Cow genome sequence opens the door to a new era of breeding.
A white-faced, red-coated Hereford cow named Dominette has become the first cow to have its genome sequenced.
Information from the 5-year, US$53-million cow-genome project is being used to trace the genetic legacy of bovine domestication after centuries of careful breeding. Cattle breeders are eagerly incorporating the information into their breeding programmes (see No bull: genes for better milk).
The project "is having a profound impact on the industry today", says Curt Van Tassel, a geneticist at the United States Department of Agriculture in Beltsville, Maryland, and a member of the consortium that did the work. "It has already paid for itself in the money that's going to be saved."
Cows (Bos taurus) were first domesticated up to 10,000 years ago. Now, the world's agricultural herds are teeming with 1.2 billion cattle, says Patrick Cunningham, an animal geneticist at Trinity College Dublin in Ireland and chief scientific adviser to the Irish government. Breeding programmes have had a dramatic effect on the populations, and by 2007, dairy herds in the United States were producing 34% more milk from about half as many cows as they were in 1960. "Economically, cattle are the most important partner species of animal we have," Cunningham says.
But the bovine genome is large — at 3 billion bases, it is roughly the same size as the human genome — making it difficult to study. In the absence of genomic information, breeding programmes have relied on tracking the physical characteristics of the animals, compiled in massive databases alongside detailed family trees, rather than harnessing genetic markers in the DNA sequence.
"We have very little knowledge of the genes that are involved in cattle breeding," says James Womack, a genome researcher at Texas A&M University in College Station, and another member of the consortium. "This opens the door to finding the genes that underlie important traits."
Dominette's genome sequence, published today in Science1, has also revealed a few genetic underpinnings of the bovine lifestyle. For example, Dominette has many copies of some of the genes involved in the innate immune system, which could reflect the heavy load of microbes she carries in her four-chambered stomach. Those bacteria are needed to break down grass and other delicacies in her fibrous diet, but could also pose an infection risk.
Researchers have also used the genome sequence to assemble a collection of more than 37,000 locations in the genome that contain frequent single-base changes in DNA sequence2. These genetic markers were then used to characterize the genetic diversity found in nearly 500 cattle from 19 breeds.
The results were surprising: although diversity has greatly decreased over time — as would be expected for an animal that has been domesticated and intensively bred for specific traits — the modern cattle population is about as diverse as humans, and much more diverse than dogs, says Kim Worley, a genome researcher at the Baylor College of Medicine in Houston, Texas, and a member of the bovine sequencing team.
This could be because the cattle populations that formed the basis for those first farmed herds were very diverse. But Harris Lewin, a genome biologist at the University of Illinois at Urbana-Champaign who also assisted with the analysis of the genome, suggests another explanation. Cattle may occasionally mated with aurochs — large, wild cows that lived in Europe until their extinction in the seventeenth century — providing periodic infusions of new genes, he says.
Despite this diversity, years of breeding cattle for meat and milk have weakened the herds, says Cunningham, which is evident in recent declines in longevity and fertility. Genetic markers will help breeders to improve the health of their herds as well as the quality and quantity of the food they produce by allowing them to track markers linked with, for example, longevity or milk production, without having to wait for calves to reach adulthood. Improved genetic techniques could push up agricultural yields by as much as 50% — or 12 gallons of milk — per cow each year, estimates Van Tassel.
The new sequence also shows that the human genome is more similar to the genome of cattle than to mice — suggesting that, for some diseases, cows could be a better model for research, says Lewin. In the past, work on cattle led to the development of the smallpox vaccine and in vitro fertilization techniques.
Geneticist Michel Georges of the University of Liège in Belgium worries that the focus on improving agricultural herds could cause researchers to stop investigating the biology underlying those improvements.
"There is more to be done with these domestic animal resources rather than just developing these genomic selection methods," says Georges. "It's a little bit sad if the scientific community does not really tap into that resource."
The Bovine Genome Sequencing and Analysis Consortium, Elsik, C. G., Tellam, R. L., & Worley, K. C. Science 324, 522-528 (2009).
The Bovine HapMap Consortium Science 324, 528-532 (2009).