Runs of homozygosity in Sable Island feral horses reveal the genomic consequences of inbreeding and divergence from domestic breeds

Abstract Background Understanding inbreeding and its impact on fitness and evolutionary potential is fundamental to species conservation and agriculture. Long stretches of homozygous genotypes, known as runs of homozygosity (ROH), result from inbreeding and their number and length can provide useful population-level information on inbreeding characteristics and locations of signatures of selection. However, the utility of ROH for conservation is limited for natural populations where baseline data and genomic tools are lacking. Comparing ROH metrics in recently feral vs. domestic populations of well understood species like the horse could provide information on the genetic health of those populations and offer insight into how such metrics compare between managed and unmanaged populations. Here we characterized ROH, inbreeding coefficients, and ROH islands in a feral horse population from Sable Island, Canada, using ~41 000 SNPs and contrasted results with those from 33 domestic breeds to assess the impacts of isolation on ROH abundance, length, distribution, and ROH islands. Results ROH number, length, and ROH-based inbreeding coefficients (FROH) in Sable Island horses were generally greater than in domestic breeds. Short runs, which typically coalesce many generations prior, were more abundant than long runs in all populations, but run length distributions indicated more recent population bottlenecks in Sable Island horses. Nine ROH islands were detected in Sable Island horses, exhibiting very little overlap with those found in domestic breeds. Gene ontology (GO) enrichment analysis for Sable Island ROH islands revealed enrichment for genes associated with 3 clusters of biological pathways largely associated with metabolism and immune function. Conclusions This study indicates that Sable Island horses tend to be more inbred than their domestic counterparts and that most of this inbreeding is due to historical bottlenecks and founder effects rather than recent mating between close relatives. Unique ROH islands in the Sable Island population suggest adaptation to local selective pressures and/or strong genetic drift and highlight the value of this population as a reservoir of equine genetic variation. This research illustrates how ROH analyses can be applied to gain insights into the population history, genetic health, and divergence of wild or feral populations of conservation concern

Data from: The purging of deleterious mutations in simple and complex mating environments

There is a general expectation that sexual selection should align with natural selection to aid the purging of deleterious mutations, yet experiments comparing purging under monogamy vs. polygamy have provided mixed results. Recent studies suggest that this may be because the simplified mating environments used in these studies reduces the benefit of sexual selection through males and hampers natural selection through females by increasing costs associated with sexual conflict. To test the effect of the physical mating environment on purging, we use experimental evolution in Drosophila melanogaster to track the frequency of four separate deleterious mutations in replicate populations that experience polygamy under either a simple or structurally complex mating arena while controlling for arena size. Consistent with past results suggesting a greater net benefit of polygamy in a complex environment, two of the mutations were purged significantly faster in this environment. The other two mutations showed no significant difference between environments

Mutant allele and homozygote mutant genotype frequencies from experimental populations

This file contains data on mutant allele frequencies and homozygote mutant genotype frequencies at various time points (generations) in independent, replicate populations experimentally evolving in either a complex or simple mating environment. Each row corresponds to a frequency estimate from a particular population in a given generation. Columns are: mutant: the mutation in question; population: an arbitrary ID number given to each replicate population (6 populations per mutation, 3 in each treatment); treatment: simple vs. complex mating treatment; generation: the generation in which the given frequency was estimated; type: whether the frequency is that of the mutant allele (as estimate from a set of test crosses) or the mutant homozygote genotype; frequency - the frequency estimate expressed as a proportion

Table S1. Initial geneotype and allele frequencies. from The purging of deleterious mutations in simple and complex mating environments

Initial genotype and allele frequencies in replicate experimental populations of each mutation upon their foundin

Figure S1. Pictures of the simple complex mating arenas. from The purging of deleterious mutations in simple and complex mating environments

Overhead views of the simple and complex mating arenas with the lids removed and inverted

A genome-wide gain-of-function screen identifies CDKN2C as a HBV host factor

International audienceChronic HBV infection is a major cause of liver disease and cancer worldwide. Approaches for cure are lacking, and the knowledge of virus-host interactions is still limited. Here, we perform a genome-wide gain-of-function screen using a poorly permissive hepatoma cell line to uncover host factors enhancing HBV infection. Validation studies in primary human hepatocytes identified CDKN2C as an important host factor for HBV replication. CDKN2C is overexpressed in highly permissive cells and HBV-infected patients. Mechanistic studies show a role for CDKN2C in inducing cell cycle G1 arrest through inhibition of CDK4/6 associated with the upregulation of HBV transcription enhancers. A correlation between CDKN2C expression and disease progression in HBV-infected patients suggests a role in HBV-induced liver disease. Taken together, we identify a previously undiscovered clinically relevant HBV host factor, allowing the development of improved infectious model systems for drug discovery and the study of the HBV life cycle