adaptive events; we discuss the broader implications of our findings in this context.

Unusual pattern of single nucleotide polymorphism at the exuperantia2 locus of Drosophila pseudoobscura.

We have investigated the pattern of DNA sequence variation at the exuperantia2 locus in Drosophila pseudoobscura. This adds to the increasing dataset of genetic variation in D. pseudoobscura, a useful model species for evolutionary genetic studies. The level of silent site nucleotide diversity and the divergence from an outgroup Drosophila miranda are comparable with those for other X-linked loci. One peculiar pattern at the exu2 locus of D. pseudoobscura is a complete linkage disequilibrium between two SNPs, one of which is a replacement site. As a result, there are two distinct haplotype groups in our dataset. Based upon the comparisons with the outgroup sequences from D. miranda and Drosophila persimilis, we show that the newly derived haplotype group has lower diversity than the ancestral haplotype group. The pattern of protein evolution at exu2 shows some deviation from the neutral model. Together, these and other characteristics of the exu2 locus suggest the action of selection on the pattern of SNP variation, consistent with a partial selective sweep associated with the newly derived haplotype.

Effect of inversion polymorphism on the neutral nucleotide variability of linked chromosomal regions in Drosophila.

Recombination is a main factor determining nucleotide variability in different regions of the genome. Chromosomal inversions, which are ubiquitous in the genus Drosophila, are known to reduce and redistribute recombination, and thus their specific effect on nucleotide variation may be of major importance as an explanatory factor for levels of DNA variation. Here, we use the coalescent approach to study this effect. First, we develop analytical expressions to predict nucleotide variability in old inversion polymorphisms that have reached mutation-drift-flux equilibrium. The effects on nucleotide variability of a new arrangement appearing in the population and reaching a stable polymorphism are then studied by computer simulation. We show that inversions modulate nucleotide variability in a complex way. The establishment of an inversion polymorphism involves a partial selective sweep that eliminates part of the variability in the population. This is followed by a slow convergence to the equilibrium values. During this convergence, regions close to the breakpoints exhibit much lower variability than central regions. However, at equilibrium, regions close to the breakpoints have higher levels of variability and differentiation between arrangements than regions in the middle of the inverted segment. The implications of these findings for overall variability levels during the evolution of Drosophila species are discussed.