Molecular Anthropology

Anthropology is the study of the origin and development of the human species. Molecular anthropology uses the tools and techniques of molecular genetics to answer anthropological questions, especially those concerning the origins and spread of humans across the globe. These questions mainly fall under the heading of physical or biological anthropology, as opposed to cultural anthropology, which studies social relationships, rituals, and other aspects of culture.

Tracing Human Origins through Genetic Data

Molecular anthropology attempts to answer such questions as whether humans are more genetically similar to chimpanzees than to gorillas; in what region or regions modern humans first developed; what the patterns are of migration and mixture of early human populations; and whether Neandertals were a different species, and whether they died out or mixed in with modern humans. Molecular anthropology is perhaps best known for the studies that surround the discovery of "mitochondrial Eve" (discussed below), although the meaning of that discovery is often misunderstood.

Two major approaches are used in addressing these questions, both of which involve analyzing DNA. The first and most common approach is to compare the DNA of groups of living organisms, for example, comparing humans to humans or humans to primates. The second approach relies on isolating and analyzing DNA from an ancient source, and comparing it to other ancient DNA or to modern DNA. In both cases, the number of differences between the DNA sequences of the two groups are determined, and these are used to draw conclusions about the relatedness of the two groups, or the time since they diverged from a common ancestor, or both.

The results of molecular anthropological studies are rarely used alone. Instead, the data are combined with information from fossils, archaeological excavations, linguistics, and other sources. Sometimes the data from these different sources conflict, however, and much of the controversy in anthropology centers around how much weight to give each when this occurs.

Advantages of DNA Comparisons

The essential postulate on which molecular anthropology is based is that closer genetic similarity indicates a more recent common ancestry. All organisms are believed to have evolved from a single ancestor. As different life forms evolved, their DNA began to diverge through the processes of mutation, natural selection, and genetic drift. Even within the same species, populations that do not interbreed will accumulate genetic differences, which increase over time. The number of these differences is proportional to the amount of time since the two groups diverged.

There are several advantages to comparing DNA data instead of external physical characteristics (collectively called the phenotype). Environmental factors can shape the phenotype to make two individuals with the same genetic makeup look different. For instance, nutrition has a profound effect on height, and if we used average height to classify humans, we might mistakenly conclude that medieval humans represented a different sub-species because they were significantly shorter than modern humans. DNA comparisons, on the other hand, would show no significant difference between these groups.

Another advantage is that DNA sequence differences can be easily quantified—two base changes in a gene are more different than one. Despite being random events, mutations occur at a fairly steady rate, constituting a "molecular clock," and so the number of differences can be use to estimate the time since the two organisms shared a common ancestor.

Finally, since all organisms contain DNA, the sequences of any two organisms can be compared. The same techniques used in molecular anthropology can also be applied to evolutionary questions in other species, to determine the evolutionary relations between different animal species, for instance, or even between bacteria and humans.

Caveats About Sequence Comparisons

On the other hand, the simplicity and power of sequence comparisons can lead too easily to an oversimplified interpretation of results, and to conclusions that may sound more significant than they are. A prime example is the often-repeated statement that humans and chimpanzees share 98 percent of their DNA.

It may be true that 98 out of 100 bases are the same in the two genomes, but what is the significance of this fact? It does not mean that 98 percent of our genes are identical. In fact, almost all of them differ slightly, some dramatically. It also does not tell us whether the significant differences between humans and chimps arise from a few very different genes, or many slightly different ones. Moreover, there are significant differences in genome structure not accounted for by the sequence comparison. For instance, humans have forty-six chromosomes, whereas chimpanzees have forty-eight; they have about 10 percent more DNA than humans do; and humans have more copies of a certain kind of transposable genetic element than they do.

Most importantly, the sequence similarity certainly does not tell us that humans "are" 98 percent chimpanzee—we are two entirely different species, as is obvious from differences in anatomy and behavior. If the profound differences between humans and chimps are not reflected in the sequence data, it may be that this simple tabulation of difference does not adequately summarize the ways in which DNA can cause two organisms to differ.

The 98 percent figure, therefore, may be used to say that chimps and humans are closely related, and are more closely related to each other than either is to an organism with a greater number of sequence differences, such as the orangutan. However, it may not be used to draw conclusions about the similarity of humans and chimps as organisms.

Types of DNA Comparisons

The human genome is much too large to sequence all of it to make comparisons, using current technology. Instead, much smaller portions of it are used. One strategy is to compare gene sequences, such as the sequence for hemoglobin. A potential problem with this is that most mutations in such useful genes are harmful, and so the few harmless mutations they accumulate may be similar between two individuals, despite a long evolutionary separation. Nonetheless, gene comparisons are useful for distantly related species, such as humans and yeast.

An alternative is to look at noncoding regions of DNA. These include microsatellite DNA sequences, a type of repetitive DNA element found throughout the genome. Because these sequences do not code for protein, most mutations in them do not affect the viability of the organism in which they occur. Thus they accumulate mutations more quickly. Another option is single nucleotide polymorphisms. These are sequences which differ among individuals or groups by a single nucleotide. There are millions of such sequences in the genome. Because there are so many different forms, these noncoding sequences are especially useful for determining kinship among closely related individuals, such as members of a tribe or extended family.

One potential problem with sequence comparisons is back mutation, in which a base mutates to another, and then reverts to the original (for example, C → T → C). When this occurs, two sequences may appear to be more closely related (less separated in time) than they really are, since the intervening mutation (the change from C to T, in this case) may not be apparent. Because of back mutation, the observed number of differences between sequences represents the minimum actual difference. Correction factors can be applied to estimate the true difference.

Another potential problem with any sequence on a chromosome, whether or not that sequence codes for a protein, is that most chromosomes do not remain intact during meiosis . This is because crossing over occurs, in which homologous chromosomes recombine (exchange segments). After a few generations, it becomes very difficult to track individual sequences and compare them with any confidence to similar sequences in another person. To avoid this problem, molecular anthropologists focus on two sources of DNA that do not recombine: the Y chromosome and mitochondrial DNA.

The Y Chromosome

The Y chromosome, which determines male sex, does not undergo recombination along most of its length. Instead, it passes intact from father to son. A man's Y chromosome, therefore, is a more-or-less exact copy of the one possessed by his father, grandfather, great-grandfather, and so on back through time. Like any other DNA segment, it may mutate, and any changes it accumulates are faithfully passed along as well. Two brothers are likely to have exactly the same Y chromosome sequence. Two men whose last common male ancestor was ten generations ago, however, are likely to have slightly different sequences. Comparison of the sequences of two Y chromosomes, therefore, can show how closely related two males are.

Y chromosome analysis has been used to track migration of human populations, and to study the relatedness of modern populations. For instance, Jews and Palestinian Arabs derive from a common ancestral population that lived in the Middle East about 4,000 years ago. Recent studies have linked the ancestors of American Indians to several small populations in Siberia, confirming the predominantly Asian origin of American Indians and refining the understanding of their migration history. Many other similar studies have been performed, providing an increasingly clear (and complex) picture of human migration and mixture.

Mitochondrial DNA and the Origin of Modern Humans

Mitochondria are energy-harvesting organelles in the cell. They are inherited only from the mother, and so track maternal inheritance in the same way that the Y chromosome tracks paternal inheritance. Like microsatellite DNA, mitochondrial DNA accumulates mutations faster than chromosomal coding DNA.

One of the earliest and most famous mitochondrial studies was used to address a central question in anthropology: Where and how did modern humans originate?

The Homo genus itself is universally believed to have originated in Africa. Groups of Homo erectus are known to have migrated out of Africa, populating Europe and Asia between one and two million years ago. H. erectus gradually changed in character, so that by about half a million years ago, it had taken on some more modern characteristics. Anthropologists call these groups "archaic" modern humans. They include the Neandertals, who lived in Europe and the Middle East from 150,000 to 28,000 years ago. Did modern humans evolve from these older populations in several different regions simultaneously? Or did they arise from a small group in Africa, and spread out from there? If so, did they mix with less advanced local populations (such as Neandertals), or replace them entirely?

The scientists who performed the mitochondrial DNA study (Rebecca Cann, Mark Stoneking, and Allan Wilson) reasoned that populations that had been in one place for only a short period of time would show very little variation in their mitochondrial DNA, since they all shared a relatively recent common ancestor. This would be the case in a modern human population if it had only recently migrated into the area in which it is found. (Such relative genetic homogeneity in newly formed populations is known as the founder effect.) In contrast, populations that have remained in place for long periods have much more ancient common ancestors, and therefore have more mitochondrial DNA variations.

To perform their analysis, the scientists collected samples from different ethnic groups from all over the world. They found that the populations with the greatest amount of sequence variation were in sub-Saharan Africa, indicating these were the groups with the most ancient ancestry. All other groups had much less variation, indicating more recent arrivals of those groups in those regions. Cann, Stoneking, and Wilson went on to estimate the date at which all these groups had their most recent common ancestor. Using a figure of 2 to 4 percent sequence divergence per million years, they estimated that the most recent common ancestor lived approximately 200,000 years ago.

The simplest explanation, they argued, was that ancestors of the non-African Homo sapiens migrated out of Africa about 200,000 years ago to populate other regions, over time replacing the nonmodern humans (H. erectus, Neandertals, and possibly others) already living in these regions. They argued that the relatively short time since the divergence of all modern humans was too brief to support the alternative hypothesis, that each local group of archaic humans had independently evolved modern traits, a model called multiregional evolution.

The conclusions drawn in this study are still controversial. Numerous other studies have been done since, and the data have been subjected to multiple different analyses. Some studies suggest differing dates for the most recent common ancestor (ranging from 100,000 to 400,000 years ago), and others suggest that an exclusive African origin is not the only possible interpretation of the data.

It is important to keep in mind that the vast number of comparisons that must be made in such studies require computer programs, not only to make the comparisons, but to draw from them the simplest "family tree" that fits. Much of the controversy surrounds the assumptions that must be built into these programs in order to generate results. The mutation rates by which events are timed (the "molecular clock") are also not known with precision, leading to further uncertainties about the exact timing of migrations.

Mitochondrial Eve

In their study, Cann, Stoneking, and Wilson pointed out that the patterns of mitochondrial variations they saw suggested that all the mitochondria of all living groups could be traced back to a single woman who lived in Africa approximately 200,000 years ago. Many people at the time of the original study and since have misinterpreted the results to claim there was a single female ancestor for all modern humans, dubbed "Eve." It is true the study showed that the mitochondrial DNA in all living humans probably derives from this single woman. However, our nuclear DNA certainly does not derive exclusively (perhaps even at all) from this woman, and the thirty thousand or more genes in our nuclear DNA are far, far more important in determining our characteristics than the thirty-seven mitochondrial genes. Because of recombination, our nuclear DNA cannot be traced back to any single person. Rather, it is an amalgam of countless ancestors through time.

Mitochondrial Eve was also not the first modern human woman, nor the only woman in existence at the time she lived. She was not even the only woman in her local population; it is estimated that Eve was one of about 10,000 people in her population. There was really nothing particularly special about her, except that, by chance, the descendants of her mitochondria happen to have ended up in the cells of every living human. Even this, which sounds remarkable, is pretty much what we should expect from small populations.

To understand why, consider four couples, each of which has two children. Remember that mitochondria are passed from the mother to each child. One couple has two boys. Each boy inherits the mother's mitochondria, but neither passes them on to his children. The mother's mitochondrial type thus becomes extinct in one generation. Two of the couples have a boy and a girl, while the fourth has two girls. These four daughters go on to have children of their own, each with the same distribution according to sex. Whenever a family has only boys, a mitochondrial type becomes extinct. Any time a family has only girls, the mitochondrial type handed down from the mother becomes more common in the next generation. In a small population, over time, it is highly likely that one type will become most prevalent, ultimately becoming the one type found in all the members of the population. Looking back, we would give the name "Eve" to the original mother of that line of mitochondrial genetic inheritance.

A similar phenomenon occurs with the Y chromosome, for exactly the same reasons: Any family with only girls extinguishes that Y chromosome type. The "Y chromosome Adam" lived 60,000 to 150,000 years ago. There is no reason to expect that "Y chromosome Adam" would know "mitochondrial Eve"; indeed, even without the dates to make it impossible, it would be a remarkable coincidence if they had.

Neandertal DNA

DNA can be extracted from some archaeological samples, allowing direct sequencing and comparison with modern DNA. This has so far been possible with specimens up to about 40,000 years old (the dating of such samples is often inexact). DNA is isolated, purified, amplified with the polymerase chain reaction, and sequenced. By this technique, DNA from extinct animals such as the woolly mammoth has been obtained, but not dinosaur DNA, which is millions of years old. The DNA that can be isolated is typically highly fragmented and incomplete, and unsuitable for cloning the whole organism. One application is to analyze the DNA from plant and animal material at camp sites to determine the diet of early humans.

DNA can also be extracted from ancient human remains. As of summer 2002, mitochondrial DNA from two Neandertal skeletons had been extracted, sequenced, and compared. The first was from Germany, and was approximately 35,000 to 70,000 years old. A 378-base pair sequence was determined, and compared to almost one thousand different modern humans. On average, it differed at twenty-seven locations, while modern humans differed among each other at an average of only eight locations. There was some overlap, however, with the least number of differences between Neandertals and modern humans being twenty-two, and the greatest difference noted between modern humans being twenty-three.

The second skeleton was from Russia, and was 29,000 years old. A 345-base pair sequence was determined. It differed at twenty-three locations from a standard modern human sequence, but at only twelve locations compared to the German Neandertal DNA.

Keeping in mind that only two Neandertal sequences have been studied so far, some tentative conclusions have been offered from these data. The amount of difference between the two Neandertal sequences is similar to the amount found between randomly selected modern humans, suggesting that these two specimens, despite being separated by thousands of years, were indeed part of the same lineage.

The amount of difference between the Neandertal skeletal DNA and modern humans suggests that Neandertals were genetically distinctly different from modern humans in their mitochondrial DNA. Were they different enough to constitute a separate species? That is much less clear, and is a source of disagreement among anthropologists. The difference is much less than that between modern humans and chimpanzees, for instance, which suggests that they were not separate species, but it is greater than the differences among subspecies of chimpanzees, which suggests that perhaps they were. Scientists have not been able to compare Neandertal sequences to sequences from anatomically modern humans living at the same time as the Neandertals. It may be that those sequences would be more similar. At present, the relationship of Neandertals to modern humans has still not been conclusively determined.

Conclusion

Using the tools of molecular genetics, DNA sequences can be compared among groups to test hypotheses about the evolutionary relatedness of organisms, and about the time that has elapsed since divergence. Molecular anthropology has made major contributions to understanding the migration and mixture patterns of human groups. It has also provided significant new insights into the rise and spread of modern humans and their relation to earlier human groups. As more data becomes available and better models are devised for their interpretation, the results are likely to become less provisional and more certain.

see also Inheritance, Extranuclear; Founder Effect; Mitochondrial Genome; Mutation Rate; Polymorphisms; Population Bottleneck; Repetitive DNA Elements; Sequencing DNA; Y Chromosome.

Richard Robinson

Bibliography

Avise, John C. Molecular Markers, Natural History, and Evolution. New York: Chapman and Hall, 1994.

Hammer, M. F., et al. "Jewish and Middle Eastern Non-Jewish Populations Share aCommon Pool of Y Chromosome Biallelic Haplotypes." Proceedings of the National Academy of Sciences 97, no. 12 (2000): 6769-6774.

Marks, Jonathan. What It Means to Be 98% Chimpanzee: Apes, People, and Their Genes. Berkeley, CA: University of California Press, 2002.

Relethford, John H. Genetics and the Search for Human Origins. New York: Wiley-Liss, 2001.

Vigilant, L., et al. "African Populations and the Evolution of Human MitochondrialDNA." Science 253 (1991): 1503-1507

Internet Resource

Y Chromosome Links. <http://john.hynes.net/y.html>.

Analysis of Y chromosome microsatellite sequences was used to show that Thomas Jefferson was an ancestor of some of the male descendants of Sally Hemings, a slave owned by Jefferson.