Page 40 of The Gene


  Where did the first modern humans come from? By 1991, Wilson could use his method to reconstruct the lineage relationship between various populations across the globe and calculate the relative age of any population using genetic diversity as his molecular clock. As gene-sequencing and annotation technologies evolved, geneticists refined this analysis—broadening its scope beyond mitochondrial variations and studying thousands of individuals across hundreds of populations around the world.

  In November 2008, a seminal study led by Luigi Cavalli-Sforza, Marcus Feldman, and Richard Myers from Stanford University characterized 642,690 genetic variants in 938 individuals drawn from 51 subpopulations across the world. The second startling result about human origins emerges from this study: modern humans appear to have emerged exclusively from a rather narrow slice of earth, somewhere in sub-Saharan Africa, about one hundred to two hundred thousand years ago, and then migrated northward and eastward to populate the Middle East, Europe, Asia, and the Americas. “You get less and less variation the further you go from Africa,” Feldman wrote. “Such a pattern fits the theory that the first modern humans settled the world in stepping-stone fashion after leaving Africa less than 100,000 years ago. As each small group of people broke away to found a new region, it took only a sample of the parent population’s genetic diversity.”

  The oldest human populations—their genomes peppered with diverse and ancient variations—are the San tribes of South Africa, Namibia, and Botswana, and the Mbuti Pygmies, who live deep in the Ituri forest in the Congo. The “youngest” humans, in contrast, are the indigenous North Americans who left Europe, and crossed into the Seward peninsula in Alaska through the icy cleft of the Bering Strait, some fifteen to thirty thousand years ago. This theory of human origin and migration, corroborated by fossil specimens, geological data, tools from archaeological digs, and linguistic patterns, has overwhelmingly been accepted by most human geneticists. It is called the Out of Africa theory, or the Recent Out of Africa model (the recent reflecting the surprisingly modern evolution of modern humans, and its acronym, ROAM, a loving memento to an ancient peripatetic urge that seems to rise directly out of our genomes).

  The third important conclusion of these studies requires some conceptual background. Consider the genesis of a single-celled embryo produced by the fertilization of an egg by a sperm. The genetic material of this embryo comes from two sources: paternal genes (from sperm) and maternal genes (from eggs). But the cellular material of the embryo comes exclusively from the egg; the sperm is no more than a glorified delivery vehicle for male DNA—a genome equipped with a hyperactive tail.

  Aside from proteins, ribosomes, nutrients, and membranes, the egg also supplies the embryo with specialized structures called mitochondria. These mitochondria are the energy-producing factories of the cell; they are so anatomically discrete and so specialized in their function that cell biologists call them “organelles”—i.e., mini-organs resident within cells. Mitochondria, recall, carry a small, independent genome that resides within the mitochondrion itself—not in the cell’s nucleus, where the twenty-three pairs of chromosomes (and the 21,000-odd human genes) can be found.

  The exclusively female origin of all the mitochondria in an embryo has an important consequence. All humans—male or female—must have inherited their mitochondria from their mothers, who inherited their mitochondria from their mothers, and so forth, in an unbroken line of female ancestry stretching indefinitely into the past. (A woman also carries the mitochondrial genomes of all her future descendants in her cells; ironically, if there is such a thing as a “homunculus,” then it is exclusively female in origin—technically, a “femunculus”?)

  Now imagine an ancient tribe of two hundred women, each of whom bears one child. If the child happens to be a daughter, the woman dutifully passes her mitochondria to the next generation, and, through her daughter’s daughter, to a third generation. But if she has only a son and no daughter, the woman’s mitochondrial lineage wanders into a genetic blind alley and becomes extinct (since sperm do not pass their mitochondria to the embryo, sons cannot pass their mitochondrial genomes to their children). Over the course of the tribe’s evolution, tens of thousands of such mitochondrial lineages will land on lineal dead ends by chance, and be snuffed out. And here is the crux: if the founding population of a species is small enough, and if enough time has passed, the number of surviving maternal lineages will keep shrinking, and shrinking further, until only a few are left. If half of the two hundred women in our tribe have sons, and only sons, then one hundred mitochondrial lineages will dash against the glass pane of male-only heredity and vanish in the next generation. Another half will dead-end into male children in the second generation, and so forth. By the end of several generations, all the descendants of the tribe, male or female, might track their mitochondrial ancestry to just a few women.

  For modern humans, that number has reached one: each of us can trace our mitochondrial lineage to a single human female who existed in Africa about two hundred thousand years ago. She is the common mother of our species. We do not know what she looked like, although her closest modern-day relatives are women of the San tribe from Botswana or Namibia.

  I find the idea of such a founding mother endlessly mesmerizing. In human genetics, she is known by a beautiful name—Mitochondrial Eve.

  In the summer of 1994, as a graduate student interested in the genetic origin of the immune system, I traveled along the Rift Valley, from Kenya to Zimbabwe, past the basin of the Zambezi River to the flat plains of South Africa. It was the evolutionary journey of humans in reverse. The final station of the journey was an arid mesa in South Africa, roughly equidistant from Namibia and Botswana, where some of the San tribes once lived. It was a place of lunar desolation—a flat, dry tabletop of land decapitated by some geophysically vengeful force and perched above the plains below. By then, a series of thefts and losses had whittled my possessions down to virtually nothing: four pairs of boxers, which I often doubled up and wore as shorts, a box of protein bars, and bottled water. Naked we come, the Bible suggests; I was almost there.

  With a little imagination, we can reconstruct the history of humans using that windblown mesa as a starting point. The clock begins about two hundred thousand years ago, when a population of early modern humans begins to inhabit this site, or some such site in its vicinity (the evolutionary geneticists Brenna Henn, Marcus Feldman, and Sarah Tishkoff have pinpointed the origin of human migration farther west, near the coast of Namibia). We know virtually nothing about the culture and habits of this ancient tribe. They left no artifacts—no tools, no drawings, no cave dwellings—except the most profound of all remnants: their genes, stitched indelibly into our own.

  The population was likely quite small, even minuscule by contemporary standards—no more than about six thousand or ten thousand individuals. The most provocative estimate is a bare seven hundred—about the number of humans that might inhabit a single city block or a village. Mitochondrial Eve may have lived among them, bearing at least one daughter, and at least one granddaughter. We do not know when, or why, these individuals stopped interbreeding with other hominids—but we do know that they began breeding with each other with relative exclusivity about two hundred millennia ago. (“Sexual intercourse began,” the poet Philip Larkin once wrote, “in nineteen sixty-three.” He was off by about two hundred thousand years.) Perhaps they were isolated here by climate changes, or stranded by geographic barriers. Perhaps they fell in love.

  From here, they went west, as young men often do, and then traveled north.II They clambered through the gash of the Rift Valley or ducked into the canopies of the humid rain forests around the Congo basin, where the Mbuti and Bantu now live.

  The story is not as geographically contained or as neat as it sounds. Some populations of early modern humans are known to have wandered back into the Sahara—a lush landscape then, crisscrossed with finger lakes and rivers—and eddied backward into local pools of humanoids, coexis
ted and even interbred with them, perhaps generating evolutionary backcrosses. As Christopher Stringer, the paleoanthropologist, described it, “In terms of modern humans, this means that . . . some modern humans have got more archaic genes than others. That does seem to be so. So it leads us on to ask again: what is a modern human? Some of the most fascinating ongoing research topics in the next year or two will be homing in on the DNA that some of us have acquired from Neanderthals. . . . Scientists will look at that DNA and ask, is it functional? Is it actually doing something in the bodies of those people? Is it affecting brains, anatomy, physiology, and so on?”

  But the long march went on. Some seventy-five thousand years ago, a group of humans arrived at the northeastern edge of Ethiopia or Egypt, where the Red Sea narrows to a slitlike strait between the shrugged shoulder of Africa and the downward elbow of the Yemeni peninsula. There was no one there to part the ocean. We do not know what drove these men and women to fling themselves across the water, or how they managed to cross it (the sea was shallower then, and some geologists have wondered whether chains of sandbar islands spanned the strait along which our ancestors hopscotched their way to Asia and Europe). A volcano had erupted in Toba, Indonesia, about seventy thousand years ago, spewing enough dark ash into the skies to launch a decades-long winter that might have precipitated a desperate search for new food and land.

  Others have proposed that multiple dispersals, prompted by smaller catastrophes, may have taken place at various times in human history. One dominant theory suggests that at least two independent crossings occurred. The earliest crossing occurred 130,000 years ago. The migrants landed in the Middle East and took a “beachcomber” route through Asia, hugging the coast toward India and then fanning out southward toward Burma, Malaysia, and Indonesia. A later crossing happened more recently, about sixty thousand years ago. These migrants moved north into Europe, where they encountered Neanderthals. Either route used the Yemeni peninsula as its hub. This is the true “melting pot” of the human genome.

  What is certain is that every perilous ocean-crossing left hardly any survivors—perhaps as few as six hundred men and women. Europeans, Asians, Australians, and Americans are the descendants of these drastic bottlenecks, and this corkscrew of history too has left its signature in our genomes. In a genetic sense, nearly all of us who emerged out of Africa, gasping for land and air, are even more closely yoked than previously imagined. We were on the same boat, brother.

  What does this tell us about race and genes? A great deal. First, it reminds us that the racial categorization of humans is an inherently limited proposition. Wallace Sayre, the political scientist, liked to quip that academic disputes are often the most vicious because the stakes are so overwhelmingly low. By similar logic, perhaps our increasingly shrill debates on race should begin with the recognition that the actual range of human genomic variation is strikingly low—lower than in many other species (lower, remember, than in chimpanzees). Given our rather brief tenure on earth as a species, we are much more alike than unlike each other. It is an inevitable consequence of the bloom of our youth that we haven’t even had time to taste the poisoned apple.

  Yet, even a young species possesses history. One of the most penetrating powers of genomics is its ability to organize even closely related genomes into classes and subclasses. If we go hunting for discriminatory features and clusters, then we will, indeed, find features and clusters to discriminate. Examined carefully, the variations in the human genome will cluster in geographic regions and continents, and along traditional boundaries of race. Every genome bears the mark of its ancestry. By studying the genetic characteristics of an individual you can pinpoint his or her origin to a certain continent, nationality, state, or even a tribe with remarkable accuracy. It is, to be sure, an apotheosis of small differences—but if this is what we mean by “race,” then the concept has not just survived the genomic era, it has been amplified by it.

  The problem with racial discrimination, though, is not the inference of a person’s race from their genetic characteristics. It is quite the opposite: it is the inference of a person’s characteristics from their race. The question is not, can you, given an individual’s skin color, hair texture, or language, infer something about their ancestry or origin. That is a question of biological systematics—of lineage, of taxonomy, of racial geography, of biological discrimination. Of course you can—and genomics has vastly refined that inference. You can scan any individual genome and infer rather deep insights about a person’s ancestry, or place of origin. But the vastly more controversial question is the converse: Given a racial identity—African or Asian, say—can you infer anything about an individual’s characteristics: not just skin or hair color, but more complex features, such as intelligence, habits, personality, and aptitude? Genes can certainly tell us about race, but can race tell us anything about genes?

  To answer this question, we need to measure how genetic variation is distributed across various racial categories. Is there more diversity within races or between races? Does knowing that someone is of African versus European descent, say, allow us to refine our understanding of their genetic traits, or their personal, physical, or intellectual attributes in a meaningful manner? Or is there so much variation within Africans and Europeans that intraracial diversity dominates the comparison, thereby making the category “African” or “European” moot?

  We now know precise and quantitative answers to these questions. A number of studies have tried to quantify the level of genetic diversity of the human genome. The most recent estimates suggest that the vast proportion of genetic diversity (85 to 90 percent) occurs within so-called races (i.e., within Asians or Africans) and only a minor proportion (7 percent) between racial groups (the geneticist Richard Lewontin had estimated a similar distribution as early as 1972). Some genes certainly vary sharply between racial or ethnic groups—sickle-cell anemia is an Afro-Caribbean and Indian disease, and Tay-Sachs disease has a much higher frequency in Ashkenazi Jews—but for the most part, the genetic diversity within any racial group dominates the diversity between racial groups—not marginally, but by an enormous amount. This degree of intraracial variability makes “race” a poor surrogate for nearly any feature: in a genetic sense, an African man from Nigeria is so “different” from another man from Namibia that it makes little sense to lump them into the same category.

  For race and genetics, then, the genome is a strictly one-way street. You can use genome to predict where X or Y came from. But, knowing where A or B came from, you can predict little about the person’s genome. Or: every genome carries a signature of an individual’s ancestry—but an individual’s racial ancestry predicts little about the person’s genome. You can sequence DNA from an African-American man and conclude that his ancestors came from Sierra Leone or Nigeria. But if you encounter a man whose great-grandparents came from Nigeria or Sierra Leone, you can say little about the features of this particular man. The geneticist goes home happy; the racist returns empty-handed.

  As Marcus Feldman and Richard Lewontin put it, “Racial assignment loses any general biological interest. For the human species, racial assignment of individuals does not carry any general implication about genetic differentiation.” In his monumental study on human genetics, migration, and race published in 1994, Luigi Cavalli-Sforza, the Stanford geneticist, described the problem of racial classification as a “futile exercise” driven by cultural arbitration rather than genetic differentiation. “The level at which we stop our classification is completely arbitrary. . . . We can identify ‘clusters’ of populations . . . [but] since every level of clustering would determine a different partition . . . there is no biological reason to prefer a particular one.” Cavalli-Sforza continued, “The evolutionary explanation is simple. There is great genetic variation in populations, even in small ones. This individual variation has accumulated over long periods, because most [genetic variations] antedate the separation into continents, and perhaps even the origin of the spec
ies, less than half a million years ago. . . . There has therefore been too little time for the accumulation of substantial divergence.”

  That extraordinary last statement was written to address the past: it is a measured scientific retort to Agassiz and Galton, to the American eugenicists of the nineteenth century, and to the Nazi geneticists of the twentieth. Genetics unleashed the specter of scientific racism in the nineteenth century. Genomics, thankfully, has stuffed it back into its bottle. Or, as Aibee, the African-American maid, tells Mae Mobley plainly in The Help, “So, we’s the same. Just a different color.”

  In 1994, the very year that Luigi Cavalli-Sforza published his comprehensive review of race and genetics, Americans were convulsing with anxiety around a very different kind of book about race and genes. Written by Richard Herrnstein, the behavioral psychologist, and Charles Murray, a political scientist, The Bell Curve was, as the Times described it, “a flame-throwing treatise on class, race and intelligence.” The Bell Curve offered a glimpse of how easily the language of genes and race can be distorted, and how potently those distortions can reverberate through a culture that is obsessed with heredity and race.

  As public flame-throwers go, Herrnstein was an old hand: his 1985 book, Crime and Human Nature, had ignited its own firestorm of controversy by claiming that ingrained characteristics, such as personality and temperament, were linked to criminal behavior. A decade later, The Bell Curve made an even more incendiary set of claims. Murray and Herrnstein proposed that intelligence was also largely ingrained—i.e., genetic—and that it was unequally segregated among races. Whites and Asians possessed higher IQs on average, and Africans and African-Americans possessed lower IQs. This difference in “intellectual capacity,” Murray and Herrnstein claimed, was largely responsible for the chronic underperformance of African-Americans in social and economic spheres. African-Americans were lagging behind in the United States not because of systematic flaws in our social contracts, but because of systematic flaws in their mental constructs.