Hard Selective Sweep Research Articles

Distinct types of selection and genetic architecture shape molecular variation during the domestication of vegetable crops.

Humans select vegetable crops with desirable traits via a complex evolutionary process called domestication, generating a variety of cultivars worldwide. With advances in sequencing technologies, genomic scans for "signatures of selection" are widely used to identify target loci of selection. In the early phases of domestication, humans tended to favor similar sets of phenotypes in diverse crops, resulting in "domestication syndrome" and parallel evolution in multiple species. Subsequently, adaptation to distinct environments or different consumer preferences has diversified crop cultivars. Here, we review molecular and population genetic studies on genes affecting trait evolution during this complex process. We emphasize that, depending on interactions among different types of selection (directional selection within or divergent selection between groups), the genetic architecture of the target trait (Mendelian or polygenic), and the origin of the causal variant (new mutation or standing variation), the resulting molecular patterns of variation can be highly diverse. Situations in which the typical hard selective sweep model could be applied may be limited. Therefore, it is crucial to obtain a thorough understanding of the target species' historical, environmental, and ecological contexts.

Evolutionary origin and distribution of amino acid mutations associated with resistance to sodium channel modulators in onion thrips, Thrips tabaci

In onion thrips Thrips tabaci, reduced sensitivity of the sodium channel caused by several sodium channel mutations have been correlated with pyrethroid resistance. For this study, using mitochondrial cytochrome c oxidase subunit I gene sequences, we examined the phylogenetic relation among a total of 52 thelytokous and arrhenotokous strains with different genotypes of the sodium channel mutations. Then, we used flow cytometry to estimate their ploidy. Results showed that the strains are divisible into three groups: diploid thelytoky, triploid thelytoky, and diploid arrhenotoky. Using 23 whole genome resequencing data obtained from 20 strains out of 52, we examined their genetic relation further using principal component analysis, admixture analysis, and a fixation index. Results showed that diploid and triploid thelytokous groups are further classifiable into two based on the sodium channel mutations harbored by the respective group members (strains). The greatest genetic divergence was observed between thelytokous and arrhenotokous groups with a pair of T929I and K1774N. Nevertheless, they shared a genomic region with virtually no polymorphism around the sodium channel gene loci, suggesting a hard selective sweep. Based on these findings, we discuss the evolutionary origin and distribution of the sodium channel mutations in T. tabaci.

Demographic history and distinct selection signatures of two domestication genes in mungbean.

Domestication is the long and complex process underlying the evolution of crops, in which artificial directional selection transformed wild progenitors into the desired form, affecting genomic variation and leaving traces of selection at targeted loci. However, whether genes controlling important domestication traits follow the same evolutionary pattern expected under the standard selective sweep model remains unclear. With whole-genome re-sequencing of mungbean (Vigna radiata), we investigated this issue by resolving its global demographic history and targeted dissection of the molecular footprints of genes underlying two key traits representing different stages of domestication. Mungbean originated in Asia, and the Southeast Asian wild population migrated to Australia about 50 thousand generations ago (kga). Later in Asia, the cultivated form diverged from the wild progenitor. We identified the gene associated with the pod shattering resistance trait, VrMYB26a, with lower expression across cultivars and reduced polymorphism in the promoter region, reflecting a hard selective sweep. On the other hand, the stem determinacy trait was associated with VrDet1. We found two ancient haplotypes of this gene have lower gene expression and exhibited intermediate frequencies in cultivars, consistent with selection favoring independent haplotypes in a soft selective sweep. In mungbean, contrasting signatures of selection were identified from the detailed dissection of two important domestication traits. The results suggest complex genetic architecture underlying the seemingly simple process of directional artificial selection and highlight the limitations of genome-scan methods relying on hard selective sweeps.

Evidence of hard-selective sweeps suggests independent adaptation to insecticides in Colorado potato beetle (Coleoptera: Chrysomelidae) populations.

Pesticide resistance provides one of the best examples of rapid evolution to environmental change. The Colorado potato beetle (CPB) has a long and noteworthy history as a super-pest due to its ability to repeatedly develop resistance to novel insecticides and rapidly expand its geographic and host plant range. Here, we investigate regional differences in demography, recombination, and selection using whole-genome resequencing data from two highly resistant CPB populations in the United States (Hancock, Wisconsin and Long Island, New York). Demographic reconstruction corroborates historical records for a single pest origin during the colonization of the Midwestern and Eastern United States in the mid- to late-19th century and suggests that the effective population size might be higher in Long Island, NY than Hancock, WI despite contemporary potato acreage of Wisconsin being far greater. Population-based recombination maps show similar background recombination rates between these populations, as well as overlapping regions of low recombination that intersect with important metabolic detoxification genes. In both populations, we find compelling evidence for hard selective sweeps linked to insecticide resistance with multiple sweeps involving genes associated with xenobiotic metabolism, stress response, and defensive chemistry. Notably, only two candidate insecticide resistance genes are shared among both populations, but both appear to be independent hard selective sweep events. This suggests that repeated, rapid, and independent evolution of genes may underlie CPB's pest status among geographically distinct populations.

A two-step adaptive walk rewires nutrient transport in a challenging edaphic environment.

Most well-characterized cases of adaptation involve single genetic loci. Theory suggests that multilocus adaptive walks should be common, but these are challenging to identify in natural populations. Here, we combine trait mapping with population genetic modeling to show that a two-step process rewired nutrient homeostasis in a population of Arabidopsis as it colonized the base of an active stratovolcano characterized by extremely low soil manganese (Mn). First, a variant that disrupted the primary iron (Fe) uptake transporter gene (IRT1) swept quickly to fixation in a hard selective sweep, increasing Mn but limiting Fe in the leaves. Second, multiple independent tandem duplications occurred at NRAMP1 and together rose to near fixation in the island population, compensating the loss of IRT1 by improving Fe homeostasis. This study provides a clear case of a multilocus adaptive walk and reveals how genetic variants reshaped a phenotype and spread over space and time.

Genomes reveal selective sweeps in kiang and donkey for high-altitude adaptation.

Over the last several hundred years, donkeys have adapted to high-altitude conditions on the Tibetan Plateau. Interestingly, the kiang, a closely related equid species, also inhabits this region. Previous reports have demonstrated the importance of specific genes and adaptive introgression in divergent lineages for adaptation to hypoxic conditions on the Tibetan Plateau. Here, we assessed whether donkeys and kiangs adapted to the Tibetan Plateau via the same or different biological pathways and whether adaptive introgression has occurred. We assembled a de novo genome from a kiang individual and analyzed the genomes of five kiangs and 93 donkeys (including 24 from the Tibetan Plateau). Our analyses suggested the existence of a strong hard selective sweep at the EPAS1 locus in kiangs. In Tibetan donkeys, however, another gene, i.e., EGLN1, was likely involved in their adaptation to high altitude. In addition, admixture analysis found no evidence for interspecific gene flow between kiangs and Tibetan donkeys. Our findings indicate that despite the short evolutionary time scale since the arrival of donkeys on the Tibetan Plateau, as well as the existence of a closely related species already adapted to hypoxia, Tibetan donkeys did not acquire adaptation via admixture but instead evolved adaptations via a different biological pathway.

The evolutionary genetics of lactase persistence in seven ethnic groups across the Iranian plateau

BackgroundThe ability to digest dietary lactose is associated with lactase persistence (LP) in the intestinal lumen in human. The genetic basis of LP has been investigated in many populations in the world. Iran has a long history of pastoralism and the daily consumption of dairy products; thus, we aim to assess how LP has evolved in the Iranian population. We recruited 400 adult individuals from seven Iranian ethnic groups, from whom we investigated their lactose tolerance and screened the genetic variants in their lactase gene locus.ResultsThe LP frequency distribution ranged from 0 to 29.9% in the seven Iranian ethnic groups with an average value of 9.8%. The variants, − 13910*T and − 22018*A, were significantly associated with LP phenotype in Iranians. We found no evidence of hard selective sweep for − 13910*T and − 22018*A in Persians, the largest ethnic group of Iran. The extremely low frequency of − 13915*G in the Iranian population challenged the view that LP distribution in Iran resulted from the demic diffusion, especially mediated by the spread of Islam, from the Arabian Peninsula.ConclusionsOur results indicate the distribution of LP in seven ethnic groups across the Iranian plateau. Soft selective sweep rather than hard selective sweep played a substantial role in the evolution of LP in Iranian populations.

PRDM9 and the evolution of recombination hotspots

Recombination in mammals is not uniformly distributed along the chromosome but concentrated in small regions known as recombination hotspots. Recombination starts with the double-strand break of a chromosomal sequence and results in the transmission of the sequence that does not break (preventing recombination) more often than the sequence that breaks (allowing recombination). Thus recombination itself renders individual recombination hotspots inactive and over time should drive them to extinction in the genome. Empirical evidence shows that individual recombination hotspots die but, far from being driven to extinction, they are abundant in the genome: a contradiction referred to as the Recombination Hotspot Paradox. What saves recombination hotspots from extinction? The current answer relies in the formation of new recombination hotspots in new genomic sites driven by viability selection in favor of recombination. Here we formulate a population genetics model that incorporates the molecular mechanism initiating recombination in mammals (PRDM9-like genes), to provide an alternative solution to the paradox. We find that weak selection allows individual recombination hotspots to become inactive (die) while saving them from extinction in the genome by driving their re-activation (resurrection). Our model shows that when selection for recombination is weak, the introduction of rare variants causes recombination sites to oscillate between hot and cold phenotypes with a recombination hotspot dying only to come back. Counter-intuitively, we find that low viability selection leaves a hard selective sweep signature in the genome, with the selective sweep at the recombination hotspot being the hardest when viability selection is the lowest. Our model can help to understand the rapid evolution of PRDM9, the co-existence of two types of hotspots, the life expectancy of hotspots, and the volatility of the recombinational landscape (with hotspots rarely being shared between closely related species).

McSwan: A joint site frequency spectrum method to detect and date selective sweeps across multiple population genomes.

Inferring the mode and tempo of natural selection helps further our understanding of adaptation to past environmental changes. Here, we introduce McSwan, a method to detect and date past and recent natural selection events in the case of a hard sweep. The method is based on the comparison of site frequency spectra obtained under various demographic models that include selection. McSwan demonstrated high power (high sensitivity and specificity) in capturing hard selective sweep events without requiring haplotype phasing. It performed slightly better than SweeD when the recent effective population size was low and the genomic region was small. We then applied our method to a European (CEU) and an African (LWK) human re-sequencing data set. Most hard sweeps were detected in the CEU population (96%). Moreover, hard sweeps in the African population were estimated to have occurred further back in time (mode: 43,625years BP) compared to those of Europeans (mode: 24,850years BP). Most of the estimated ages of hard sweeps in Europeans were associated with the Last Glacial Maximum and were enriched in immunity-associated genes.

Detection and Classification of Hard and Soft Sweeps from Unphased Genotypes by Multilocus Genotype Identity.

Positive natural selection can lead to a decrease in genomic diversity at the selected site and at linked sites, producing a characteristic signature of elevated expected haplotype homozygosity. These selective sweeps can be hard or soft. In the case of a hard selective sweep, a single adaptive haplotype rises to high population frequency, whereas multiple adaptive haplotypes sweep through the population simultaneously in a soft sweep, producing distinct patterns of genetic variation in the vicinity of the selected site. Measures of expected haplotype homozygosity have previously been used to detect sweeps in multiple study systems. However, these methods are formulated for phased haplotype data, typically unavailable for nonmodel organisms, and some may have reduced power to detect soft sweeps due to their increased genetic diversity relative to hard sweeps. To address these limitations, we applied the H12 and H2/H1 statistics proposed in 2015 by Garud et al., which have power to detect both hard and soft sweeps, to unphased multilocus genotypes, denoting them as G12 and G2/G1. G12 (and the more direct expected homozygosity analog to H12, denoted G123) has comparable power to H12 for detecting both hard and soft sweeps. G2/G1 can be used to classify hard and soft sweeps analogously to H2/H1, conditional on a genomic region having high G12 or G123 values. The reason for this power is that, under random mating, the most frequent haplotypes will yield the most frequent multilocus genotypes. Simulations based on parameters compatible with our recent understanding of human demographic history suggest that expected homozygosity methods are best suited for detecting recent sweeps, and increase in power under recent population expansions. Finally, we find candidates for selective sweeps within the 1000 Genomes CEU, YRI, GIH, and CHB populations, which corroborate and complement existing studies.

New insights into global biogeography, population structure and natural selection from the genome of the epipelagic copepod Oithona.

In the epipelagic ocean, the genus Oithona is considered as one of the most abundant and widespread copepods and plays an important role in the trophic food web. Despite its ecological importance, little is known about Oithona and cyclopoid copepods genomics. Therefore, we sequenced, assembled and annotated the genome of Oithona nana. The comparative genomic analysis integrating available copepod genomes highlighted the expansions of genes related to stress response, cell differentiation and development, including genes coding Lin12-Notch-repeat (LNR) domain proteins. The Oithona biogeography based on 28S sequences and metagenomic reads from the Tara Oceans expedition showed the presence of O.nana mostly in the Mediterranean Sea (MS) and confirmed the amphitropical distribution of Oithona similis. The population genomics analyses of O.nana in the Northern MS, integrating the Tara Oceans metagenomic data and the O.nana genome, led to the identification of genetic structure between populations from the MS basins. Furthermore, 20 loci were found to be under positive selection including four missense and eight synonymous variants, harbouring soft or hard selective sweep patterns. One of the missense variants was localized in the LNR domain of the coding region of a male-specific gene. The variation in the B-allele frequency with respect to the MS circulation pattern showed the presence of genomic clines between O.nana and another undefined Oithona species possibly imported through Atlantic waters. This study provides new approaches and results in zooplankton population genomics through the integration of metagenomic and oceanographic data.

Genealogies of two linked neutral loci after a selective sweep in a large population of stochastically varying size

Abstract We study the impact of a hard selective sweep on the genealogy of partially linked neutral loci in the vicinity of the positively selected allele. We consider a sexual population of stochastically varying size and, focusing on two neighboring loci, derive an approximate formula for the neutral genealogy of a sample of individuals taken at the end of the sweep. Individuals are characterized by ecological parameters depending on their genetic type, and governing their growth rate and interactions with other individuals (competition). As a consequence, the `fitness' of an individual depends on the population state and is not an intrinsic characteristic of individuals. We provide a deep insight into the dynamics of the mutant and wild-type populations during the different stages of a selective sweep.

The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study

SummaryBackgroundEvidence suggests that the PfKelch13 mutations that confer artemisinin resistance in falciparum malaria have multiple independent origins across the Greater Mekong subregion, which has motivated a regional malaria elimination agenda. We aimed to use molecular genotyping to assess antimalarial drug resistance selection and spread in the Greater Mekong subregion.MethodsIn this observational study, we tested Plasmodium falciparum isolates from Myanmar, northeastern Thailand, southern Laos, and western Cambodia for PfKelch13 mutations and for Pfplasmepsin2 gene amplification (indicating piperaquine resistance). We collected blood spots from patients with microscopy or rapid test confirmed uncomplicated falciparum malaria. We used microsatellite genotyping to assess genetic relatedness.FindingsAs part of studies on the epidemiology of artemisinin-resistant malaria between Jan 1, 2008, and Dec 31, 2015, we collected 434 isolates. In 2014–15, a single long PfKelch13 C580Y haplotype (−50 to +31·5 kb) lineage, which emerged in western Cambodia in 2008, was detected in 65 of 88 isolates from northeastern Thailand, 86 of 111 isolates from southern Laos, and 14 of 14 isolates from western Cambodia, signifying a hard transnational selective sweep. Pfplasmepsin2 amplification occurred only within this lineage, and by 2015 these closely related parasites were found in ten of the 14 isolates from Cambodia and 15 of 15 isolates from northeastern Thailand. C580Y mutated parasites from Myanmar had a different genetic origin.InterpretationOur results suggest that the dominant artemisinin-resistant P falciparum C580Y lineage probably arose in western Cambodia and then spread to Thailand and Laos, outcompeting other parasites and acquiring piperaquine resistance. The emergence and spread of fit artemisinin-resistant P falciparum parasite lineages, which then acquire partner drug resistance across the Greater Mekong subregion, threatens regional malaria control and elimination goals. Elimination of falciparum malaria from this region should be accelerated while available antimalarial drugs still remain effective.FundingThe Wellcome Trust and the Bill and Melinda Gates Foundation.

More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1.

In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.

The Genomic Basis of Postponed Senescence in Drosophila melanogaster.

Natural populations harbor considerable genetic variation for lifespan. While evolutionary theory provides general explanations for the existence of this variation, our knowledge of the genes harboring naturally occurring polymorphisms affecting lifespan is limited. Here, we assessed the genetic divergence between five Drosophila melanogaster lines selected for postponed senescence for over 170 generations (O lines) and five lines from the same base population maintained at a two week generation interval for over 850 generations (B lines). On average, O lines live 70% longer than B lines, are more productive at all ages, and have delayed senescence for other traits than reproduction. We performed population sequencing of pools of individuals from all B and O lines and identified 6,394 genetically divergent variants in or near 1,928 genes at a false discovery rate of 0.068. A 2.6 Mb region at the tip of the X chromosome contained many variants fixed for alternative alleles in the two populations, suggestive of a hard selective sweep. We also assessed genome wide gene expression of O and B lines at one and five weeks of age using RNA sequencing and identified genes with significant (false discovery rate < 0.05) effects on gene expression with age, population and the age by population interaction, separately for each sex. We identified transcripts that exhibited the transcriptional signature of postponed senescence and integrated the gene expression and genetic divergence data to identify 98 (175) top candidate genes in females (males) affecting postponed senescence and increased lifespan. While several of these genes have been previously associated with Drosophila lifespan, most are novel and constitute a rich resource for future functional validation.

Recent selective sweeps in North American Drosophila melanogaster show signatures of soft sweeps.

Adaptation from standing genetic variation or recurrent de novo mutation in large populations should commonly generate soft rather than hard selective sweeps. In contrast to a hard selective sweep, in which a single adaptive haplotype rises to high population frequency, in a soft selective sweep multiple adaptive haplotypes sweep through the population simultaneously, producing distinct patterns of genetic variation in the vicinity of the adaptive site. Current statistical methods were expressly designed to detect hard sweeps and most lack power to detect soft sweeps. This is particularly unfortunate for the study of adaptation in species such as Drosophila melanogaster, where all three confirmed cases of recent adaptation resulted in soft selective sweeps and where there is evidence that the effective population size relevant for recent and strong adaptation is large enough to generate soft sweeps even when adaptation requires mutation at a specific single site at a locus. Here, we develop a statistical test based on a measure of haplotype homozygosity (H12) that is capable of detecting both hard and soft sweeps with similar power. We use H12 to identify multiple genomic regions that have undergone recent and strong adaptation in a large population sample of fully sequenced Drosophila melanogaster strains from the Drosophila Genetic Reference Panel (DGRP). Visual inspection of the top 50 candidates reveals that in all cases multiple haplotypes are present at high frequencies, consistent with signatures of soft sweeps. We further develop a second haplotype homozygosity statistic (H2/H1) that, in combination with H12, is capable of differentiating hard from soft sweeps. Surprisingly, we find that the H12 and H2/H1 values for all top 50 peaks are much more easily generated by soft rather than hard sweeps. We discuss the implications of these results for the study of adaptation in Drosophila and in species with large census population sizes.

Hard selective sweep and ectopic gene conversion in a gene cluster affording environmental adaptation.

Among the rare colonizers of heavy-metal rich toxic soils, Arabidopsis halleri is a compelling model extremophile, physiologically distinct from its sister species A. lyrata, and A. thaliana. Naturally selected metal hypertolerance and extraordinarily high leaf metal accumulation in A. halleri both require Heavy Metal ATPase4 (HMA4) encoding a PIB-type ATPase that pumps Zn2+ and Cd2+ out of specific cell types. Strongly enhanced HMA4 expression results from a combination of gene copy number expansion and cis-regulatory modifications, when compared to A. thaliana. These findings were based on a single accession of A. halleri. Few studies have addressed nucleotide sequence polymorphism at loci known to govern adaptations. We thus sequenced 13 DNA segments across the HMA4 genomic region of multiple A. halleri individuals from diverse habitats. Compared to control loci flanking the three tandem HMA4 gene copies, a gradual depletion of nucleotide sequence diversity and an excess of low-frequency polymorphisms are hallmarks of positive selection in HMA4 promoter regions, culminating at HMA4-3. The accompanying hard selective sweep is segmentally eclipsed as a consequence of recurrent ectopic gene conversion among HMA4 protein-coding sequences, resulting in their concerted evolution. Thus, HMA4 coding sequences exhibit a network-like genealogy and locally enhanced nucleotide sequence diversity within each copy, accompanied by lowered sequence divergence between paralogs in any given individual. Quantitative PCR corroborated that, across A. halleri, three genomic HMA4 copies generate overall 20- to 130-fold higher transcript levels than in A. thaliana. Together, our observations constitute an unexpectedly complex profile of polymorphism resulting from natural selection for increased gene product dosage. We propose that these findings are paradigmatic of a category of multi-copy genes from a broad range of organisms. Our results emphasize that enhanced gene product dosage, in addition to neo- and sub-functionalization, can account for the genomic maintenance of gene duplicates underlying environmental adaptation.