Uncovering the architecture of selection in two Bos taurus cattle breeds

Selection alters the genome via hard sweeps, soft sweeps, and polygenic selection. However, mapping polygenic selection is difficult because it does not leave clear signatures on the genome like a selective sweep. In populations with temporally-stratified genotypes, the Generation Proxy Selection Mapping (GPSM) method identifies variants associated with generation number (or appropriate proxy) and thus variants undergoing directional allele frequency changes. Here, we use GPSM on two large datasets of beef cattle to detect associations between an animal's generation and 11 million imputed SNPs. Using these datasets with high power and dense mapping resolution, GPSM detected a total of 294 unique loci actively under selection in two cattle breeds. We observed that GPSM has a high power to detect selection in the very recent past (< 10 years), even when allele frequency changes are small. Variants identified by GPSM reside in genomic regions associated with known breed characteristics, such as fertility and maternal ability in Red Angus and carcass merit and coat color in Simmental. Over 60% of the selected loci reside in or near (<50 kb) annotated genes. Additionally, 36% of selected loci overlap known epigenetic marks or putative functional genomic regions. Using RAiSD and nSL, we identify hundreds of putative selective sweeps; however, these sweeps have little overlap with polygenic selected loci. This makes GPSM a complementary approach to sweep detection methods when temporal genotype data are available. The selected loci that we identify across methods demonstrate the complex architecture of selection in domesticated cattle.

Rapid Evolutionary Adaptation in Response to Selection on Quantitative Traits

Evolutionary adaptation after sudden environmental changes can occur very rapidly. The mechanisms facilitating rapid adaptation range from strong positive directional selection leading to large shifts in the allele frequencies at a few loci (selective sweeps) to polygenic selection causing small changes in allele frequencies at many loci. In addition, combinations of these two extreme mechanisms may also result in fast evolution. In recent years, following reports of new case studies of rapid adaptation, population genetic models have been proposed to explain these observations. In these models, the role of the major selective forces (positive directional and stabilizing selection) is highlighted as well as the genetic architecture of quantitative traits. Furthermore, the factors limiting the speed of adaptation are analyzed, in particular, the effects of random genetic drift and demography due to finite population size.

Powerful detection of polygenic selection and evidence of environmental adaptation in US beef cattle

Selection on complex traits can rapidly drive evolution, especially in stressful environments. This polygenic selection does not leave intense sweep signatures on the genome, rather many loci experience small allele frequency shifts, resulting in large cumulative phenotypic changes. Directional selection and local adaptation are changing populations; but, identifying loci underlying polygenic or environmental selection has been difficult. We use genomic data on tens of thousands of cattle from three populations, distributed over time and landscapes, in linear mixed models with novel dependent variables to map signatures of selection on complex traits and local adaptation. We identify 207 genomic loci associated with an animal’s birth date, representing ongoing selection for monogenic and polygenic traits. Additionally, hundreds of additional loci are associated with continuous and discrete environments, providing evidence for historical local adaptation. These candidate loci highlight the nervous system’s possible role in local adaptation. While advanced technologies have increased the rate of directional selection in cattle, it has likely been at the expense of historically generated local adaptation, which is especially problematic in changing climates. When applied to large, diverse cattle datasets, these selection mapping methods provide an insight into how selection on complex traits continually shapes the genome. Further, understanding the genomic loci implicated in adaptation may help us breed more adapted and efficient cattle, and begin to understand the basis for mammalian adaptation, especially in changing climates. These selection mapping approaches help clarify selective forces and loci in evolutionary, model, and agricultural contexts.

Polygenic selection within a single generation leads to subtle divergence among ecological niches

Selection on standing genetic variation may be effective enough to allow for adaptation to distinct niche environments within a single generation. Minor allele frequency changes at multiple, redundant loci of small effect can produce remarkable phenotypic shifts. Yet, demonstrating rapid adaptation via polygenic selection in the wild remains challenging. Here we harness natural replicate populations that experience similar selection pressures and harbor high within-, yet negligible among-population genetic variation. Such populations can be found among the teleost Fundulus heteroclitus which inhabits marine estuaries characterized by high environmental heterogeneity. We identify 10,861 single nucleotide polymorphisms in F. heteroclitus that belong to a single, panmictic population yet reside in environmentally distinct niches (one coastal basin and three replicate tidal ponds). By sampling at two time-points within a single generation we quantify both allele frequency change within as well as spatial divergence among niche subpopulations. We observe few individually significant allele frequency changes yet find that the number of moderate changes exceeds the neutral expectation by 10-100%. We find allele frequency changes to be significantly concordant in both direction and magnitude among all niche subpopulations, suggestive of parallel selection. In addition, within-generation allele frequency changes generate subtle but significant divergence among niches, indicative of local adaptation. Although we cannot distinguish between selection and genotype-dependent migration as drivers of within-generation allele frequency changes, the trait/s determining fitness and/or migration likelihood appear to be polygenic. In heterogeneous environments, polygenic selection and polygenic, genotype-dependent migration offer conceivable mechanisms for within-generation, local adaptation to distinct niches.

Leveraging large scale beef cattle genomic data to identify the architecture of polygenic selection and local adaptation

Since the invention of the first array-based genotyping assay for cattle in 2008, millions of animals have been genotyped worldwide. Leveraging these genotypes offers exciting opportunities to explore both basic and applied research questions. Commercial genotyping assays are of adequate variant density to perform well in prediction contexts but are not sufficient for mapping studies. Using reference panels made up of individuals genotyped at higher densities, we can statistically infer the missing variation of low-density assays through the process of imputation. Here, we explore the best practices for performing routine imputation in large commercially generated genomic datasets of U.S. beef cattle. We find that using a large multi-breed imputation reference maximizes accuracy, particularly for rare variants. Using three of these large, imputed datasets, we explore two major population genetics questions. First, we map polygenic selection in the bovine genome, using Generation Proxy Selection Mapping (GPSM). This identifies hundreds of regions of the genome actively under selection in cattle populations. Using a similar approach, we identify dozens of genomic variants associated with environments across the U.S., likely involved local adaptation. Understanding the genomic basis of local adaptation in cattle will enable select and breed cattle better suited to a changing climate.

The structural variation landscape in 492 Atlantic salmon genomes

Structural variants (SVs) are a major source of genetic and phenotypic variation, but remain challenging to accurately type and are hence poorly characterized in most species. We present an approach for reliable SV discovery in non-model species using whole genome sequencing and report 15,483 high-confidence SVs in 492 Atlantic salmon (Salmo salar L.) sampled from a broad phylogeographic distribution. These SVs recover population genetic structure with high resolution, include an active DNA transposon, widely affect functional features, and overlap more duplicated genes retained from an ancestral salmonid autotetraploidization event than expected. Changes in SV allele frequency between wild and farmed fish indicate polygenic selection on behavioural traits during domestication, targeting brain-expressed synaptic networks linked to neurological disorders in humans. This study offers novel insights into the role of SVs in genome evolution and the genetic architecture of domestication traits, along with resources supporting reliable SV discovery in non-model species.

Genome evolution in an agricultural pest following adoption of transgenic crops

Replacement of synthetic insecticides with transgenic crops for pest management has been both economically and environmentally beneficial. These benefits have often eroded as pests evolved resistance to the transgenic crops, but a broad understanding of the timing and complexity of the adaptive changes which lead to field-evolved resistance in pest species is lacking. Wild populations of Helicoverpa zea, a major lepidopteran crop pest and the target of transgenic Cry toxin-expressing cotton and corn, have recently evolved widespread, damaging levels of resistance. Here, we quantified patterns of genomic change in wild H. zea collected between 2002 and 2017 when adoption rates of Cry-expressing crops expanded in North America. Using a combination of genomic and genotypic approaches, we identified significant temporal changes in allele frequency throughout the genomes of field-collected H. zea. Many of these changes occurred concurrently with increasingly damaging levels of resistance to Cry toxins between 2012 and 2016, in a pattern consistent with polygenic selection. Surprisingly, none of the eleven previously described Cry resistance genes showed signatures of selection in wild H. zea. Furthermore, we observed evidence of a very strong selective sweep in one region of the H. zea genome, yet this strongest change was not additively associated with Cry resistance. This first, whole genome analysis of field-collected specimens to study evolution of Cry resistance demonstrates the potential and need for a more holistic approach to examining pest adaptation to changing agricultural practices.

The structural variation landscape in 492 Atlantic salmon genomes

Structural variants (SVs) are a major source of genetic and phenotypic variation, but remain challenging to accurately type and are hence poorly characterized in most species. We present an approach for reliable SV discovery in non-model species using whole genome sequencing and report 15,483 high-confidence SVs in 492 Atlantic salmon (Salmo salar L.) sampled from a broad phylogeographic distribution. These SVs recover population genetic structure with high resolution, include an active DNA transposon, widely affect functional features, and overlap more duplicated genes retained from an ancestral salmonid autotetraploidization event than expected. Changes in SV allele frequency between wild and farmed fish indicate polygenic selection on behavioural traits during domestication, targeting brain-expressed synaptic networks linked to neurological disorders in humans. This study offers novel insights into the role of SVs in genome evolution and the genetic architecture of domestication traits, along with resources supporting reliable SV discovery in non-model species.

Using singleton densities to detect recent selection in Bos taurus

Many quantitative traits are subject to selection, where several genomic regions undergo small, simultaneous changes in allele frequency that collectively alter a phenotype. The widespread availability of genome data, along with novel statistical techniques, has made it easier to detect these changes. We apply one such method, the ‘Singleton Density Score’, to the Holstein breed of Bos taurus to detect recent selection (arising up to around 740 years ago). We identify several candidate genes for recent selection, including some relating to protein and cell regulation, the synaptic system, body growth, and immunity. We do not find strong evidence that two traits important for humans, milk–protein content and stature, have been subject to directional selection. These results inform on which genes underlie recent domestication in B. taurus. We propose how polygenic selection can be best investigated in future studies.