One’s ancestry can be traced through one’s genes, but to go further down the path of Kidd’s thought experiment about African athletes, we must know not only that the genotypes of African people are the most diverse, but whether their phenotypes are also the most diverse. A phenotype is the physical manifestation of underlying genes. Geneticists still have scant clue what most of the billions of bases (each “letter” is one base) in our DNA do. Some may do little or nothing at all. Kidd’s suggestion is that because the greatest diversity of genotypes is contained in African populations, the greatest diversity of athletic phenotypes—both the slowest and the fastest runners—might also be there. So far, though, there is no easy, blanket conclusion to Kidd’s thought experiment.
In 2005, the U.S. government’s National Human Genome Research Institute weighed in on the issue of race and genetics and the question of whether most of the physical variation in the world occurs among individual people within ethnic groups, or among entire ethnic populations themselves. The institute directly addressed the question of whether the high degree of genetic diversity in African populations also means that most of the physical diversity in the world is contained in those populations. The answer: it depends on the specific physical trait you’re looking at.
About 90 percent of the variation in the shape of human skulls occurs within every major ethnic group—only 10 percent separates ethnicities—with Africans indeed showing the greatest variation. But the exact opposite is true for skin color: only 10 percent of the variation occurs within ethnic groups, and 90 percent of the difference is between groups. Thus, in order to discuss whether Africans or African Americans have specific genes that are advantageous in certain sports, scientists should first identify specific genes and innate biological traits that are important for sports performance, and then examine whether they occur more frequently in some populations than in others.
They have begun to do just that.
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Kathryn North had the letter to Nature Genetics all ready to go, and her report would be a breakthrough.
A few years earlier, in the summer of 1993, North had left Australia to train as a pediatric neurologist and geneticist at Boston Children’s Hospital, where she worked in a lab that had discovered the genetic mutation that causes Duchenne muscular dystrophy, a devastatingly virulent muscle-wasting disease. When North examined the muscle fibers of muscular dystrophy patients, she saw that they had a normal ration of fast-twitch muscle fibers, but that about one in five patients was missing a particular structural protein called alpha-actinin-3 that should have been in those explosive muscle fibers.
Her letter to Nature Genetics would document the case of two Sri Lankan brothers North examined in her lab in Sydney in 1998 and who had congenital muscular dystrophy. The brothers’ parents, who did not have the disease, were cousins, so the case appeared to be one of recessive genetic inheritance. Neither of the boys had any alpha-actinin-3, so North and colleagues sequenced in each boy the gene that codes for it, the ACTN3 gene. Sure enough, each boy had a “stop codon,” a genetic stop sign, at the same spot on both copies of the ACTN3 gene. The stop sign—just one single letter switch in the DNA—prevented the alpha-actinin-3 protein from being produced in muscles. North and her team, it appeared, had discovered a new gene mutation that caused muscular dystrophy. “I started drafting a letter to Nature Genetics, and I was literally drafting a paper to report a new disease gene,” she says. “But if you’re a good geneticist, you bring in the whole family.”
So North invited the parents and their other two, healthy children and probed their ACTN3 genes too. The version of the gene that the ill brothers had that stopped alpha-actinin-3 production is known as the X variant, and North expected the parents each to have one X variant, which they had passed to their sons, and one R variant, which functioned normally and facilitated production of the protein. To her surprise, both parents and the two healthy siblings also each had two X variants of the ACTN3 gene. Nobody in the family had any alpha-actinin-3 in their muscles whatsoever, yet only the two brothers had muscular dystrophy. North had not found a new muscular dystrophy gene after all. “That was a Friday when we found out,” she says, “and it was really, really depressing.”
That Sunday, she went to a movie and afterward took a walk to ponder the previous week. Never, not in the lab nor in the scientific literature, had she found an example of a healthy person with genes that left them entirely devoid of a structural protein. Structural proteins are critical. They make fingernails, hair, skin, tendons, and muscle. Humans tend to be diseased or to die when the genes that code for them are not functioning. “So I started reading the evolution literature,” North says, “and I thought, well, maybe alpha-actinin-3 is redundant. Maybe we don’t need it and it’s on its way out.”
North cold-called Simon Easteal, an Australian researcher with a specialty in molecular evolution. Together they yanked from storage two hundred samples of muscle with all manner of disease, from muscles that did not contract properly to others that had malfunctioning nerves. Just as she had seen with muscular dystrophy patients in Boston, about one in five of the diseased muscles had two copies of the X version of the ACTN3 gene, and thus no alpha-actinin-3. But about one in five samples of normal, healthy muscle had two X variants as well, so the gene could not be the cause of disease. Perhaps, then, alpha-actinin-3 had some other purpose in muscle. “That’s when we started to pull in different groups of people,” North says. “And that’s when we found this different ethnic distribution of the gene.”
North saw that one quarter of people of East Asian descent had two copies of the X variant of ACTN3 and about 18 percent of white Australians had two X variants. But when she tested Zulu people from South Africa, less than 1 percent had two X variants. Nearly all had at least one copy of the R variant, which codes for alpha-actinin-3 in fast-twitch muscle. And that was true of every African population. With respect to this particular gene variant, Africans or people of recent African ancestry happen to be extraordinarily uniform.
North was convinced that alpha-actinin-3 was not a meaningless protein, even though its absence did not lead to disease. Like the myostatin protein—of Superbaby fame—alpha-actinin-3 was highly conserved in evolutionary terms. It is in the explosive muscle fibers of chickens, mice, fruit flies, and baboons, among other animals, including our closest primate relatives, chimps. The absence of alpha-actinin-3, then, is a very recent and very human trait. North and colleagues estimated that the X variant spread through humans within the last thirty thousand years, and only outside of Africa. The gene, it appears, had been favored by natural selection only in non-African environments for some reason. Fast-twitch fibers must need it for something, North thought.
So she and her colleagues collected DNA from subjects with ample fast-twitch fibers: elite sprinters. They partnered with the Australian Institute of Sport to do ACTN3 testing on international-level athletes. While 18 percent of Australians had two X copies of the gene, almost none of Australia’s competitive sprinters did. Nearly every sprinter produced alpha-actinin-3 in their fast-twitch fibers. “I waited for years to publish that study,” North says. “The result came out the first time we did the analysis, and then we repeated it again and again internally.” And it held. Not only did sprinters in general tend not to have two X copies of ACTN3, but the better they were, the less likely it was they were XX. In one sample, just 5 out of 107 Australian sprinters were XX, and zero of the 32 sprinters who had gone to the Olympics were XX.
After that work was published, sports scientists around the world hustled to test their local sprinters, and the association showed up everywhere. With almost no exceptions, sprinters from Jamaica and Nigeria all had alpha-actinin-3 in their fast-twitch muscles, but so did distance runners from Kenya—no surprise given that nearly all of the control subjects from African populations did as well. Scientists in Finland and Greece took DNA from their Olympic sprinte
rs, and, again, not a single one was XX. In Japan, a few sprinters were XX, but none who had run faster than 10.4 seconds for 100 meters.
ACTN3, North concluded, is a gene for speed. Why that may be so is not exactly clear. Alpha-actinin-3 may have a structural impact on how explosively a muscle fiber can contract, or it may influence the configuration of the muscular system. Mice as well as—in several studies—Japanese and American women who are deficient in alpha-actinin-3 have smaller fast-twitch muscles and less muscle mass over all. When North bred mice to have no alpha-actinin-3, compared with normal mice they had far less active glycogen phosphorylase, the enzyme that mobilizes sugar for explosive actions, like sprinting. The fast-twitch muscle fibers in those mice also took on some of the properties of slow-twitch, endurance fibers.
Given the approximate timing of when the X version of ACTN3 appears to have spread through humans—fifteen to thirty thousand years ago—North has toyed with the idea that the variant may have proliferated during the last ice age. Absence of alpha-actinin-3 may make fast-twitch muscle fibers more metabolically efficient, like their slow-twitch neighbors, a boon, perhaps, in frigid, food-scarce northern latitudes outside of Africa. Two anthropologists have suggested that the X version may have spread when humans outside of Africa transitioned from the hunter-gatherer lifestyle to an agricultural one, where they would have had less need to sprint in war or hunting but more need to be metabolically efficient and to work at a steady rate for long hours.
But North is cautious. Though we share the vast majority of our DNA sequence with mice, genetically manipulated rodents are not ideal models of human genetic variation. “We don’t know the whole story,” North says. “Right now, it looks like ACTN3 is one gene that contributes a little to sprinting, and there may be hundreds, and of course there are other factors like diet, environment, and opportunity.”
Private gene-testing companies have been less circumspect. As soon as the ACTN3-and-Olympians study appeared, companies rushed into the sparsely regulated direct-to-consumer genetic testing market. Genetic Technologies, of Fitzroy, Australia, led the way. For $92.40, the company would tell a customer what versions of the ACTN3 gene they carry. (I have two R copies.) In 2005, the Manly Sea Eagles of Australia’s National Rugby League became the first team to admit publicly that it was testing players for ACTN3 and tailoring training programs accordingly, giving more explosive weight lifting and less cardio to the guys with sprinter variants.
Atlas Sports Genetics, of Boulder, Colorado, has made headlines for selling parents an ACTN3 test for their children. According to Kevin Reilly, president of Atlas, the test is particularly useful for “those younger athletes who don’t have the motor skills yet.” By “younger,” Reilly means that just because baby Kobe doesn’t know how to walk yet, that should not mean his DNA can’t begin charting his athletic career. If Kobe has no R versions of the gene, his parents can start nudging their little bundle of DNA toward endurance sports. The genetic-testing-in-diapers market barely materialized for Atlas, but the company did manage a preteen customer base. Says Reilly, “We have had some impact on athletes in the eight-to-ten age group,” in terms of influencing their sport choices.
Unfortunately for those eight-to-ten-year-olds, though, consumer genetic testing for athleticism is nearly worthless.* Scientists have increasingly realized that the inherited component of complex traits, like athleticism, is most often the result of dozens or even hundreds or thousands of interacting genes, not to mention environmental factors. If you are XX for the ACTN3 gene, “you probably won’t be in the Olympic 100-meters,” North says. But you already knew that, without a genetic test. Though the ACTN3 gene does appear to influence sprinting ability, making a sports decision based on it is like deciding what a puzzle depicts when you’ve only seen one of the pieces. You need that piece to complete the puzzle, but you certainly can’t see a meaningful picture without more pieces.
As Carl Foster, director of the Human Performance Laboratory at the University of Wisconsin–La Crosse and coauthor of several ACTN3 studies, puts it: “If you want to know if your kid is going to be fast, the best genetic test right now is a stopwatch. Take him to the playground and have him race the other kids.” Foster’s point is that, despite the avant-garde allure of genetic testing, gauging speed indirectly is foolish and inaccurate compared with testing it directly—like measuring a man’s height by dropping a ball from a roof and using the time it takes to hit him in the head to determine how tall he is. Why not just use a tape measure?
All that ACTN3 can tell us, it seems, is who will not be competing in the 100-meter final in Rio de Janeiro in 2016. And it is not even doing a very specific job of that, given that it is only ruling out about one billion of the seven billion people on earth.
Still, if only that one gene is taken into account, it is also telling us that there are almost no black people anywhere in the world who are ruled out.
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The Warrior-Slave Theory of Jamaican Sprinting
Welcome home again!” the black scientist says to the white scientist, a Cheshire Cat smile curling around his face.
The black scientist is Errol Morrison, the most renowned medical researcher in Jamaica. “Morrison Syndrome” is a form of diabetes that he linked to indigenous bush teas that some Jamaicans consume in copious quantities. Morrison is so esteemed on the island that once when he was receiving an award for his work, the doctor introducing him joked to the audience that when she traveled abroad people who learned she was from Jamaica would greet her with “Bob Marley!”—unless it was a diabetes conference, in which case they say, “Errol Morrison!”
Morrison is also the president of the twelve-thousand-student University of Technology in Kingston, known locally as UTech. And right now, in late March 2011, he’s joking with the white scientist, Yannis Pitsiladis, a biologist and obesity expert from the University of Glasgow who visits the island regularly and was recently made an adjunct distinguished professor in UTech’s nascent sports science program.
Now the men’s right hands are clasped, and each has his left around the other man’s back. There is a glistening affection between them. They will relax over dinner tonight in Morrison’s airy home, high on a hill, with the Kingston lights just pinpricks below.
But Pitsiladis is in town to work. For a decade now, he has been traveling here with cotton swabs and plastic containers asking for bits of cheek and gobs of drool from the planet’s fastest men and women. There is no place else on earth where he’s liable, over lunch, to bump into a half-dozen men and women who ran in the Olympic 100-meters. When he does, he will be sure to collect their DNA. (Once, during a chance encounter with a world-class runner at a social function, Pitsiladis hastily sterilized a wineglass for saliva collection.) UTech itself, with its humble, 300-meter grass track, is a hotbed for speed. Sprinters and jumpers who trained at UTech won more medals in track and field (eight) at the Beijing Olympics than dozens of entire countries won in the entire Games.
Over dinner, Morrison and Pitsiladis will talk about their shared scientific goal: untangling the factors, genetic and environmental, that have made a tiny island of three million into the world’s sprint factory. They have put their formidable brains together, and they have published papers together. They have also published separately on the topic in the scientific literature.
And the conclusions of those papers, on the issue of nature-or-nurture, could hardly be more opposite.
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In his memo pad for work-related expenses, Pitsiladis has a budget line for paying a witch doctor in Jamaica in his quest to get approval to collect DNA from the man’s community. Needless to say, there are few researchers like him in the world.
Pitsiladis’s ancestors left Greece after World War II in search of work, moving first to Australia, and then South Africa. From 1969, when he was two, Pitsiladis lived in the land of apartheid. In 1980, his family returned to Greece, to the i
sland of Lesvos, where he obsessed over training for a career as a professional volleyball player. The future biologist cut school to practice, but when he topped out at 5'10", Pitsiladis surrendered his volleyball dream. Both his previous lives, in South Africa and Greece, can be found embedded in the work he does now: looking for genes that make the planet’s best athletes, and asking whether one ethnicity has cornered the market on that precious DNA. For a decade, that has meant traveling to Ethiopia, Kenya, and Jamaica, to the training grounds of some of the most endurant and most explosive athletes on earth.
The work has been arduous. Time and again, Pitsiladis has been denied funding to examine the genes of athletes, as research funding for human genetics is generally earmarked for the study of human ancestry or health and disease. So Pitsiladis sustains his academic position at the University of Glasgow by studying the genetics of childhood obesity, a line of inquiry that attracts hefty grants. Pitsiladis’s dean at Glasgow has made a point of telling him to ditch the athlete work and focus on his obesity research. But Pitsiladis is maniacal about his research passion, and obesity genetics is not it.
“I just published a paper on a fat gene,” he says, “but [the gene] has a very small effect, and that can be overcome with physical activity. And we’ll find many more genes, and already I can tell you what the answer will be.” He holds up his thumb and forefinger, an inch apart. He’s indicating that although scientists will find dozens, or hundreds, or thousands of DNA variations that contribute to a predisposition for being overweight, they will all amount to only a small fraction of the explanation for the industrialized world’s obesity epidemic.
It is as if Pitsiladis peels off a dour mask when he switches from discussing obesity genetics to his other work: peering into the genes of the greatest athletes in the world. He occasionally dons a gold and green Ethiopia track-and-field shirt, a gift from an Ethiopian gold medalist, and strands of salt-and-pepper hair bounce off his temples when he gets excited. His eyelids peel back, and his delicate accent, an amalgam of the countries where he has lived, leaps to mezzo-soprano. “My brain never switches off this topic,” he says. “It never stops. Never. I once worked for a year to get one DNA sample! Who else is going to do that?” The answer, in sports science: no one, because there is scant funding for it.
The Sports Gene: Inside the Science of Extraordinary Athletic Performance Page 17