Abstract
Simple SummaryDomestication and the subsequent selection of animals for either economic or morphological features can impact the legacy genome of a population in myriad ways. In sheep, the rs426272889 single nucleotide polymorphism (SNP) was identified as the peak of a signature of selection. We examined phenotypic data and identified associations for the Transmembrane protein 8B (TMEM8B) rs426272889 SNP and its genetically linked Sperm-associated antigen 8 (SPAG8) rs160159557 SNP with ewe mature weight in four sheep breeds. These data provided the first production-relevant phenotypes, as well as the first organism-level (as opposed to cellular or tumor-derived) phenotypes, associated with TMEM8B, and in so doing, improved the annotation of this gene and genomic region by adding body weight implications. Once validated, these data can be applied in genetic or genomic selection aiming to achieve desired mature body weight.Signature of selection studies have identified many genomic regions with known functional importance and some without verified functional roles. Multiple studies have identified Transmembrane protein 8B (TMEM8B) rs426272889 as having been recently under extreme selection pressure in domesticated sheep, but no study has provided sheep phenotypic data clarifying a reason for extreme selection. We tested rs426272889 for production trait association in 770 U.S. Rambouillet, Targhee, Polypay, and Suffolk sheep. TMEM8B rs426272889 was associated with mature weight at 3 and 4 years (p < 0.05). This suggested selection for sheep growth and body size might explain the historical extreme selection pressure in this genomic region. We also tested Sperm-associated antigen 8 (SPAG8) rs160159557 encoding a G493C substitution. While this variant was associated with mature weights at ages 3 and 4, it was not as strongly associated as TMEM8B rs426272889. Transmembrane protein 8B has little functional information except as an inhibitor of cancer cell proliferation. To our knowledge, this is the first study linking TMEM8B to whole organism growth and body size under standard conditions. Additional work will be necessary to identify the underlying functional variant(s). Once identified, such variants could be used to improve sheep production through selective breeding.
Highlights
Sheep were domesticated in the Fertile Crescent, where their wild relatives remain, 10,500 years before the present [1]
While Polypay, Rambouillet, and Targhee sheep breeds were found polymorphic for Transmembrane protein 8B (TMEM8B) rs426272889 and Sperm-associated antigen 8 (SPAG8) rs160159557 SNPs, the Suffolk breed was monomorphic for these loci (Tables S3 and S4), so they were not used for further analysis
Similar associations were observed in Rambouillet single-breed analysis (Tables S5 and S6), except for spring weight at 3 years of age, which showed a trend toward significance for TMEM8B rs426272889 (p = 0.058) and for SPAG8 rs160159557 (p = 0.087)
Summary
Sheep were domesticated in the Fertile Crescent, where their wild relatives remain, 10,500 years before the present [1]. Domestication and artificial selection triggered positive selection for many traits in domestic species, reshaped livestock genomes, and left “footprints” called selection signatures [2]. These footprints can be used to identify genetic loci subjected to selection in the recent evolutionary past, including many involved with important livestock traits. The identification of such loci under selection may help to understand the molecular mechanisms involved in adaptation and may be useful in identifying regions associated with important traits that are under selection [3]. Kijas et al [2] suggested Natriuretic peptide receptor-B (NPR2) as the nearest candidate gene based on genome annotation at the time, the SNP is located in the intron of Transmembrane protein 8B (TMEM8B) according to a more recent sheep genome assembly
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