Abstract
BackgroundIn this work, we investigated sequence variation, evolutionary constraint, and selection at the CD163 gene in pigs. A functional CD163 protein is required for infection by porcine reproductive and respiratory syndrome virus, which is a serious pathogen with major impacts on pig production.ResultsWe used targeted pooled sequencing of the exons of CD163 to detect sequence variants in 35,000 pigs of diverse genetic backgrounds and to search for potential stop-gain and frameshift indel variants. Then, we used whole-genome sequence data from three pig lines to calculate: a variant intolerance score that measures the tolerance of genes to protein coding variation; an estimate of selection on protein-coding variation over evolutionary time; and haplotype diversity statistics to detect recent selective sweeps during breeding.ConclusionsUsing a deep survey of sequence variation in the CD163 gene in domestic pigs, we found no potential knockout variants. The CD163 gene was moderately intolerant to variation and showed evidence of positive selection in the pig lineage, but no evidence of recent selective sweeps during breeding.
Highlights
In this work, we investigated sequence variation, evolutionary constraint, and selection at the CD163 gene in pigs
A functional CD163 protein is required for infection by porcine reproductive and respiratory syndrome virus (PRRSV) [1], which is a serious pathogen with major impacts on pig production [2]
PRRSV-resistant genomeedited pigs with a modified CD163 gene have been developed, either by knocking out the gene completely or by targeting its fifth scavenger receptor cysteine-rich (SRCR) domain, which is essential for virus PRRSV infection [3,4,5,6]
Summary
We investigated sequence variation, evolutionary constraint, and selection at the CD163 gene in pigs. A functional CD163 protein is required for infection by porcine reproductive and respiratory syndrome virus, which is a serious pathogen with major impacts on pig production. A functional CD163 protein is required for infection by porcine reproductive and respiratory syndrome virus (PRRSV) [1], which is a serious pathogen with major impacts on pig production [2]. Given that genome editing of CD163 has led to PRRVS-resistant pigs, we wanted to determine if natural knockout variants for the CD163 gene could be identified in elite pigs, in order to investigate the opportunity to select for resistance to PPRSV within existing breeding programs. The aims of this paper were to survey CD163 sequence variation for such naturally occurring knockout variants (i.e., stop-gain and frameshift variants that likely disrupt gene function), and to compare the CD163 sequence variation to genomic distributions of selection and constraint. We used targeted pooled sequencing of CD163 exons to detect sequence variants in 35,000 pigs
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