A big boost for a new epigenetic paradigm: CoRSIV, first discovered in humans, is now found in cattle

A study published in Genome Biology opens new possibilities for improving production efficiency in the beef industry and potentially in animal agriculture in general. A team of researchers from Baylor College of Medicine, Cornell University and the USDA has discovered that, like humans, cattle carry CoRSIV.

CoRSIVs are regions of the genome carrying chemical markers on DNA that provide information that can help farmers predict and select for desirable traits in livestock, such as milk production, female fertility and disease resistance.

“Most people know that each person has a unique set of genes or genome, but what is less well known is that the expression of these genes is regulated by a system of molecular markings on DNA – epigenetics – that tells different cells in the body which genes to turn on and off,” said co-corresponding author Robert A. Waterland, MD, professor of pediatrics and nutrition at Baylor’s USDA/ARS Child Nutrition Research Center.

“We focus on DNA methylation, that is, the addition of methyl groups, the most stable epigenetic mark. Differences in DNA methylation between individuals can affect their risk of disease.”

In 2019, Waterland and colleagues discovered that the human genome contains special regions called CoRSIV, correlated regions of systemic interindividual variation.

In CoRSIV, DNA methylation levels differ from person to person, but are consistent across different tissues in each individual. This means that CoRSIV methylation can be measured in easily accessible tissues like blood, providing insights into epigenetic regulation in internal organs like the brain, ovaries, or liver.

Their previous work reported nearly 10,000 CoRSIVs in the human genome and suggested that studying these new regions is an effective way to uncover the epigenetic causes of disease. Indeed, CoRSIVs have already been linked to a variety of health problems, including cancer, thyroid function, cognition, type 2 diabetes, cleft palate, schizophrenia, childhood obesity, and autism spectrum disorders.

In the current study, the researchers investigated whether cattle also carried CoRSIV. The team analyzed whole-genome DNA methylation sequencing data from multiple tissues from each of two Holstein cows.

“The algorithm we developed indicates that cattle do indeed carry CoRSIV,” said first author Wen-Jou Chang, a bioinformatics analyst in the Waterland lab. “What’s even more exciting is that we showed that bovine CoRSIV shares major features with those in humans, suggesting that CoRSIV is likely present in other mammals. The race is on to find them in other species, such as horses and pigs.”

“We validated our computational results with laboratory analysis of liver, kidney, brain and blood tissues from 20 different Holstein calves to confirm some of the CoRSIVs identified by Wen-Jou,” said Waterland, a member of Baylor’s Dan L Duncan Comprehensive Cancer Center. “This independent validation greatly strengthened the study.”

Dr Yi Athena Ren, co-author and assistant professor in the Department of Animal Sciences at Cornell University, said: “In recent decades, cattle breeding has focused on genetic selection to achieve substantial progress in dairy production. CoRSIV may offer a new approach to improve selection for desirable traits for the beef industry in a sustainable manner that reduces costs and environmental impacts.”

“Bovine CoRSIV, like those in humans, establishes itself early in life and remains stable throughout the individual’s life,” Waterland said.

“In newborn cattle, methylation profiles in CoRSIV subsets can help predict future performance. They can be associated with specific desirable traits, such as high milk production, high female fertility, disease resistance or even heat tolerance, allowing the selection of individual calves with traits that will lead to increased productivity.”

The researchers showed that, as in humans, the establishment of DNA methylation in bovine CoRSIV is influenced by the early embryo environment.

“This suggests that adjusting embryo culture conditions during assisted reproduction may provide opportunities to tailor agricultural outcomes through epigenetic engineering,” Ren said.

“In addition to aiding in the selection of desirable traits, CoRSIVs can help understand disease processes and individual variation in cattle. And if, as we believe, CoRSIVs are a general feature of the mammalian genome, these agricultural opportunities are not limited to cattle.”