A moment ago, we discussed the derived variant in the gene KITLG, which appeared early in what is called a proto-Eurasian population before the divergence of European and east Asian migrants. Thus, it reduces skin pigmentation in large proportions of people whose ancestry is either European or east Asian. Other, more recent, variants also reduce pigmentation in east Asian populations, and they are entirely independent of those in European populations.
Perhaps the best-studied example is a derived variant in the gene OCA2, which has one of the most significant and widespread pigment-reducing effects in people of east Asian ancestry. A mutation changed an A–T pair in the ancestral DNA to a G–C pair in the derived variant:
This variant is common in east Asian populations, and, like other such variants, the DNA surrounding it bears the evidence of it being favored through natural selection.
The observation that natural selection has independently favored different pigment-reducing variants in European and east Asian populations is an excellent example of what biologists call convergent evolution. It results when the same external characteristic evolves independently in different populations when those populations are subjected to similar environmental conditions. The underlying variants responsible for that characteristic usually are different in those populations, as is the case here, because the mutations happen independently. In other words, the response to natural selection is the same in different populations, but the genetic basis is different.
Although this particular variant is east Asian in origin, some people of European ancestry also carry a different variant in this same gene (OCA2), and its origin is independent of the east Asian variant. Genes are long strings of base pairs in DNA, and a mutation can happen anywhere in a gene. Hundreds or even thousands of different variants in a single gene are possible when the world's entire human population is considered. Other independent pigment-reducing variants are known in east Asian populations, including major pigment-reducing variants in the genes DCT and ATRN, evidence that the genetic basis for pigment reduction in east Asian populations is complex and due to variants in several genes.
One of the most intriguing examples of convergent evolution for skin pigmentation, however, comes from Neanderthals. In modern humans, several derived variants in the MC1R gene are known to substantially reduce eumelanins, resulting in red hair and very light skin pigmentation, often with freckling. Variants in this gene are especially common in people with Irish, English, and Dutch ancestry, due to mutations that happened anciently in people living in northern Europe, and they cause red hair, as mentioned earlier in this chapter.14 In 2007, scientists from Spain, Italy, Germany, and France discovered that DNA from the remains of a Neanderthal man, found in the Italian Alps, contains a variant in this same gene that should have substantially reduced eumelanin production in this man.15 According to their analysis, this Neanderthal man probably had red hair and very low skin pigmentation, the same as in humans today who inherit similar derived variants of this gene. Thus, natural selection may have favored low skin pigmentation in at least some Neanderthals who lived in regions of Europe with low winter sunlight. Although this variant is in the same gene as pigment-reducing variants in modern humans whose ancestry traces to Ireland and Scotland, this particular variant has never been found in modern humans and is probably exclusive to Neanderthals. It therefore must have arisen separately and independently, an example of convergent evolution for reduced skin pigmentation in Neanderthals and modern humans. Interestingly, the ancestral variant for this gene has since been discovered in DNA from other Neanderthals, suggesting they may have had greater pigmentation in their skin, hair, and eyes than this individual—evidence that pigmentation varied in Neanderthals, as it varies in modern humans.16
The ability to tan when exposed over a period of days to increased sunlight is also an inherited characteristic that has evolved through natural selection. The lightest complexions have evolved in extreme northern regions, such as Scandinavia, northwestern Russia, the British Isles, and Ireland. In these regions, winter sunlight is brief, and summer sunlight, though extended through long days, is not as intense as elsewhere in the world because of the sharper angle of the sun's rays relative to the surface of the earth. People with ancestry entirely or predominantly from these regions often sunburn easily and are unable to tan. Their extremely light skin complexions are an excellent adaptation to their region of ancestry because such complexions facilitate vitamin D production with low sun exposure. At more intermediate latitudes, a relatively light skin complexion during winter, when sunlight is weak, and a darker complexion during summer, when sunlight is intense, provide the combination of exposure and protection that is needed to facilitate the tradeoff between vitamin D production and protection against folate degradation. The ability of people whose ancestry traces to intermediate latitudes to tan allows their skin to adapt to seasonal changes in sunlight. Some people have argued that the gradually increasing exposure to light required for tanning is not a particularly good adaptation because it requires so much time and initially does not prevent skin damage. In response, Nina Jablonsky and George Chaplin of the University of Pennsylvania wrote,
Tanning is viewed by modern clinicians as an imperfect adaptation to UVR because it damages the skin's connective tissues, immune system, and DNA, and thus leads to progressive changes resulting in skin cancer. This is an appropriate statement for vagile and longevous 21st century humans but not for those of the 18th century or earlier who lived before the advent of widely available, rapid long-distance transportation. With early reproduction and before the extension of the average human lifespan through improvements in diet and medicine, skin cancer had no effect on reproductive success. Further, the genetic pattern of skin cancer risk does not accord with predictions based on selection for resistance to skin cancer. In the context of human evolution, the evolution of tanning was a superb evolutionary compromise.17
To conclude, in spite of the complexities of the genetic basis for skin color variation in humans, the inferences from scientific research are straightforward and unambiguous. Intense skin pigmentation is the ancestral state of humanity, and it traces to the original African origin of all humans. Variants conferring reduced skin pigmentation are strongly associated with ancient immigration during the most recent major ice age into Europe and east Asia, regions of low winter sunlight. People who inherited these variants had a survival and reproductive advantage in these regions because they were better able to produce vitamin D than people with higher skin pigmentation. By contrast, high skin pigmentation was advantageous to people who lived in regions of intense year-round sunlight nearer the equator because of the protective effect against folate degradation, which adversely affects fetal development. Many of the variants responsible for reduced skin pigmentation have been identified in people of European and east Asian ancestry, and they bear the molecular signatures of natural selection, including selective sweeps that rapidly increased the prevalence of these variants.18
Returning to Martin Luther King's words that opened this chapter, we have not yet reached the day when people are no longer “judged by the color of their skin.” There is no evidence whatsoever from science to justify discrimination on the basis of skin color. On the contrary, science has given us a clear understanding of why variation for skin, hair, and eye pigmentation is such an obvious indicator of human diversity, and it has nothing to do with notions of superiority or so-called racial purity. Instead, it is clearly tied to our evolutionary history and the effects of natural selection, aspects of human diversity that should evoke a sense of wonder for the forces of nature that have shaped our past and present.
The afternoon of September 24, 2006, was hot and humid in Houston, Texas, not unusual for that time of year. It was the day after a Rice University football game, and those members of the team who had played in little or none of the game, mostly underclassmen, participated in a practice session with vigorous weight training and sixteen consecutiv
e hundred-yard sprints. One of the players who practiced that afternoon was a nineteen-year-old defensive back who collapsed and lost consciousness after the final sprint. The following day, he died. Subsequent tests showed that he had sickle-cell trait, a typically benign genetic condition that manifests symptoms only rarely, if at all. When symptoms do appear, the trigger is usually a combination of extreme physical stress, heat exhaustion, and dehydration. In rare cases, the symptoms are severe and sometimes fatal, as in this tragic instance.
This young man was African American. Although sickle-cell trait occurs in people with many different ancestral backgrounds, it is most frequent in people with African ancestry. A derived variant in a gene called HBB is responsible for the condition:
The reason for its relatively high prevalence in people with recent African ancestry is one of the most extensively researched and best-documented examples of natural selection in humans, with evidence dating back to 1954.1 The ancestral variant is usually designated as A and the derived variant as S. Humans inherit two copies of each gene, one from each parent, so each person has one of three possible combinations of the A and S variants: AA, SS, or AS. In genetic terms, people who inherit the same variant from both parents (SS or AA) are said to be homozygous, whereas those who inherit different variants (AS) are heterozygous. People who are homozygous SS suffer from a serious genetic condition called sickle-cell anemia, characterized by severe fatigue due to a lack of functional red blood cells; intense pain, especially in the joints; swollen hands and feet; spleen damage, resulting in frequent infections; and damage to the retinas in the eye, resulting in impaired vision. Prior to modern medicine, it was often fatal during childhood or adolescence, but with current treatments, people who have it may live much-extended lifespans, although not without significant pain and suffering. Those who are heterozygous AS have sickle-cell trait (not sickle-cell anemia), and most never know they carry it because symptoms are usually nonexistent. The two conditions—sickle-cell anemia (SS) and sickle-cell trait (AS)—are often collectively referred to as sickle-cell disease.
The reason the S variant is more common in people with African ancestry has to do with recent human evolution and malaria, a devastating infectious disease caused by a microscopic parasite transmitted into the blood through mosquito bites. There are several types of malaria, each caused by a slightly different species of the parasite. The parasite species Plasmodium falciparum causes the most severe form of malaria, and nowhere in the world is this type of severe malaria more prevalent than in tropical Africa.
To best understand the relationship between severe malaria and sickle-cell trait, we need to go back more than two million years in human evolutionary history. There were no anatomically modern humans at that time, and our humanlike ancestors lived exclusively in Africa. They were susceptible to a milder form of malaria—not the severest form that now plagues humans, but nonetheless serious enough to cause illness and death. Chimpanzees continue to suffer from this milder form, but humans today are immune to it. A mutation in a different gene (CMAH) in one of our ancient ancestors produced a variant that conferred complete immunity to this milder form of malaria. Natural selection favored this variant in our ancestors until it eventually was the only variant present in ancient humans, the original ancestral variant having disappeared entirely. All humans alive today are homozygous for this protective variant in the CMAH gene and are immune to the form of malaria that still infects chimpanzees.
However, immunity to malaria would not last. The parasite that causes malaria is a living organism with its own DNA, so variants within its DNA that increase its ability to infect humans may be favored through natural selection. Over a period of nearly two million years, several variants accumulated in the ancient malarial parasite's DNA that allowed a new species to evolve, one that infects only humans: Plasmodium falciparum. This new species overcame the genetic immunity that had protected our ancestors. The final mutation in the parasite happened quite recently, between five thousand and ten thousand years ago, after humans had spread throughout the world.2 This newly evolved parasite now causes the severest form of malaria. It is exclusive to humans, and it is the most common type of malarial infection today.
The S variant confers resistance to infection by this parasite, especially in young children, so people who carry one copy of the S variant (AS)—in other words, who have sickle-cell trait—are more resistant to malaria than those who carry two copies of the ancestral variant (AA). In temperate regions of the world where malaria is absent or rare, the S variant confers little or no advantage. In fact, throughout most of human history, it was disadvantageous in temperate regions. Without the modern medical treatments now available, children who had sickle-cell anemia (SS) often died before they could reproduce and pass on the S variant to children. In regions such as equatorial Africa, however, where malaria is endemic, people with sickle-cell trait (AS) had an advantage for survival and reproduction because they were resistant to malaria. And their offspring who inherited one copy of the S variant (AS) also had the same advantage.
Throughout several thousand years in Africa, and, to a lesser extent, in the Arabian Peninsula, south Asia, and the Mediterranean region, natural selection favored the S variant in people who had sickle-cell trait, maintaining a relatively high prevalence of the S variant. Hence, people today whose ancestry derives from regions where malaria historically was prevalent are more likely to carry the S variant and have sickle-cell trait. Also, sickle-cell anemia is more common in people whose ancestries trace to these regions, although much less common than sickle-cell trait because the probability of inheriting the S variant from both parents (who must both be AS for this to happen) is less than inheriting it from just one.
There is solid evidence that the S variant originated several times independently in Africa—in one case, less than 2,100 years ago.3 And the S variant present in people whose ancestry is from a region stretching from the Arabian Peninsula to south Asia originated from yet another independent mutation.4 Each time the S variant arose from mutation in an area where malaria was endemic, natural selection promoted an increase in its prevalence. Therefore, this variant is not purely African in origin, only more frequent in people with African ancestry. Also, importantly, not everyone with African, Arabian, or south Asian ancestry carries the S variant; in fact, just a small minority do, so having ancestry from one of these regions is no guarantee that someone carries the S variant, only a somewhat increased probability compared to people who do not have ancestry from these regions.
Sickle-cell trait is an example of how evolutionary history can become entangled in modern racial tensions. After the tragic death of the young man mentioned at the beginning of this chapter, his family discovered that he was not the first athlete to die from complications of sickle-cell trait after a strenuous practice; several African American collegiate athletes who had sickle-cell trait had previously died under similar circumstances. Quite a few people argued that had he and the others been tested and their health status made known, they probably would not have been subjected to the strenuous conditions that ended up taking their lives. His family sued Rice University and the National Collegiate Athletic Association (NCAA). Families of other athletes sued as well. Eventually, after legal settlements, the NCAA implemented rules regarding testing for sickle-cell trait. Beginning in 2010, the NCAA required all collegiate athletes, regardless of their ancestral background, to be tested for sickle-cell trait, provide evidence that they have already been tested, or sign a waiver releasing liability should they choose not to be tested.
The rule immediately sparked controversy, including stern warnings from reputable scientific organizations about its potential for racial discrimination. According to an official statement issued in 2012 by the American Society of Hematology, representing more than sixteen thousand physicians and scientists specializing in blood diseases, “the NCAA policy attributes risk imprecisely, obscures consideration of other relevant risk factors,
fails to incorporate appropriate counseling, and could lead to stigmatization and racial discrimination.”5 This scientific society recommended instead “the implementation of universal interventions to reduce exertion-related injuries and deaths, since this approach can be effective for all athletes irrespective of their sickle cell status.”6 According to a statement by the Sickle Cell Disease Association of America, the current NCAA requirement “carries great risk of stigmatization and discrimination against athletes with sickle cell trait. The NCAA mandate for sickle trait screening does not provide adequate assurance of the privacy of genetic information nor protection from the discriminatory use of such information.”7
The US Army had faced a similar situation. Research on the rare deaths of recruits during basic military training revealed a higher incidence of deaths for those who had sickle-cell trait than for those who did not.8 Notably, most recruits with sickle-cell trait passed basic training without incident, and a few who did not have sickle-cell trait also died from overexertion. Sickle-cell trait merely increased the statistical likelihood of death due to overexertion. In response, the army altered its protocols for basic training to better protect all soldiers from risks associated with overexertion, heat exhaustion, and dehydration, regardless of their sickle-cell status. In fact, no branch of the US military currently tests for, or requests information about, a recruit's sickle-cell status. Large numbers of Brazilian citizens also have African ancestry, with a somewhat higher incidence of sickle-cell trait. The Brazilian Army has implemented a similar policy to protect all soldiers from overexertion and does not test them for sickle-cell trait. The American Society of Hematology has recommended that collegiate athletic programs do the same.
Everyone Is African Page 8
