Mitochondrial DNA is inherited from the mother alone, so all of it today had one female ancestor.

At first, most paleontologists clung to the much earlier date. But new fossil finds undermined the human status of Ramapithecus: it is now clear that Ra-mapithecus is actually Sivapithecus, a creature ancestral to orangutans and not to any of the African apes at all. Moreover, the age of some sivapithecine fossils was downgraded to only about six million years. By the early 1980s almost all paleontologists came to accept Sarich's more recent date for the separation of the human and ape lines. Those who continue to reject his methods have been reduced to arguing that Sarich arrived at the right answer purely by chance.

Two novel concepts emerged from the early comparisons of proteins from different species. One was the concept of inconsequential, or neutral, mutations. Molecular evolution appears to be dominated by such mutations, and they accumulate at surprisingly steady rates in surviving lineages. In other words, evolution at the gene level results mainly from the relentless accumulation of mutations that seem to be neither harmful nor beneficial. The second concept, molecular clocks, stemmed from the observation that rates of genetic change from point mutations (changes in individual DNA base pairs) were so steady over long periods that one could use them to time divergences from a common stock.

Mitochondrial Clue

WE COULD BEGIN to apply these methods to the reconstruction of later stages in human evolution only after 1980, when DNA restriction analysis made it possible to explore genetic differences with high resolution. Workers at Berkeley, including Wes Brown, Mark Stoneking and us, applied the technique to trace the maternal lineages of people sampled from around the world.

The DNA we studied resides in the mitochondria, cellular organelles that convert food into a form of energy the rest of the cell can use. Unlike the DNA of the nucleus, which forms bundles of long fibers, each consisting of a protein-coated double helix, the mitochondrial DNA comes in small, two-stranded rings. Whereas nuclear DNA encodes an estimated 100,000 genes—most of the information needed to make a human being—mitochondrial DNA encodes only 37. In this handful of genes, every one is essential: a single adverse mutation in any of them is known to cause some severe neurological diseases.

For the purpose of scientists studying when lineages diverged, mitochondrial DNA has two advantages over nuclear DNA. First, the sequences in mitochon-drial DNA that interest us accumulate mutations rapidly and steadily, according to empirical observations. Because many mutations do not alter the mitochondrion's function, they are effectively neutral, and natural selection does not eliminate them.

This mitochondrial DNA therefore behaves like a fast-ticking clock, which is essential for identifying recent genetic changes. Any two humans chosen randomly from anywhere on the planet are so alike in most of their DNA sequences that we can measure evolution in our species only by concentrating on the genes that mutate fastest. Genes controlling skeletal characters do not fall within this group.

Second, unlike nuclear DNA, mito-

chondrial DNA is inherited from the mother alone, unchanged except for chance mutations. The father's contribution ends up on the cutting-room floor, as it were. The nuclear genes, to which the father does contribute, descend in what we may call ordinary lineages, which are of course important to the transmission of physical characteristics. For our studies of modern human origins, however, we focus on the mito-chondrial, maternal lineages.

Maternal lineages are closest among siblings because their mitochondrial DNA has had only one generation in which to accumulate mutations. The degree of relatedness declines step by step as one moves along the pedigree, from first cousins descended from the maternal grandmother, to second cousins descended from a common maternal great-grandmother and so on. The farther back the genealogy goes, the larger the circle of maternal relatives becomes, until at last it embraces everyone alive.

Logically, then, all human mito-chondrial DNA must have had an ultimate common female ancestor. But it is easy to show she did not necessarily live in a small population or constitute the only woman of her generation. Imagine a static population that always contains 15 mothers. Every new generation must contain 15 daughters, but some mothers will not produce a daughter, whereas others will produce two or more. Because maternal lineages die out whenev

REBECCA L. CANN and ALLAN C. WILSON applied the tools of genetics to paleontology during many of their collaborations. Cann is professor of genetics and molecular biology at the John A. Burns School of Medicine of the University of Hawaii at Manoa. She received both her bachelor's degree in genetics and her Ph.D. in anthropology from the University of California, Berkeley. As a postdoctoral fellow, she worked at Berkeley with Wilson and at the University of California, San Francisco. Cann is using mitochondrial DNA to assay the genetic diversity of birds in the Hawaiian Islands. Until his death in 1991, Wilson was professor of biochemistry at Berkeley. A native of New Zealand, he received his doctorate from Berkeley. Wilson also worked at the Weizmann Institute of Science in Rehovot, Israel, at the University of Nairobi and at Harvard University.

er there is no daughter to carry it on, it is only a matter of time before all but one lineage disappears. In a stable population, the time for this fixation of the maternal lineage to occur is the length of a generation multiplied by twice the population size.

Eve in Africa

ONE MIGHT REFER to the lucky woman whose lineage survives as Eve. Bear in mind, however, that other women were living in Eve's generation and that Eve did not occupy a specially favored place in the breeding pattern. She is purely the beneficiary of chance. Moreover, if we were to reconstruct the ordinary lineages for the population, they would trace back to many of the men and women who lived at the same time as Eve. Population geneticists Daniel L. Hartl, now at Harvard University, and Andrew G. Clark, now at Cornell University, estimate that as many as 10,000 people could have lived then. The name "Eve" can therefore be misleading—she is not the ultimate source of all the ordinary lineages, as the biblical Eve was.

From mitochondrial DNA data, it is possible to define the maternal lineages of living individuals all the way back to a common ancestor. In theory, a great number of different genealogical trees could give rise to any set of genetic data. To recognize the one that is most probably correct, one must apply the parsimony principle, which requires that subjects be connected in the simplest possible way. The most efficient hypothetical tree must be tested by comparison with other data to see whether it is consistent with them. If the tree holds up, it is analyzed for evidence of the geographic history inherent in elements.

In 1988 Thomas D. Kocher of Berkeley (now at the University of New Hampshire) applied just such a parsimonious interpretation to the interrelatedness of the mitochondrial DNA of 14 humans from around the world. He determined that 13 branching points were the fewest that could account for the differences he found. Taking the geographic considerations into account, he then concluded that Africa was the ultimate human homeland: the global distribution of mi-tochondrial DNA types he saw could then be explained most easily as the result of no more than three migration events to other continents.

A crucial assumption in this analysis is that all the mitochondrial lineages evolve at the same rate. So when Kocher conducted his comparison of the human mitochondrial DNAs, he also included analogous sequences from four chimpanzees. If the human lineages had differed in the rate at which they accumulated mutations, then some of the 14 human sequences would be significantly closer or farther away from the chimpanzee sequences than others. In fact, all 14 human sequences are nearly equidistant from the chimpanzee sequences, which implies that the rates of change among humans are fairly uniform.

The chimpanzee data also illustrated how remarkably homogeneous humans are at the genetic level: chimpanzees commonly show as much as 10 times the genetic variation of humans. That fact alone suggests that all of modern humanity sprang from a relatively small stock of common ancestors.

Working at Berkeley with Stoneking, we expanded on Kocher's work by examining a larger genealogical tree made up of 182 distinct types of mitochondrial DNA from 241 individuals. The multiple occurrences of mitochondrial DNA types were always found among people from the same continent and usually in persons who lived within 100 miles of one another. Because the tree we constructed had two main branches, both of which led back to Africa, it, too, supported the hypothesis that Africa was the place of origin for modern humans.

One noteworthy point that jumps out of our study is that although geographic barriers do influence a population's mitochondrial DNA, people from a given continent do not generally all belong to the same maternal lineage. The New Guineans are typical in this respect. Their genetic diversity had been suspected from linguistic analyses of the remarkable variety of language families— usually classified as Papuan—spoken on this one island [see "The Austronesian Dispersal and the Origin of Languages," by Peter Bellwood; Scientific American, July 1991]. On our genealogical tree,

UNIVERSAL MATERNAL ANCESTOR can be found for all the members of any population. The example shown here traces the lineages of 15 females in a stable population. In each generation, some maternal lineages proliferate and others become extinct. Eventually, by chance, one maternal lineage (darkblue) replaces all the others.

UNIVERSAL MATERNAL ANCESTOR can be found for all the members of any population. The example shown here traces the lineages of 15 females in a stable population. In each generation, some maternal lineages proliferate and others become extinct. Eventually, by chance, one maternal lineage (darkblue) replaces all the others.

Huge levels of gene flow between early continents—very unlikely—would have been needed for multiregionalism.

New Guineans showed up on several different branches, which proved that the common female ancestor of all New Guineans was not someone in New Guinea. The population of New Guinea must have been founded by many mothers whose maternal lineages were most closely related to those in Asia.

That finding is what one would expect if the African origin hypothesis were true: as people walked east out of Africa, they would have passed through Asia. Travel was probably slow, and during the time it took to reach New Guinea, mutations accumulated both in the lineages that stayed in Asia and in those that moved on.

Thus, people who are apparently related by membership in a common geographic race need not be very closely related in their mitochondrial DNA. Mi-

tochondrially speaking, races are not like biological species. We propose that the anatomical characteristics uniting New Guineans were not inherited from the first settlers. They evolved after people colonized the island, chiefly as the result of mutations in nuclear genes spread by sex and recombination throughout New Guinea. Similarly, the light skin color of many whites is probably a late development that occurred in Europe after that continent was colonized by Africans.

During the early 1980s, when we were constructing our genealogical tree, we had to rely on black Americans as substitutes for Africans, whose mito-chondrial DNA was difficult to obtain in the required quantities. Fortunately, the development of a technique called the polymerase chain reaction has eliminat-

ed that constraint. The reaction makes it possible to duplicate DNA sequences easily, ad infinitum; a small starting sample of DNA can expand into an endless supply.

The polymerase chain reaction enabled Linda Vigilant of Pennsylvania State University to redo our study using mitochondrial DNA data from 120 Africans, representing six diverse parts of the sub-Saharan region. Vigilant traced a genealogical tree whose 14 deepest branches lead exclusively to Africans and whose 15th branch leads to both Africans and non-Africans. The non-Africans lie on shallow secondary branches stemming from the 15th branch. Considering the number of African and non-African mitochondrial DNAs surveyed, the probability that the 14 deepest branches would be exclusively African is one in 10,000 for a tree with this branching order.

Satoshi Horai and Kenji Hayasaka of the National Institute of Genetics in Mishima, Japan, analogously surveyed population samples that included many more Asians and individuals from fewer parts of Africa; they, too, found that the mitochondrial lineages led back to Africa. We estimate the odds of their arriving at that conclusion accidentally were only four in 100. Although these statistical evaluations are not strong or rigorous tests, they do make it seem likely that the theory of an African origin for human mitochondrial DNA is now fairly secure.

200,000 Years or Less

BECAUSE OUR COMPARISONS with the chimpanzee data showed that the human mitochondrial DNA clock has ticked steadily for millions of years, we knew it should be possible to calculate when the common mother of humanity lived. We assumed that the human and chimpanzee lineages diverged five mil-

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