The selected genes NR6A1, RSAD2-CMPK2, and COL3A1 contribute to body size variation in Meishan pigs through different patterns

J Anim Sci. 2023 Jan 3:101:skad304. doi: 10.1093/jas/skad304.

Abstract

The high-fertility Meishan pig is currently categorized into medium sized (MMS) and small sized (SMS) based on body size. To identify causal genes responsible for the variation in body size within the two categories, we sequenced individuals representing the entire consanguinity of the existing Meishan pig. This enabled us to conduct genome selective signal analysis. Our findings revealed the genomes of MMS and SMS are stratified, with selective sweep regions formed by differential genomic intervals between the two categories enriched in multiple pig body size related quantitative trait loci (QTLs). Furthermore, the missense mutation c.575T > C of candidate causal gene NR6A1, accounting for the variation in lumbar vertebrae number in pigs, was positively selected in MMS only, leading to an increase in body length of MMS at 6 months of age. To precisely identify causal genes accounting for body size variation through multi-omics, we collected femoral cartilage and liver transcription data from MMS and SMS respectively, and re-sequencing data from pig breeds exhibiting varying body sizes. We found that two selected regions where the RSAD2-CMPK2 and COL3A1 genes are located, respectively, showed different haplotypes in pig breeds of varying body size, and was associated with body or carcass length in hybridized Suhuai pig. Additionally, the above three hub genes, were significantly greater expressed in SMS femoral cartilage and liver tissues compared to MMS. These three genes could strengthen the pathways related to bone resorption and metabolism in SMS, potentially hindering bone and skeletal development and resulting in a smaller body size in SMS. These findings provide valuable insights into the genetic mechanism of body size variation in Meishan pig population.

Keywords: COL3A1; NR6A1; RSAD2-CMPK2; Meishan pig; body size; bone resorption and digestion.

Plain language summary

The existing well-known Meishan pig population has been categorized into medium sized (MMS), and small sized (SMS) based on body size, which is a result of artificial selection. MMS is relatively large in all body size traits, but otherwise have highly similar appearance and performance traits. To effectively identify the candidate selected genes that contribute to the body size variation in Meishan pigs, this study collected individuals from all lineages of MMS and SMS for re-sequencing. Additionally, femoral cartilage and liver transcription data were collected from MMS and SMS, respectively, and re-sequencing data from pig breeds exhibiting varying body sizes were also analyzed. Through multi-omics analysis, it was discovered that the missense mutation c.575T > C in the candidate causal gene NR6A1 was positively selected in MMS only, leading to an increase in the body length of MMS at 6 months of age. Moreover, the selected genes RSAD2-CMPK2 and COL3A1 were found to be significantly greater expressed in SMS femoral cartilage and liver tissues compared with MMS. These genes could potentially strengthen bone resorption and metabolism-related pathways in SMS. These findings contribute to a better understanding of the genetic mechanisms underlying body size variation in Meishan pigs and Chinese indigenous pigs.

MeSH terms

  • Animals
  • Base Sequence
  • Body Size / genetics
  • Collagen Type III* / genetics
  • Haplotypes
  • Nuclear Receptor Subfamily 6, Group A, Member 1* / genetics
  • Nucleoside-Phosphate Kinase* / genetics
  • Oxidoreductases Acting on CH-CH Group Donors*
  • Quantitative Trait Loci*
  • Sus scrofa
  • Swine / genetics
  • Viperin Protein* / genetics

Substances

  • Collagen Type III
  • Nuclear Receptor Subfamily 6, Group A, Member 1
  • Oxidoreductases Acting on CH-CH Group Donors
  • RSAD2 protein, human
  • Viperin Protein
  • Nucleoside-Phosphate Kinase