Journal Article

A functional regulatory variant of MYH3 influences muscle fiber-type composition and intramuscular fat content in pigs

Han, Sang-Hyun, Yoo, Chae-Kyoung, Pérez-Enciso, Miguel, Lee, Jun-Heon, Cho, In-Cheol, Park, Hee-Bok, Kang, Yong-Jun, Jung, Eun-Ji, Lee, Sung-Soo, Ko, Moon-Suck, Andersson, Göran, Kim, Dong-Hwan, Lim, Hyun-Tae, Ahn, Jin Seop, Kim, Sang-Geum, Ryu, Youn-Chul, Hwang, Seongsoo, Shin, Hyun-Sook, Lee, Jae-Bong, Park, Beom-Young, Sun, Wu-Sheng, Kim, Yoo-Kyung, Lee, Kichoon, Lee, Jeong-Woong, Seong, Pil-Nam, Ramayo-Caldas, Yuliaxis, Hwang, In-Sul

2019

Overview

Muscle development and lipid accumulation in muscle critically affect meat quality of livestock. However, the genetic factors underlying myofiber-type specification and intramuscular fat (IMF) accumulation remain to be elucidated. Using two independent intercrosses between Western commercial breeds and Korean native pigs (KNPs) and a joint linkage-linkage disequilibrium analysis, we identified a 488.1-kb region on porcine chromosome 12 that affects both reddish meat color (a*) and IMF. In this critical region, only the MYH3 gene, encoding myosin heavy chain 3, was found to be preferentially overexpressed in the skeletal muscle of KNPs. Subsequently, MYH3-transgenic mice demonstrated that this gene controls both myofiber-type specification and adipogenesis in skeletal muscle. We discovered a structural variant in the promotor/regulatory region of MYH3 for which Q allele carriers exhibited significantly higher values of a* and IMF than q allele carriers. Furthermore, chromatin immunoprecipitation and cotransfection assays showed that the structural variant in the 5'-flanking region of MYH3 abrogated the binding of the myogenic regulatory factors (MYF5, MYOD, MYOG, and MRF4). The allele distribution of MYH3 among pig populations worldwide indicated that the MYH3 Q allele is of Asian origin and likely predates domestication. In conclusion, we identified a functional regulatory sequence variant in porcine MYH3 that provides novel insights into the genetic basis of the regulation of myofiber type ratios and associated changes in IMF in pigs. The MYH3 variant can play an important role in improving pork quality in current breeding programs.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adipogenesis / Adipogenesis - genetics / Adipose Tissue - growth & development / Adipose Tissue - metabolism / Agriculture / Alleles / Animal biology / Animal sciences / Animals / Bioinformatics / Biology and Life Sciences / Biotechnology / Breeding / Breeding of animals / Chromatin / Chromosome 12 / Cytoskeletal Proteins - genetics / Domestication / Flanking region / Funding / Gene expression / Gene Expression Regulation / Genes / Genetic engineering / Genetic factors / Genetics / Genome-Wide Association Study / Genomes / Genomics / Genotype / Hogs / Immunoprecipitation / Life Sciences / Linkage analysis / Linkage disequilibrium / Livestock / Meat / Medicine and Health Sciences / Mice / Mice, Transgenic / Muscle Fibers, Skeletal - metabolism / Muscle proteins / Muscle, Skeletal - growth & development / Muscle, Skeletal - metabolism / MyoD protein / Myogenesis / Myosin / Myosin Heavy Chains - genetics / Myosins - genetics / National parks / Novels / Nucleotide Motifs / Population genetics / Pork / Regulatory sequences / Research and Analysis Methods / Rural development / Skeletal muscle / Software / Sus scrofa - genetics / Sus scrofa - metabolism / Swine / Transgenic mice / Zoology