The Sports Gene: Inside the Science of Extraordinary Athletic Performance (16 page)

Though natives have inhabited Iceland for just a single millennium, the company deCODE Genetics showed that it could identify which of eleven regions of Iceland a resident’s grandparents hailed from using just forty areas along the genome. In 2008, scientists looking at much larger swaths of DNA pinpointed the geographic ancestry of nearly all of a sample of three thousand Europeans to within a few hundred miles. And, to a degree, DNA can identify the construct we call “race” as well.

A 2002 study published by a team of researchers (including Kidd) in
Science
directed a computer to peruse 377 spots on the genomes of 1,056 people from around the world and then automatically separate the people into groups based on genetic differences. The groups that the computer delineated corresponded with the world’s major geographic regions: Africa, Europe, Asia, Oceania, and the Americas. A subsequent Stanford-led study asked 3,636 Americans to self-identify as either white, African American, East Asian, or Hispanic, and found that the self-identification matched a blind DNA identification in 3,631 cases. “This shows that people’s self-identified race/ethnicity is a nearly perfect indicator of their genetic background,” geneticist
Neil Risch said in a press release issued by the Stanford University School of Medicine.
*

Skin color, which is primarily determined by latitude, can be an imprecise marker of geographical ancestry, as there are spectrums of skin color on each continent. But geography and ethnic affiliation have most certainly left a trail of genetic crumbs.

In some areas of medicine, like pharmacogenetics—the study of how and why people with different genes respond differently to the same drugs—skin color is already being used as a proxy, albeit often a crude one, for underlying genetic information, and medical researchers now recognize the importance of testing the efficacy of drugs separately on different ethnic groups.

In 2004, Kidd and Tishkoff wrote that the main genetic and geographic clusters of people do “correlate with the common concept of ‘races,’” but added that if every population on earth were included, the genetic differences would look more like a continuous spectrum as opposed to a collection of discrete groups.

In 2009, Tishkoff and an international team published a landmark study that characterized the genetic backgrounds of African Americans. They found that adults who identify as African American are highly genetically diverse on the whole, with ancestry ranging from 1 percent to 99 percent West African. African Americans are particularly diverse in the amount of European ancestry they have in their DNA. But almost all African Americans were found to have African X chromosomes, consistent with the idea that the mothers of African Americans have historically been of very recent African ancestry, while fathers were sometimes African and sometimes European. The African Americans studied were from Baltimore, Chicago, Pittsburgh, and North Carolina, and the African components of their genetic ancestry showed “little genetic differentiation,” according to Tishkoff, and were similar
to one another and often to the genetic profiles of West African people like the Igbo and Yoruba of Nigeria; not a surprise, as the Igbo and Yoruba show up frequently in records of the slave trade as Africans who were wrenched from their homes and taken to the Caribbean and the United States.
*

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.

•

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 sprinters, 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.