It started with a bull named Pawnee Farm Arlinda Chief, who had a whopping 16,000 daughters. And 500,000 granddaughters and more than 2 million great-granddaughters. Today, in fact, his genes account for 14 percent of all DNA in Holstein cows, the most popular breed in the dairy industry.
Chief—let’s call him Chief for brevity’s sake—was so popular because his daughters were fantastic milk producers. He had great genes for milk. But, geneticists now know, he also had a single copy of a deadly mutation that spread undetected through the Holstein cow population. The mutation caused some unborn calves to die in the womb. According to a recent estimate, this single mutation ended up causing more than 500,000 spontaneous abortions and costing the dairy industry $420 million in losses.
That’s a crazy number, but here’s an even crazier one: Despite the lethal mutation, using Chief’s sperm instead of an average bull’s still led to $30 billion dollars in increased milk production over the past 35 years. That’s how much a single bull could affect the industry.
Chief embodies the power and the perils of selective breeding, which has made tremendous gains for the dairy industry. The average cow today produces four times as much milk as one from the 1960s. And over the past decade, the dairy industry has embraced big data, sequencing thousands of dairy cows to pinpoint the genetic markers that correlate with prodigious milk production. It took some clever geneticists to realize they could also look for bad genes that have been lurking undetected.
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Chief was so influential because he was lucky—genetically blessed and born at the right time in the right place. His birth in 1962 coincided with the rise of artificial insemination. Dairy scientists were figuring out how to harvest and freeze sperm, freeing cow procreation from the limits of time and space. Chief’s sperm was collected, frozen, and mailed out to farms across the country. Chief and his son Walkway Chief Mark were “two of the most historically important bulls in the history of the Holstein breed,” says Harris Lewin, a geneticist at the University of California, Davis. Dairy farmers could buy semen based on the reputation of the bulls, and milk production shot up.
About a decade ago, researchers at the U.S. Department of Agriculture decided to up the game even more. The traditional way to test the potential of a bull was to “prove” it: Wait for him to reach sexual maturity, mate him with several cows, wait for his daughters to grow up, mate his daughters, and finally test their milk production. (Cows, like humans, only produce milk after giving birth.) Scientists would take those milk production numbers along with a few other factors like longevity and udder shape to calculate “net merit,” an all-encompassing metric used to rank bulls by how much value their genes add to their daughter cows. The process took years.
New ways to analyze DNA changed that. The USDA worked with the biotech company Illumina to create a test for genetic markers at 50,000 locations in the cattle genome. Then they combined the genetic marker data with milk production data. The test doesn’t actually tell breeders the sequence of the underlying genes, but it lets them know that at location A, B, and C are markers correlated with desirable traits. By pulling this data together, they could predict a young bull’s net merit using DNA alone.
These genetic-marker tests are far cheaper than proving a bull. “You could spend a quarter million testing 10 bulls to have one graduate for semen production,” says Tad Sonstegard, chief scientific officer of the livestock genetics company Acceligen, who previously had also worked on DNA tests while at the USDA. “Or you could test hundreds of bulls for about a couple hundred dollars a piece.”
And more importantly, it saved time. Since farmers no longer had to spend years proving a bull, they could put a top-notch sire into semen production at 10 months old. This meant that farmers could now breed two generations of dairy cows in the time it once took to breed one—doubling the pace of improvement in dairy cow genetics. Things are changing so fast that a top-ranking bull today doesn’t stay at on top for long. “Within a year, he’s already old news,” says Duane Norman, a technical adviser for the Council on Dairy Cattle Breeding.
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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.
And frankly, Chief’s other genes were so good, so productive, that they masked the downsides of Apaf1. It didn’t matter in the intense race to produce more milk. In recent years, dairy cow breeding has gone for a more balanced selection of traits—easing the pedal on milk production and taking into account more factors like cow health.
With the identification of Apaf1, breeders can now screen against it. In fact, they were already doing it—based on the genetic-marker data which allowed breeders to have a rough idea of whether Chief’s descendant carried the faulty gene. But identifying the exact location of the gene allows for more precise selection. (Genetic markers can sometimes move around.) The frequency of this faulty gene has fallen from 8 percent to 2 percent, and it may soon go all the way down to zero.
Genetics has transformed breeding in the dairy industry, making it easier to spot patterns like Apaf1’s lurking in the genetic pool. And dairy cows will become better and better optimized milk-making machines. Chief, so exceptional in his age, has been superseded by his genetically superior descendants. As Norman puts it, “A bull with a birthdate of 1962 doesn’t have a prayer competing against today’s animals.”