HaploBlocks: Efficient Detection of Positive Selection in Large Population Genomic Datasets

Genomic regions under positive selection harbor variation linked for example to adaptation. Most tools for detecting positively selected variants have computational resource requirements rendering them impractical on population genomic datasets with hundreds of thousands of individuals or more. We have developed and implemented an efficient haplotype-based approach able to scan large datasets and accurately detect positive selection. We achieve this by combining a pattern matching approach based on the positional Burrows–Wheeler transform with model-based inference which only requires the evaluation of closed-form expressions. We evaluate our approach with simulations, and find it to be both sensitive and specific. The computational resource requirements quantified using UK Biobank data indicate that our implementation is scalable to population genomic datasets with millions of individuals. Our approach may serve as an algorithmic blueprint for the era of “big data” genomics: a combinatorial core coupled with statistical inference in closed form.     

Unbroken: RADseq remains a powerful tool for understanding the genetics of adaptation in natural populations

Recently, Lowry et al. addressed the ability of RADseq approaches to detect loci under selection in genome scans. While the authors raise important considerations, such as accounting for the extent of linkage disequilibrium in a study system, we strongly disagree with their overall view of the ability of RADseq to inform our understanding of the genetic basis of adaptation. The family of RADseq protocols has radically improved the field of population genomics, expanding by several orders of magnitude the number of markers available while substantially reducing the cost per marker. Researchers whose goal is to identify regions of the genome under selection must consider the LD of the experimental system; however, there is no magical LD cutoff below which researchers should refuse to use RADseq. Lowry et al. further made two major arguments: a theoretical argument that modeled the likelihood of detecting selective sweeps with RAD markers, and gross summaries based on an anecdotal collection of RAD studies. Unfortunately, their simulations were off by two orders of magnitude in the worst case, while their anecdotes merely showed that it is possible to get widely divergent densities of RAD tags for any particular experiment, either by design or due to experimental efficacy. We strongly argue that RADseq remains a powerful and efficient approach that provides sufficient marker density for studying selection in many natural populations. Given limited resources, we argue that researchers should consider a wide range of trade‐offs among genomic techniques, in light of their study question and the power of different techniques to answer it.     

Responsible RAD: Striving for best practices in population genomic studies of adaptation

Two recent articles were written in response to our paper “Breaking RAD: An evaluation of the utility of restriction site associated DNA sequencing scans of adaptation.” While we agree with some of the comments made by the authors of these two response papers, we still believe caution should be employed in RADseq studies that aim to detect loci that contribute to adaptation. In this rebuttal, we evaluate the key points made in these papers, attempt to identify a middle ground and make suggestions for responsibly conducting future studies to understand the genomewide mechanisms of adaptation.     

Molecular signatures of lineage‐specific adaptive evolution in a unique sea basin: the example of an anadromous goby Leucopsarion petersii

Climate changes on various time scales often shape genetic novelty and adaptive variation in many biotas. We explored molecular signatures of directional selection in populations of the ice goby Leucopsarion petersii inhabiting a unique sea basin, the Sea of Japan, where a wide variety of environments existed in the Pleistocene in relation to shifts in sea level by repeated glaciations. This species consisted of two historically allopatric lineages, the Japan Sea (JS) and Pacific Ocean (PO) lineages, and these have lived under contrasting marine environments that are expected to have imposed different selection regimes caused by past climatic and current oceanographic factors. We applied a limited genome‐scan approach using seven candidate genes for phenotypic differences between two lineages in combination with 100 anonymous microsatellite loci. Neuropeptide Y (NPY) gene, which is an important regulator of food intake and potent orexigenic agent, and three anonymous microsatellites were identified as robust outliers, that is, candidate loci potentially under directional selection, by multiple divergence‐ and diversity‐based outlier tests in comparisons focused on multiple populations of the JS vs. PO lineages. For these outlier loci, populations of the JS lineage had putative signals of selective sweeps. Additionally, real‐time quantitative PCR analysis using fish reared in a common environment showed a higher expression level for NPY gene in the JS lineage. Thus, this study succeeded in identifying candidate genomic regions under selection across populations of the JS lineage and provided evidence for lineage‐specific adaptive evolution in this unique sea basin.     

An assessment of the spatial scale of local adaptation in brown trout (Salmo trutta L.): footprints of selection at microsatellite DNA loci

Local adaptation is considered a paradigm in studies of salmonid fish populations. Yet, little is known about the geographical scale of local adaptation. Is adaptive divergence primarily evident at the scale of regions or individual populations? Also, many salmonid populations are subject to spawning intrusion by farmed conspecifics that experience selection regimes fundamentally different from wild populations. This prompts the question if adaptive differences between wild populations and hatchery strains are more pronounced than between different wild populations? We addressed these issues by analyzing variation at 74 microsatellite loci (including anonymous and expressed sequence tag- and quantitative trait locus-linked markers) in 15 anadromous wild brown trout (Salmo trutta L.) populations, representing five geographical regions, along with two lake populations and two hatchery strains used for stocking some of the populations. F_ST-based outlier tests revealed more outlier loci between different geographical regions separated by 522±228 km (mean±s.d.) than between populations within regions separated by 117±79 km (mean±s.d.). A significant association between geographical distance and number of outliers between regions was evident. There was no evidence for more outliers in comparisons involving hatchery trout, but the loci under putative selection generally were not the same as those found to be outliers between wild populations. Our study supports the notion of local adaption being increasingly important at the scale of regions as compared with individual populations, and suggests that loci involved in adaptation to captive environments are not necessarily the same as those involved in adaptive divergence among wild populations.     

Spatial analysis method (sam): a software tool combining molecular and environmental data to identify candidate loci for selection

sam is a Windows program designed to detect candidate loci for selection in whole-genome scans. It also gives valuable clues as regards the ecological factors at stake in the selection process. The method used is based on multiple univariate logistic regression models to test for association between allelic frequencies at marker loci and environmental variables. The software reads matrices constituted of presence/absence of molecular markers, and of the corresponding environmental parameters at sampling locations. It provides dynamic analysis tables to process the results. The tool is freely available for download at http://www.econogene.eu/software/sam/.     

Genetic association with high‐resolution climate data reveals selection footprints in the genomes of barley landraces across the Iberian Peninsula

Landraces are local populations of crop plants adapted to a particular environment. Extant landraces are surviving genetic archives, keeping signatures of the selection processes experienced by them until settling in their current niches. This study intends to establish relationships between genetic diversity of barley (Hordeum vulgare L.) landraces collected in Spain and the climate of their collection sites. A high‐resolution climatic data set (5 × 5 km spatial, 1‐day temporal grid) was computed from over 2,000 temperature and 7,000 precipitation stations across peninsular Spain. This data set, spanning the period 1981–2010, was used to derive agroclimatic variables meaningful for cereal production at the collection sites of 135 barley landraces. Variables summarize temperature, precipitation, evapotranspiration, potential vernalization and frost probability at different times of the year and time scales (season and month). SNP genotyping of the landraces was carried out combining Illumina Infinium assays and genotyping‐by‐sequencing, yielding 9,920 biallelic markers (7,479 with position on the barley reference genome). The association of these SNPs with agroclimatic variables was analysed at two levels of genetic diversity, with and without taking into account population structure. The whole data sets and analysis pipelines are documented and available at https://eead-csic-compbio.github.io/barley-agroclimatic-association . We found differential adaptation of the germplasm groups identified to be dominated by reactions to cold temperature and late‐season frost occurrence, as well as to water availability. Several significant associations pointing at specific adaptations to agroclimatic features related to temperature and water availability were observed, and candidate genes underlying some of the main regions are proposed.     

Sexual selection in a hermaphroditic plant through female reproductive success

Sexual selection is well accepted as a mechanism of shaping traits in animals. However, whether and how floral traits are sexually selected in hermaphroditic plants remains less clear. Here, we use Passiflora incarnata to address how floral traits that affect pollination success are selected via female function. We manipulated the ecological context by limiting pollination and adding resources to expand the phenotypic distribution and alter the intensity of sexual selection. Total sexual selection favoured lower style deflexion because of its impact on pollen receipt and subsequent seed number. However, total selection on style deflexion was not significant, indicating additional selection on style deflexion through routes other than mating. Limited pollination and enhanced resources were expected to alter the distribution of pollen deposition and seed production and therefore intensify the Bateman gradient – the relationship between pollen receipt and seed production. Indeed, the Bateman gradient was strongest when pollination was limited, suggesting potential for sexual selection to influence floral trait evolution under these conditions. Overall, we found floral traits may be shaped by sexual selection through female reproductive success in this hermaphroditic plant. These results support manipulations to enhance the variance in mating as a mechanism to understand patterns of sexual selection.     

Fluctuating selection: the perpetual renewal of adaptation in variable environments

Darwin insisted that evolutionary change occurs very slowly over long periods of time, and this gradualist view was accepted by his supporters and incorporated into the infinitesimal model of quantitative genetics developed by R. A. Fisher and others. It dominated the first century of evolutionary biology, but has been challenged in more recent years both by field surveys demonstrating strong selection in natural populations and by quantitative trait loci and genomic studies, indicating that adaptation is often attributable to mutations in a few genes. The prevalence of strong selection seems inconsistent, however, with the high heritability often observed in natural populations, and with the claim that the amount of morphological change in contemporary and fossil lineages is independent of elapsed time. I argue that these discrepancies are resolved by realistic accounts of environmental and evolutionary changes. First, the physical and biotic environment varies on all time-scales, leading to an indefinite increase in environmental variance over time. Secondly, the intensity and direction of natural selection are also likely to fluctuate over time, leading to an indefinite increase in phenotypic variance in any given evolving lineage. Finally, detailed long-term studies of selection in natural populations demonstrate that selection often changes in direction. I conclude that the traditional gradualist scheme of weak selection acting on polygenic variation should be supplemented by the view that adaptation is often based on oligogenic variation exposed to commonplace, strong, fluctuating natural selection.     

Identifying footprints of selection in stocked brown trout populations: a spatio‐temporal approach

Studies of interactions between farmed and wild salmonid fishes have suggested reduced fitness of farmed strains in the wild, but evidence for selection at the genic level is lacking. We studied three brown trout populations in Denmark which have been significantly admixed with stocked hatchery trout (19–64%), along with two hatchery strains used for stocking. The wild populations were represented by contemporary samples (2000–2006) and two of them by historical samples (1943–1956). We analysed 61 microsatellite loci, nine of which showed putative functional relationships [expressed sequence tag (EST)‐linked or quantitative trait loci]. F_ST‐based outlier tests provided support for diversifying selection at chromosome regions marked by three loci, two anonymous and one EST‐linked. Patterns of differentiation suggested that the loci were candidates for being under diversifying hitch‐hiking selection in hatchery vs. wild environments. Analysis of hatchery strain admixture proportions showed that in one wild population, two of the loci showed significantly lower admixture proportions than the putatively neutral loci, implying contemporary selection against alleles introduced by hatchery strain trout. In the most strongly admixed population, however, there was no evidence for selection, possibly because of immigration by stocked trout overcoming selection against hatchery‐derived alleles or supportive breeding practices allowing hatchery strain trout to escape natural selection. To our knowledge, this is the first study demonstrating footprints of selection in wild salmonid populations subject to spawning intrusion by farmed fish.     

Red and blond Mangalitza pigs display a signature of divergent directional selection in the SLC45A2 gene

The Mangalitza lard‐type pig breed is well known for its fat appearance and curly hair, and it is mainly distributed in Eastern Europe. Four main lines were created in the nineteenth century by artificial selection: Blond Mangalitza, Black Mangalitza, Swallow‐Belly Mangalitza and Red Mangalitza. The Swallow‐Belly line has a black coat combined with yellow‐blond throat and underbelly. In the current work, we aimed to investigate if the colourations of Mangalitza pigs are genetically determined by one or a few loci whose frequencies have been modified by artificial selection. The results of selection scans, with Hap FLK and BayeScan , and of a GWAS for coat colour highlighted the existence of one region on SSC16 (18–20 Mb) with potential effects on hair pigmentation (Red vs. Blond contrast). The analysis of the gene content of this region allowed us to detect the solute carrier family 45 member 2 (SLC45A2) locus as a candidate gene for this trait. The polymorphism of the SLC45A2 locus has been associated with reduced levels or the absence of melanin in several mammalian species. The genotyping of four missense polymorphisms evidenced that rs341599992:G > A and rs693695020:G > A SNPs are strongly but not fully associated with the red and blond coat colours of Mangalitza pigs, a result that was confirmed by performing a haplotype association test. The near fixation of alternative SLC45A2 genotypes in Red and Blond Mangalitza pigs provides a compelling example of the consequences of a divergent directional selection for coat colour in a domestic species.     

Origin of the fittest: link between emergent variation and evolutionary change as a critical question in evolutionary biology

In complex organisms, neutral evolution of genomic architecture, associated compensatory interactions in protein networks and emergent developmental processes can delineate the directions of evolutionary change, including the opportunity for natural selection. These effects are reflected in the evolution of developmental programmes that link genomic architecture with a corresponding functioning phenotype. Two recent findings call for closer examination of the rules by which these links are constructed. First is the realization that high dimensionality of genotypes and emergent properties of autonomous developmental processes (such as capacity for self-organization) result in the vast areas of fitness neutrality at both the phenotypic and genetic levels. Second is the ubiquity of context- and taxa-specific regulation of deeply conserved gene networks, such that exceptional phenotypic diversification coexists with remarkably conserved generative processes. Establishing the causal reciprocal links between ongoing neutral expansion of genomic architecture, emergent features of organisms' functionality, and often precisely adaptive phenotypic diversification therefore becomes an important goal of evolutionary biology and is the latest reincarnation of the search for a framework that links development, functioning and evolution of phenotypes. Here I examine, in the light of recent empirical advances, two evolutionary concepts that are central to this framework-natural selection and inheritance-the general rules by which they become associated with emergent developmental and homeostatic processes and the role that they play in descent with modification.     

Past distribution of epiphyllous liverworts in China: The usability of historical data

Epiphyllous liverworts form a special group of bryophytes that primarily grow on the leaves of understory vascular plants in tropical and subtropical evergreen broadleaf forests. Being sensitive to moisture and temperature changes, epiphyllous liverworts are often considered to be good indicators of climate change and forest degradation. However, they are a poorly collected and taxonomically complicated group, with an only partly identified distribution pattern. In this study, we built four models based on 24 environmental variables at four different spatial resolutions (i.e., 1 km, 5 km, 10 km, and 15 km) to predict the past distribution of epiphyllous liverworts in China, using Maxent model and 63 historical location records (i.e., presence‐only data). Both area under the curve of the receiver operating characteristic (AUC) and true skill statistic (TSS) methods are used to assess the model performance. Results showed that the model with the predictors at a 15‐km resolution achieved the highest predictive accuracy (AUC=0.946; TSS=0.880), although there was no statistically significant difference between the four models (p > 0.05). The most significant environmental variables included aridity, annual precipitation, precipitation of wettest month, precipitation of wettest quarter, and precipitation of warmest quarter, annual mean NDVI, and minimum NDVI. The predicted suitable areas for epiphyllous liverworts were mainly located in the south of Yangtze River and seldom exceed 35°N, which were consistent with the museum and herbarium records, as well as the historical records in scientific literatures. Our study further demonstrated the value of historical data to ecological and evolutionary studies.     

kakusan: a computer program to automate the selection of a nucleotide substitution model and the configuration of a mixed model on multilocus data

The application of different substitution models to each gene (a.k.a. mixed model) should be considered in model‐based phylogenetic analysis of multigene sequences. However, a single molecular evolution model is still usually applied. There are no computer programs able to conduct model selection for multiple loci at the same time, though several recently developed types of software for phylogenetic inference can handle mixed model. Here, I have developed computer software named ‘kakusan’ that enables us to solve the above problems. Major running steps are briefly described, and an analysis of results with kakusan is compared to that obtained with other program.     

Evolution of sexual dichromatism in relation to nesting habits in European passerines: a test of Wallace's hypothesis

Wallace proposed in 1868 that natural rather than sexual selection could explain the striking differences in avian plumage dichromatism. Thus, he predicted that nesting habits, through their association with nest predation, could drive changes in sexual dichromatism by enabling females in cavity nesters to become as conspicuous as males, whereas Darwin (1871, The Descent of Man and Selection in Relation to Sex, John Murray, London) argued that sexual selection was the sole explanation for dichromatism. Sexual dichromatism is currently used as indicating the strength of sexual selection, and therefore testing Wallace's claim with modern phylogentically controlled methodologies is of prime interest for comparing the roles of natural and sexual selection in affecting the evolution of avian coloration. Here, we have related information on nest attendance, sexual dichromatism and nesting habits (open and cavity nesting) to male and female plumage conspicuousness in European passerines. Nest incubation attendance does not explain male or female plumage conspicuousness but nest type does. Moreover, although females of monochromatic and cavity nesting species are more conspicuous than females of other species, males of monochromatic and open nesting species are those with more cryptic plumage. Finally, analyses of character evolution suggest that changes in nesting habits influence the probability of changes in both dichromatism and plumage conspicuousness of males but do not significantly affect those in females. These results strongly suggest a role of nesting habits in the evolution of plumage conspicuousness of males, and a role for sexual selection also in females, both factors affecting the evolution of sexual dichromatism. We discuss our findings in relation to the debate that Darwin and Wallace maintained more than one century ago on the importance of natural and sexual selection in driving the evolution of plumage conspicuousness and sexual dichromatism in birds, and conclude that our results partly support the evolutionary scenarios envisaged by both extraordinary scientists.