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First results from ruminant genome project will inform agriculture, conservation and biomedicine

June 20, 2019

A trio of Reports and a Perspective in this issue present the Ruminant Genome Project's (RGP) initial findings, which range from explaining how deer antlers exploit cancer-associated signaling pathways to regenerate, to informing reindeer genetic adaptations - including as relates to circadian rhythm - that have helped these animals thrive in the frigid Arctic. The work provides an unprecedented look into the genomics, evolution and adaptation of ruminants, a group of highly successful and diverse mammals with significant agricultural, conservational and biomedical importance, and one that includes many well-known domestic and wild taxa, such as cows, goats, reindeer and giraffes. Despite the fact that ruminant taxa can be found in most places on the planet, the evolutionary origin and diversification of ruminants as well as the genetics underlying their unique traits remain relatively unknown. To better resolve ruminant genetics, Lei Chen and colleagues assembled the genomes of 44 ruminant species across all six Ruminantia families - a dataset encompassing more than 40 trillion base pairs. Chen et al. then used these, as well as other ruminant genomes, to create a time-calibrated phylogenetic tree of the group, which was able to resolve the evolutionary history of many ruminant genera. Interestingly, the results revealed large declines in ruminant populations nearly 100,000 years ago, reductions that coincide with the migration of humans out of Africa and may be evidence of early humans' impact on various ruminant species, the authors say. In another Report, Yu Wang and colleagues examine the underlying genetics and evolution of ruminant headgear. Ruminants are the only living group of mammals that possess bony headgear, but despite their common composition and cranial location, their form and function is varied among several families. Antlers, like those carried by deer, are capable of rapid growth - as much as 2.5 centimeters a day - and have become a particular interest in regenerative biology. By comparing 221 transcriptomes from headgear-bearing ruminant families and the genomes of two lineages that convergently lack headgear against the genomic background provided by the RGP, Wang et al. found that the horns of bovids and the antlers of cervids share similar genetic and cellular roots. Most striking, however, is the discovery that the regenerative properties of antler tissue are made possible through the unique exploitation of cancer-associated signaling pathways and the high expression of tumor suppressing genes. Intriguingly, the genes and regulatory sequences expressed in these animals allow for tissue regeneration without cancer growth. Reindeer harbor a variety of biological adaptations that allow them to thrive in Arctic environments and survive harsh conditions such as extreme cold, limited food availability and prolonged periods of light and dark. What's more, reindeer are the only fully domesticated cervid species. However, the underlying genetic basis of their unique traits remains largely unknown. Here, Lin et al. closely evaluate the animal's genome and discover that several genes related to circadian arrhythmicity, vitamin D metabolism, docility and female antler growth, are either uniquely mutated and/or under positive selection in reindeer. While the results provide a genetic basis for reindeer Arctic adaptation and domestication, they may also provide insights relevant to human health, suggest the authors. For example, the newly identified genes related to circadian arrhythmicity could inform approaches to treat seasonal affective disorders, insomnia and depression. Finally, in a Perspective, Dai Fei Elmer Ker and Yunzhi Peter Yang discuss their potential implications of the three RGP Reports on future biomedical efforts.
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American Association for the Advancement of Science

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