Research Reveals Sheep Tissue-Specific Gene Regulation

Washington State University

PULLMAN, Wash. — Livestock breeders could soon have more tools to improve the health and quality of their animals, thanks to a recent study that sheds new light on regulatory elements in the sheep genome.

Previous research demonstrated that several areas of the genome, regardless of species, are responsible for modulating or regulating gene expression. This study, the first of its kind on sheep, resulted in a detailed map that illuminates more specifically where those gene promoters and enhancers are located. The findings could help livestock breeders select for beneficial traits such as efficient food digestion or muscle development, while avoiding traits associated with disease.

"A gene promotor is similar to turning a light switch on or off, while an enhancer is akin to a dimmer switch," said study co-author Kimberly Davenport, an assistant professor in Washington State University's Department of Animal Sciences . "The study gives us a clearer picture of what's happening when we're selecting for one trait over another, both genetically and epigenetically. It shows how we can best utilize genetic information to boost the return on investment for producers who use genetics to guide their animal breeding."

In addition to WSU researchers, the paper involved scientists from the University of Idaho, the University of Edinburgh, AgResearch, USDA, GENUS, Baylor University, Utah State University, and the University of Missouri. The findings were published in the journal Nature Communications .

"This is one of the biggest and most ambitious livestock experiments relating to gene regulation," said study co-author Gordon Murdoch, chair of WSU's animal sciences department. "It offers a platform to explore future research across many animal species, and it immediately translates a complex understanding of genetics, making it relevant to the producer."

All living organisms have a genome — essentially a recipe book dictating their unique traits and characteristics, as well as their health and development. In this study, the scientists investigated how gene regulation influences different cell types in sheep and ensures those cells remain true to their function.

"We need to characterize gene regulatory regions in genomes for each species so we can understand the mechanisms that affect gene expression," said study corresponding author Brenda Murdoch, a professor in the University of Idaho's Department of Animal, Veterinary, and Food Sciences . "In general, genes function similarly between species, but mutations within gene regulatory regions and genes are species-specific. We already knew the location of DNA coding genes in the sheep genome, but this study allowed us to discover where in the genome the modulation or regulation of gene expression is taking place."

The findings helped the researchers better understand how changes in the genome affect biological outcomes. It also confirmed that gene regulation controls an organism's phenotype, or observable traits, contributing to what makes each species unique.

Working with samples from the Rambouillet ewe that was previously used to establish the sheep reference genome, the researchers identified the regulatory elements in the sheep's core tissues and main organs, including the heart, liver, lungs, intestines, stomach, and regions of the brain.

"We already had some knowledge about these tissues and their different functions," said Gordon Murdoch. "For example, we knew that brain tissue develops very differently from muscle tissue. Because this experiment validated our previous genetic analysis, we knew we could likely trust anything novel that came out of this study."

The researchers conducted several experiments to explore how DNA attributes help promote or enhance gene expression in the sheep's tissues.

"We are on the cusp of understanding the intricacies of how genotype results in phenotype," said Gordon Murdoch. "When considering ways to improve an animal through breeding, you would never select for traits that are beneficial to one type of tissue but damage another. Tissue differences are critical to animal health, well-being, and functioning. The more we understand about how genes are regulated, the more we can limit undesirable effects in breeding."

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