Regions of Homozygosity in the Porcine Genome: Consequence of Demography and the Recombination Landscape

Abstract

Inbreeding has long been recognized as a primary cause of fitness reduction in both wild and domesticated populations. Consanguineous matings cause inheritance of haplotypes that are identical by descent (IBD) and result in homozygous stretches along the genome of the offspring. Size and position of regions of homozygosity (ROHs) are expected to correlate with genomic features such as GC content and recombination rate, but also direction of selection. Thus, ROHs should be non-randomly distributed across the genome. Therefore, demographic history may not fully predict the effects of inbreeding. The porcine genome has a relatively heterogeneous distribution of recombination rate, making Sus scrofa an excellent model to study the influence of both recombination landscape and demography on genomic variation. This study utilizes next-generation sequencing data for the analysis of genomic ROH patterns, using a comparative sliding window approach. We present an in-depth study of genomic variation based on three different parameters: nucleotide diversity outside ROHs, the number of ROHs in the genome, and the average ROH size. We identified an abundance of ROHs in all genomes of multiple pigs from commercial breeds and wild populations from Eurasia. Size and number of ROHs are in agreement with known demography of the populations, with population bottlenecks highly increasing ROH occurrence. Nucleotide diversity outside ROHs is high in populations derived from a large ancient population, regardless of current population size. In addition, we show an unequal genomic ROH distribution, with strong correlations of ROH size and abundance with recombination rate and GC content. Global gene content does not correlate with ROH frequency, but some ROH hotspots do contain positive selected genes in commercial lines and wild populations. This study highlights the importance of the influence of demography and recombination on homozygosity in the genome to understand the effects of inbreeding.

Mining the pig genome to investigate the domestication process

“…Phylogenomic analyses estimated a split between Asian and European lineages at 0.8-1.6 MYA, a result supported by the considerable number of fixed differences between these groups and consistent with previous studies (for example, Megens et al, 2008). These differences in population sizes are reflected on the estimates of nucleotide diversity (p) calculated at the whole-genome level (Bosse et al, 2012), suggesting that wild boars from Asia are the most diverse specimens (p B0.0030 variants per base pair). In contrast, European wild boars (p B0.0010) would be the least diverse population.…”

“…In addition, historical admixture with wild boars may have also had a role until a few hundred years ago (White, 2011;Goedbloed et al, 2013;Manunza et al, 2013). Amaral et al (2011) observed a positive correlation between the level of variability and recombination (also observed in Badke et al, 2012;Bosse et al, 2012 andEsteve-Codina et al, 2013), suggesting that selection (positive or negative) has an active role in shaping the variability of Sus scrofa and that interference among genomic positions has an impact on variability. The significant presence of candidate mutations that are functionally harmful suggests that many of the variants that have been artificially selected were new variants with strong effects (as indicated in Rubin et al, 2012).…”

“…Nevertheless, this general reduction of variability is not observed in domesticated European populations. In fact, variability is higher in European domestic pigs (Bosse et al, 2012) mainly due to the intense admixture with Asian pigs and the selection of advantageous Asian mutations that has occurred in these lineages (Ojeda et al, 2011). In addition, historical admixture with wild boars may have also had a role until a few hundred years ago (White, 2011;Goedbloed et al, 2013;Manunza et al, 2013).…”

Comprehensive variation discovery and recovery of missing sequence in the pig genome using multiple de novo assemblies

“…As with the SNPs, distribution of indels across the genome also reflected a deep phylogenetic split between European and Chinese pigs and higher genetic variability of Chinese pigs than European pigs (Supplemental Fig. S22; Bosse et al 2012;Groenen et al 2012). …”

“…S13B; White 2011). Another possible explanation is that European wild boars (ancestors of European domestic pigs) may have suffered more pronounced population bottlenecks during the last glacial maximum (∼20,000 yr ago) compared to their Asian counterparts (Bosse et al 2012;Groenen et al 2012).…”