Everyone Is African

by Daniel J. Fairbanks

  There are explainable exceptions to this general rule. For example, Native Americans in coastal regions of Alaska, northern Canada, Greenland, and northeastern Siberia—collectively known as Eskimo people—have lived in high-latitude, low-sunlight environments for thousands of years. Yet light skin complexions have not evolved there. In this case, the most probable reason also has to do with vitamin D. Diets in these regions since ancient times have been high in seal liver and fish, which naturally contain high amounts of vitamin D, compensating for reduced vitamin D production in the skin. With adequate vitamin D in the diet, reduced pigmentation did not confer a strong selective advantage.4

  Although rare, cases of rickets are still reported when people fail to consume a diet with sufficient vitamin D and when sunlight exposure is insufficient for adequate vitamin D production in the skin. This is especially true for infants, children, and adolescents, whose bodies are growing and require proportionally more vitamin D than adult bodies. The American Academy of Pediatrics recommends vitamin D supplementation in the diet to prevent rickets.5

  Skin damage resulting from overexposure to sunlight, however, remains a serious health issue. Sunlight-induced skin cancer does not explain why natural selection favored reduced skin pigmentation in northern regions (this type of cancer typically appears well after people have reproduced), but repeated exposure to sunlight can be a serious danger to individuals. Over time, it increases the probability of lethal skin cancer and other long-term skin disorders, especially for people whose skin complexions are light. Although skin pigmentation protects against sun damage, even high skin pigmentation is not an absolute protection. All people should protect themselves from overexposure to the sun. Nonetheless, light skin complexion is the highest genetic risk factor for malignant melanoma, the most serious and potentially lethal form of skin cancer.

  Having reviewed the main conclusions of research on how and why variation for pigmentation in humans originated, let's dig a bit deeper, examining some of the direct evidence of how this variation, and its geographic distribution, evolved throughout human history. To understand this variation, we need first to understand what skin pigmentation is.

  Human skin, hair, and eyes contain a group of related pigments called melanins, the prefix melan- meaning “dark” or “black.” The word melancholy, meaning a dark and somber mood, has the same root. Melanins ultimately arise from the food we eat—specifically, from the protein in our food. Each individual protein molecule is structured like a linked chain that, when stretched out, becomes linear. The links that make up each protein chain are called amino acids. When you eat anything with protein (which is in almost everything you eat), your digestive system breaks down each protein chain into the individual amino acids, which your digestive system then absorbs into the bloodstream. Your cells extract the amino acids from the blood and reassemble them into new chains in new combinations to form your own proteins.

  For instance, imagine eating a bowl of rice. The rice consists of seeds that contain mostly starch but also protein and a small amount of fat and fiber, along with trace amounts of vitamins and minerals. The natural function of proteins in rice is to provide a source of amino acids for a rice plant germinating from the seed so that the developing seedling can use the amino acids from those seed proteins to make its own proteins during its earliest growth stages. But by eating the rice seeds, you have co-opted those seed proteins for yourself. Your digestive system breaks down the rice proteins into individual amino acids, most of which end up in your bloodstream to be used by your cells to make proteins, such as the proteins that constitute much of your hair, fingernails, muscles, and blood. The proverb “You are what you eat” is correct, but it's more accurate to say, “You are a recombination of what you eat.”

  Although your cells use those amino acids to make your proteins, they divert some of them toward other purposes, one of which is to make melanins in the skin, hair, and eyes. Two amino acids—phenylalanine and tyrosine—are the starting points and are converted into melanins through a series of steps called a pathway. In each step of the pathway, one substance is chemically transformed into another substance. Figure 4.1 is a simplified depiction of some of the major steps in the melanin-synthesis pathway.

  Figure 4.1. Major steps of the melanin biosynthesis pathway.

  Genes in DNA govern each of the steps in the pathway, and those steps can only proceed when those genes are active and functioning. A mutation that causes a variant in any of these genes tends to reduce the activity of that gene, which, in turn, reduces the production of the melanins. The fact that these variants in DNA are inherited explains why the color of skin, hair, and eyes is inherited.

  Let's look first at some obvious examples of what happens when particular variants are inherited, starting with the second and third steps of the pathway: the conversion of tyrosine to DOPA, and DOPA into DOPAquinone. Variants affecting these two steps have the most dramatic inherited effect possible on pigmentation. The gene that governs these steps is called TYR, and variants that completely disable this gene cause albinism—more accurately, oculocutaneous albinism—which means those who have this form of albinism have no pigment in the skin, hair, and eyes. The hair is white, the skin has an extremely light complexion, and the irises in the eyes appear red or pink because, in the absence of melanins, the red color of the blood vessels is visible in the iris.

  Albinism is an uncommon inherited condition in humans, and it causes extremely high susceptibility to skin cancer and other related sunlight-exposure disorders, due to the absence of protective melanins in the skin. Mutations that cause albinism have occurred independently in humans at different times during human history and among various human cultures. Search the internet for images using the terms albinism and human, and you'll find dozens of photographs depicting people with albinism from various parts of the world.

  Albinism is also well known in many species of animals, such as albino rabbits, mice, and rats raised as pets or laboratory animals. They, too, have white hair and red or pink eyes. Albino reptiles, birds, and fish are also well documented. Not surprisingly, variants in the precisely the same gene (TYR) in humans and other animals cause albinism in all of them.

  After DOPAquinone, the pathway splits into two major branches that result in two major types of melanins: one called eumelanins, consisting of a group of dark bluish-brown pigments, and the other called pheomelanins, consisting of reddish-orange pigments. People who have blue eyes have reduced amounts of the bluish-brown eumelanins in the iris, hence the blue or bluish-green color. People who have what we call “red” hair carry one or more variants in their DNA that substantially reduce the bluish-brown eumelanins, so that the reddish-orange pheomelanins are the predominant pigment in the hair. (The same is true for reddish-orange coat color in orangutans, albeit by a different genetic process than in humans).6 Notably, most variants that result in red hair reduce eumelanins in not only the hair but also the skin and eyes. Hence, people with red hair often have light skin complexions and either blue or green eyes, although not always.7

  The wide range of pigmentation in humans is a consequence of variants in the numerous genes that regulate the pathway for melanin production. Each person carries a particular combination of variants in those genes, including ancestral variants that contribute to high pigmentation and, in many people, derived variants that reduce pigmentation. And the particular combination of variants a person carries determines the color of her or his skin, hair, and eyes. Because multiple genes regulate the various steps in the branching pathway for melanin synthesis, and because variations in any of these genes can influence melanin production, the inheritance of skin, hair, and eye color is highly varied and complex.

  But not too complex for scientists to decipher, especially with the research tools now available. Variants that reduce pigmentation in people from different parts of the world are now well documented, and, undoubtedly, others remain to be discovered. Those variants tell an intrigu
ing story, one that explains not only how variation for pigmentation arose but also why it is distributed throughout the world as it is.

  Let's look at some examples. Among the many variants that influence pigmentation in humans, not all are equal. Some confer major effects on pigmentation, whereas the effect of others may be relatively minor. Also, because pigmentation reduction is greatest in people whose ancestry derives from northern latitudes, much of the research on the genetic basis for pigmentation reduction has focused on variants that originated in European and east Asian populations. We'll look at several of the well-researched major variants and the times and places where these variants originated.8

  However, let's first turn to equatorial Africa, where the ancestral state of high skin pigmentation prevails. Is there any evidence in DNA that natural selection has preserved the highly pigmented skin of native Africans? Recall that sub-Saharan Africa is the region with the highest genetic variation in the world. Thus, we might expect that variation in the genes that govern skin pigmentation would be highest in people native to Africa. In fact, the opposite is true: the ancestral variants in genes governing skin pigmentation tend to be highly uniform in native Africans. As an example, the MC1R gene has a major effect on pigmentation, and variants in it are widespread throughout the world outside Africa, causing substantial reductions in pigmentation. For instance, one of these variants originated in what are now Scotland and the northern part of Ireland during an ice age when sea levels were lower and Ireland and Scotland were part of the same land mass. This variant results in very light skin complexion, freckling, and red hair and is most common in people whose ancestry traces to Ireland and Scotland.9 By contrast, the ancestral variant for MC1R is almost uniformly present in native Africans, in spite of high variation in genes unrelated to pigmentation. In equatorial Africa, variants that reduced pigmentation were eliminated through natural selection, and the original ancestral variants that conferred dark pigmentation were preserved.10 This type of natural selection—preservation of ancestral variants at the expense of derived variants—is called purifying selection, and it is common for many genes.

  It is often said that the increased risk of skin cancer is the reason why natural selection has favored dark skin pigmentation in equatorial parts of the world. The scientific evidence suggests, however, that skin cancer is not the reason for natural selection favoring highly pigmented skin. Although potentially lethal and a serious risk for people with light skin complexions, skin cancer typically appears later in life after many years of sun exposure, usually well after people have reproduced. For natural selection to be effective, it must preserve variants that confer an advantage for survival before reproduction. Its effect on preserving variants that reduce survival after reproduction is substantially minimized. In the case of equatorial Africa, the selection agent instead appears to be degradation of folate by high exposure to ultraviolet radiation in sunlight. A process called folate photolysis happens when folate in the skin is exposed to ultraviolet radiation and the folate is degraded. Folate is essential for fetal development, and insufficient folate often results in birth defects and fetal mortality, clearly influencing reproduction. High skin pigmentation has protected people in equatorial regions against folate degradation throughout human history.11

  Let's now turn our attention to variants that reduce pigmentation in people whose ancestry lies outside Africa. Recall that the out-of-Africa emigrations that founded non-African human populations took place about seventy thousand to sixty thousand years ago. The descendants of these original emigrants increased in number through numerous generations, and many of them began emigrating farther away from Africa. One group emigrated northward, eventually establishing settlements in an area near the Caucasus Mountains between the Black and Caspian Seas in what are now parts of the nations of Azerbaijan, Georgia, and Russia. This area became a major staging ground for subsequent immigrations into Asia and Europe, immigrations that founded the first human populations in these regions.

  Interestingly, the term Caucasian is derived from this region of ancient origins. The term itself, however, is less than scientific. As quoted by Stephen J. Gould in his book The Mismeasure of Man, Johann Friedrich Blumenbach explained his invention of the term Caucasian thusly: “I have taken the name of this variety [of humans] from Mount Caucasus, both because its neighborhood, and especially its southern slope, produces the most beautiful race of men, and because…in that region, if anywhere, we ought with the greatest probability to place the autochthones [original forms] of mankind.”12 These views—that so-called Caucasians were the “most beautiful race” and that humans originated in that part of the world—were generally accepted among Europeans and European Americans at the time (late 1700s in the case of Blumenbach), as well as for centuries before and after.

  Although Africa is undoubtedly the place where modern humans originated, the Caucasus region was a major center of secondary origin for the first European and east Asian populations. It is in this region that one of the oldest, most widespread, and most significant variants responsible for reduction in skin pigmentation appeared more than thirty thousand years ago. A mutation in a gene known as KITLG arose in one individual and was passed on as a variant to his or her offspring (there is no way to know whether the mutation happened in a female or a male). The variant that arose from this mutation reduced the skin color of those who inherited it, and it spread among the descendants of the individual in whom it first appeared.

  The derived variant differs from the ancestral variant only by a single base-pair substitution: an A–T pair in the ancestral variant mutated into a G–C pair in the derived variant:

  The origin of this derived variant before thirty thousand years ago predates the divergence of European and east Asian populations, and many people with ancestry from either of these regions now carry it. It also predates the climax of the most recent ice age, about twenty-four thousand to twenty-two thousand years ago. During this ice age, people who carried this variant had a distinct advantage for survival and reproduction as they migrated west into Europe or east into Asia. Because this variant was favored through natural selection in regions of lower sunlight, it is now most prevalent in people whose ancestry traces to Asia or Europe. In European populations, 84 percent of KITLG variants are this derived variant, and in east Asians, the percentage is similar at 82 percent. The ancestral nonmutant variant is still present in some people from these regions, but at low percentages. By contrast, the ancestral variant is by far the most common variant in indigenous African populations.

  Another derived variant that substantially reduces pigmentation is in the gene SLC24A5. The derived variant arose from a mutation that changed a G–C pair to an A–T pair in the DNA of this gene:

  The mutation that produced this variant arose between eleven thousand and nineteen thousand years ago in a person who lived somewhere between the Caucasus region and Europe and whose descendants immigrated into Europe, so this variant is most prevalent in people with European ancestry.13 The DNA sequences on both sides of it bear variants that portray the marks of a powerful selective sweep that caused its rapid spread among the descendants of ancient European immigrants. As a result, nearly 100 percent of people whose ancestry is entirely European carry this variant. In fact, it is a variant considered to be one of the most reliable ancestral informative markers for European ancestry. It is exceptionally rare in all other native populations.

  Because the derived variant is present in almost 100 percent of people whose ancestry is entirely or almost entirely European, it is not possible to tell how much it influences skin pigmentation by direct measurements in these populations; variation is essential to detect a correlation. However, most people whose ancestry is African American or Caribbean American have both African and European ancestry, so some carry two copies of this variant (inherited from both parents); some, one (inherited from one parent only); and others, none (not inherited from either parent). In these populations, t
he presence of this variant has a strong dosage effect on reduced skin pigmentation. Those who carry two copies of the ancestral variant have more pigmentation than those who carry one copy of the ancestral and one of the derived variant, and they have more pigmentation than those who carry two copies of the derived variant.

  Two other derived variants that also reduce the amount of skin pigmentation show a similar pattern to this one in that they are almost uniformly present in European populations and uniformly absent in African and east Asian populations, and they arose in Europeans at about the same time. They, too, result from single base-pair substitutions in two genes: SLC45A2 and TYRP1. Because the patterns are so similar, we'll not take the time to examine them in detail, other than to note that they, too, bear the hallmarks of selective sweeps that culminated in their high prevalence in ancient European populations.