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

Data Availability Statement: Full-length MYH3 CDS sequence from KNP, KX538787; full-length MYH3 CDS sequence from Landrace, KX538788. Two-kb of 5’-UTR MYH3 genomic DNA sequence from KNP, KX549312; 0.5-kb of 3’-UTR MYH3 genomic DNA sequence from KNP, KX549313. Two-kb of 5’-UTR MYH3 genomic DNA sequence from Landrace, KX549311; 0.5-kb of 3’-UTR MYH3 genomic DNA sequence from Landrace, KX549314. Resequencing data access information is provided in S10 Table. All the raw data to produce figures and tables are available at https://datadryad.org/review?doi=doi:10.5061/dryad.dr32n87
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.
This work was carried out with the support of >Cooperative Research Program for Agriculture Science & Technology Development (Project title: A research on performance improvement of ‘Nanchukmacdon’, a high quality pig breed developed using Korean native black pigs (KNP) in Jeju Island, Project No. PJ01012301 and PJ01262701)> Rural Development Administration (http://www.rda.go.kr), Republic of Korea. This work was also supported by the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program, Republic of Korea (www.kribb.re.kr). M.P.E work was funded by AGL2016-78709-R (Ministerio de Economía y Competitividad, Spain; http://www.mineco.gob.es/portal/site/mineco/). T