* * *
Amidst this progress, the USDA scientists also noticed something odd. To understand how odd, you just need to know that animals have two copies of every gene, one from each parent. As Chief’s genes took over the Holstein population, farmers would sometimes end up mating a bull and cow both originally descended from Chief. So a resulting calf could sometimes end up with two identical copies of a Chief gene, one inherited via its mother (perhaps a great-granddaughter of Chief) and one via its father (perhaps a great-grandson).
But there was one particular gene from Chief that never, ever showed up twice in any of his descendants. Plenty of cows had one copy of this Chief gene; others none; but never two. This defied probability. All the USDA team knew about this gene is that it corresponded to a series of genetic markers on chromosome 5, which could be traced back to Chief.
The logical conclusion to draw, if you’re a geneticist, is that these genetic markers corresponded to a vital gene that had become garbled. Cow embryos with one faulty copy of the gene and one working copy grew up just fine, but those with two faulty copies died in the womb. They were just never born, which is why the team could never find any. (Chief himself had one copy, which why he was a fine healthy, bull.) That loss is double whammy for dairy farmers, because a cow that miscarries does not produce milk and, of course, the unborn calf did not grow up to be a dairy cow.
The USDA team now knew something was wrong with this segment of Chief’s DNA, but they didn’t know exactly where or why. Remember, the USDA was working with genetic markers, which did not actually get at the underlying DNA sequence. So they called up Harris Lewin, who had, by chance, undertaken the then-enormously-expensive project of sequencing Chief’s entire genome a few years ago. Chief and his son Walkway Chief Mark were the first two dairy bulls to ever be sequenced.
Lewin and his post doc Heather Adams got to work. “Within 48 hours, we had a candidate,” he says. The stretch of DNA in question corresponded to the gene Apaf1, which had been well studied in mice. Brain cells in mice embryos with a faulty Apaf1 would grow out of control, until the embryo eventually died. “The reason we had a candidate so quickly was because of the tremendous investment in mouse genetics,” says Lewin. The scientists trudging through the mouse genome could probably have never known an obscure gene they isolated had such a huge effect on the dairy industry.
So why did it take decades for anyone to notice the Apaf1 mutation in cows? One answer is that it took a while before there was anything to notice. Cows, humans, dogs, spiders—we all have garbled copies of genes hiding inside us, but as long as we only have one copy, everything’s fine. It’s only when a rare lethal mutation ends up on both sides of the family that it causes problems. In other words, it’s only when Chief’s descendants took over the Holstein population that Apaf1 started causing miscarriages. “It’s really inbreeding that causes these defects,” says Sonstegard. While selective breeding has increased the productivity of dairy cows, it’s also increased the genetic similarity of the population.