International Collaboration Completes First-Ever Sheep Genome Sequence

April Flowers for redOrbit.com – Your Universe Online

The first complete sequence of the sheep genome has been completed by an international team of scientists after eight years of collaboration.

The 73 team members from 26 institutions across eight countries included scientists from the Human Genome Sequencing Center at Baylor College of Medicine, CSIRO Australia, BGI Shenzhen in China and the University of Edinburgh, among many others. Their findings, published online in Science, shed new light on the species’ unique and specialized digestive and metabolic systems.

Sheep are very important to the agriculture industry, as they provide a major source of meat, milk and fiber in the form of wool. In Australia alone, there are more than 70 million sheep. Globally, the number reaches close to one billion. Because of such abundance, the results of this study could have a massive impact for the rural economy of many countries.

“We investigated the completed genome to determine which genes are present in a process called gene annotation, which resulted in an advanced understanding of the genes involved in making sheep the unique animals that they are,” said CSIRO project leader Dr Brian Dalrymple.

“Given the importance of wool production, we focused on which genes were likely to be involved in producing wool. We identified a new pathway for the metabolism of lipid in sheep skin, which may play a role in both the development of wool and in the efficient production of wool grease (lanolin).”

The researchers identified a previously unknown gene representing a subfamily of the late cornified envelope (LCE) genes. This gene, called LCE7A, is expressed in the skin of sheep, cattle and goat, but not in the rumen (the first chamber of their stomach which helps digests plant material to animal protein). They also found that LCE7A is expressed under positive selection in sheep. They believe that the expansion of these gene is associated with wool formation.

BGI researchers also examined the MOGAT pathway in sheep skin, assuming it might facilitate wool production. In sheep, they found that MOGAT2 and MOGAT3 had undergone tandem gene expression. Furthermore, they were expressed in the sheep’s skin, not in the liver. In humans, MOGAT3 is an important liver enzyme-encoding gene. This suggests that the loss of MOGAT2 and MOGAT3 in the sheep liver may reduce the importance of the liver in metabolizing long chain fatty acids in ruminants when compared to non-ruminants.

The team, called the International Sheep Genomics Consortium, revealed another key finding involving the rumen, which is essential for the animals to convert hard-to-digest plant materials into animal protein. The rumen, thought to have evolved around 35-40 million years ago, has a tough, keratin-rich surface that is similar to skin. The researchers identified many genes normally expressed in the skin that were also highly expressed in the rumen, as well as a number of new genes that are rumen-specific. Among this latter group, one gene appears to be present in most mammals, but so far has only been identified as being expressed in ruminants.

For the study, the research group assembled the reference genome from two Texel sheep. They conducted RNA-Seq on 94 tissue samples collected from 40 tissues, including 83 from additional Texel sheep. The reference genome is approximately 2.61Gb, with ~99 percent anchored onto the 26 autosomes and the X chromosome. Many segmental duplications were found in the sheep genome. The team identified 4,850 single-copy orthologous genes when they compared the sheep genome to the sequences of goat, cattle, yak, pig, camel, horse, dog, mouse, opossum and human proteins. From these genes, they constructed a phylogenetic tree.

The study is the first to pinpoint the unique genetic qualities that differentiate sheep from other animals, and may someday lead to the development of DNA testing to speed-up selective breeding programs to improve stock. The results might also reveal new insights into diseases that affect sheep.

According to Professor Alan Archibald, Head of Genetics and Genomics at The Roslin Institute, “Sheep were one of the first animals to be domesticated for farming and are still an important part of the global agricultural economy. Understanding more about their genetic make-up will help us to breed healthier and more productive flocks.”

Sheep are also an important biomedical model, and the genetic sequence provided by the research team will help to build a strong foundation or the detailed exploration of the similarities and differences between sheep and humans at the molecular level. The research team hopes that this will lead to improved medical therapies for a number of conditions such as sepsis and asthma.