The study of primate phylogeny and human evolution through the genetic information in the deoxyribonucleic acid (DNA) of genomes and in the proteins that genes encode. The first studies in molecular anthropology used immunological and biochemical methods to obtain information from proteins on the degrees of genetic similarity of humans and other primates. These results not only placed chimpanzees and gorillas closest to humans rather than to orangutans but also indicated that the very close kinship between chimpanzees and gorillas was not any closer than the relation of each to humans. Subsequent studies that extracted genetic information directly from DNA extended this original finding. Indeed, the accumulating comparative DNA sequence data provide mounting evidence that the closest genetic kinship is between chimpanzees and humans rather than chimpanzees and gorillas.
The results gathered in DNA studies of primate phylogeny challenge the traditional anthropological view that humans are very different from all other animals. DNA results show that, genetically, humans are only slightly remodeled apes. Humans share with their closest relatives, the chimpanzees and bonobos (pygmy chimpanzees), more than 98.3% identity in typical noncoding DNA and probably about 99.5% identity in the active coding sequences of functional nuclear genes. Humans share about 98.0% identity in nuclear genomic DNA with gorillas, 96.5% identity with orangutans, and 95.0% identity with the most distant ape relatives, the gibbons and siamangs. Apes and humans share with the other branch of catarrhines, the Old World monkeys, about 92% identity in nuclear genomic DNA, and with the platyrrhines, the New World monkeys, about 87% identity. Even with nonanthropoid primates, the tarsiers and strepsirhines (lemurs and loriforms, such as bushbabies), the anthropoids (platyrrhines and catarrhines) share a DNA identity in the range of 76–71%. See alsoDeoxyribonucleic acid (DNA).
Traditional primate classifications use the vague concept of grades of evolutionary advancement to place the smaller-brained primates in the suborder Prosimii (the primitive grade) and the larger-brained primates in the suborder Anthropoidea (the advanced grade). Moreover, on viewing humans as the most advanced primates, traditional primate classifications have humans as the sole living members of family Hominidae, while the great apes of Africa (chimpanzees, bonobos, gorillas) and Asia (orangutans) are members of subfamily Ponginae of family Pongidae. In contrast, a strictly objective view based on molecular evidence, but also congruent morphological evidence from both living and fossil primates, not only places apes with humans within the family Hominidae but also within this family places chimpanzees and bonobos with humans in the genus Homo. See alsoApes; Fossil apes; Fossil humans; Fossil primates; Mammalia.
After the divergence of Homo (Homo) from Homo (Pan) paniscus (bonobos, or pygmy chimpanzees), humankind's emergence was marked by mutations (such as DNA sequence changes) that spread to fixation in the ancestors of all modern humans. These mutations are the human-specific factors which distinguish the human species genetically from all other species. Ongoing evolution involves mutations that have not spread to fixation, either because they occurred too recently or because natural selection has maintained a polymorphic state. These mutations occur at frequencies that occasionally differ from one human group to another. They account for the genetic diversity found in the human species. Extensive comparative data now exist on the genetic diversity due to mitochondrial genetic variants (which arise from mutations in the DNA carried by mitochondria). The species-wide distribution of mitochondrial haplotypes in present-day human populations compared to the distribution in chimpanzees reveals that humans show less DNA diversity than chimpanzees. Human populations in different ethnic groups (European Norwegians and South African hottentots) and even within the same group share 85–90% of the total species diversity. The human genetic diversity due to mutations in nuclear DNA (the DNA carried by the chromosomes of cells) also shows this same pattern in which most of the variation within the human species as a whole is contained within single populations. These findings argue that all living humans are biologically not only members of the same species but also the same subspecies and even the same race, the human race. A further inference from the data on mitochondrial genetic diversity is that the birth of the human race took place in Africa about 200,000 years ago. See alsoMitochondria.
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.
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 chromosomesrecombine (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.
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
Molecular anthropology is a field of anthropology in which molecular analysis is used to determine evolutionary links between peoples, ancient and modern populations, as well as between contemporary species. Generally, comparisons are made between sequence, either DNA or protein sequence, however early studies used comparative serology.
By examining DNA sequences in different populations, scientist can determine the closeness relationships between populations (or within populations). Certain similarities in genetic makeup let molecular anthropologists determine whether or not different groups of people belong to the same haplogroup, and thus if they share a common geographical origin. This is significant because it allows anthropologists to trace patterns of migration and settlement, which gives helpful insight as to how contemporary populations have formed and progressed over time.[1]
Molecular anthropology has been extremely useful in establishing the evolutionary tree of humans and other primates, including closely related species like chimps and gorillas. While there are clearly many morphological similarities between humans and chimpanzees, for example, not many would have guessed that the two have roughly 98 percent of their DNA in common.[citation needed] Such information is useful in searching for common ancestors and coming to a better understanding of how humans evolved.
Image of mitochondrion. There many mitochondria within a cell, and DNA in them replicate independently of the chromosomes in the nucleus.
There are two continuous linkage groups in human that are carried by a single sex. The first is the Y-chromosome, which is passed from father to son. Rarely do anatomical females carry a Y chromosome as a result of genetic defect. The other linkage group is the mitochondrial DNA (mtDNA). MtDNA can only be passed to the next generation by females but only under highly exceptional circumstances is mtDNA passed through males. The non-recombinant portion of the Y chromosome and the mtDNA, under normal circumstances, do not undergo productive recombination. Part of Y chromosome can undergo recombination with X chromosome and within ape history the boundary has changed. Such recombinant changes in the non-recombinant region of Y are extremely rare.[citation needed]
Mitochondrial DNA
Illustration showing mitochondrial DNA, the control region (D-loop, hypervariable regions 1 and II are located on left and right side at the top, respectively)
Mitochondrial DNA became an area of research in phylogenetics in the late 1970s. Unlike genomic DNA is offered advantages in that it did not undergo recombination. The process of recombination, if frequent enough corrupts the ability to create parsimonious trees because stretches of amino acid subsititions (SNPs). When looking between distantly related species, recombination is less of a problem since recombination between branches from common ancestors is prevented after true speciation occurs. When examining closely related species, or branching within species recombination creates a large number of 'irrelevant SNPs' for cladistic analysis. MtDNA, through the process of organelle division, become clonal over time, very little, too often none, of that paternal mtDNA is passed. While recombination may occur in mtDNA, there is little risk that it will be passed to the next generation. As a result mtDNA become clonal copies of each other, except when a new mutation arises. As a result mtDNA does not have pitfalls of autosomal loci when studied in interbreeding groups. Another advantage of mtDNA is that the hyper-variable regions evolve very quickly, this exhibits that certain regions of mitochondrial DNA approach neutrality. This allowed the use of mitochondrial DNA to determine that the relative age of the human population was small having gone through a recent constriction at about 150,000 years ago (see Sources of error). Mitochondrial DNA has also been used to verify the proximity of chimpanzees to humans relative to gorilla, and to verify the relationship of these 3 species relative to orangutan.
A population bottleneck, as illustrated was detected by intrahuman mtDNA phylogenetic studies, the length of the bottleneck itself is indeterminant per mtDNA.
More recently the mtDNA genome has been used to estimate branching patterns in peoples around the world, such as when the new world was settled and how. The problem with these studies have been that they rely heavily on mutations in the coding region. Researchers have increasingly discovered that as humans moved from Africas south-eastern regions, that more mutations accumulated in the coding region than expected, and in passage to the new world some groups are believe to have passed from the Asian tropics to Siberia to an ancient land region called Beringia and quickly migrating to south America. Many of the mtDNA have far more mutations and at rarely mutated coding sites relative to expectations of neutral mutations.
Mitochondrial DNA offers another advantage over autosomal DNA. There are generally 2 to 4 copies of each chromosome in each cell (1 to 2 from each parent chromosome). For mtDNA there can be dozens to hundreds in each cell. This increases the amount of each mtDNA loci by at least a magnitude. For ancient DNA, in which the DNA is highly degraded, the number of copies of DNA is helpful in extending and bridging short fragments together, and decreases the amount of bone extracted from highly valuable fossil/ancient remains. Unlike Y chromosome both male and female remains carry mtDNA in roughly equal quantities.
Y chromosome is found in the nucleus of normal cells (Nuclear DNA). Unlike mtDNA, it has mutations in the non-recombinant portion (NRY) of the chromosome spaced widely apart, so far apart that finding the mutations on new Y chromosomes is labor intensive relative to mtDNA. Many studies rely on tandem repeats; however, tandem repeat can expand and retract rapidly and in some predictable patterns. Y chromosome only tracks male lines, and is not found in females; whereas mtDNA can be traced in males even though they fail to pass mtDNA. In addition it has been estimated that effective male populations in the prehistoric period were typically 2 females per male, and recent studies show that cultural hegemony plays a large role in the passage of Y. This has created disconcordance between the time to most recent common ancestor of males and females. The estimates for Y TMRCA range from 1/4th to less than 1/2 that of mtDNA TMRCA. It is unclear whether this is due to high male-to-female ratios in the past coupled with repeat migrations from Africa, as a result of mutational rate change, or some have even proposed that females of the LCA between chimps and humans continued to pass DNA millions after males ceased to pass DNA. At present the best evidence suggests that in migration the male to female ratio in humans may have declined causing a trimming of Y diversity on multiple occasions within and outside of Africa.
For short range molecular phylogenetics and molecular clocking Y chromosome is highly affective and creates a second perspective. One argument that arose was that the Maori by mtDNA appear to have migrated from Eastern China or Taiwan, by Y chromosome from Papua New Guinea region. When HLA haplotypes were used to evaluate the two hypothesis it was uncovered that both were right, that the Maori were an admixed population. Such admixtures appear to be common in the human population and thus the use of a single haploid loci can give a biased perspective.
X-linked Studies
The X-chromosome is also a form of nuclear DNA. Since it is found as 1 copy in males and 2 non-identical chromsomes in females it has a ploidy of 1.5. However, in humans the effective ploidy is somewhat higher, ~1.7, as females in the breeding population have tended to outnumber males by 2:1 during a large portion of human prehistory. Like mtDNA, X-linked DNA tends to over emphasize female population history much more than male. There have been several studies of loci on X chromosome, in total 20 sites have been examined. These include PDHA1, PDHA1, Xq21.3, Xq13.3, Zfx, Fix, Il2rg, Plp, Gk, Ids, Alas2, Rrm2p4, AmeIX, Tnfsf5, Licam, and Msn. The time to most recent common ancestor(TMRCA) ranges from fixed to ~1.8 million years, with a median around 700ky. These studies roughly plot to the expected fixation distribution of alleles, given linkage disequilibrium between adjacent sites. For some alleles the point of origin is elusive, for others, the point of origin points toward Sub-saharan Africa. There are some distinctions within SSA that suggest a smaller region, but there is not adequate enough sample size and coverage to define a place of most recent common ancestor. The TMRCA is consistent with and extends the bottleneck implied by mtDNA, confidently to about 500,000 years.
Autosomal Loci
Diagram of human karyotype
Rate variation
Ancient DNA sequencing
Since Krings Neandertal mtDNA have been sequenced, and the sequence similarity indicates an equally recent origin from a small population on the Neanderthal branch of late hominids. MCR1 gene has also been sequenced but the results are controversial, with one study claiming that contamination issues cannot be resolved from human Neandertal similarities. Critically however no DNA sequence has been obtained from Homo erectus, Homo floriensis, or any of the other late hominids. Some of the ancient sequences obtained have highly probable errors, and proper control to avoid contamination.
Comparison of differences between human and Neanderthal mtDNA
Causes of errors
The molecular phylogenetics is based on quantitating substitutions and then comparing sequence with other species, there are several points in the process which create errors. The first and greatest challenge is finding "anchors" that allow the research to calibrate the system. In this example, there are 10 mutations between chimp and humans, but the researcher has no known fossils that are agreeably ancestral to both but not ancestral to the next species in the tree, gorilla. However, there are fossils believed to be ancestral to Orangutans and Humans, from about 14 million years ago. So that the researcher can use Orangutan and Human comparison and comes up with a difference of 24. Using this he can estimate (24/(14*2, the "2" is for the length of the branch to Human (14my) and the branch to Orangutan (14 my) from their last common ancestor (LCA). The mutation rate at 0.857 for a stretch of sequence. Mutation rates are given, however, as rate per nucleotide(nt)-site, so if the sequence were say 100 nt in length that rate would be 0.00857/nt per million years. Ten mutations*100nt/(0.00857*2) = 5.8 million years.
The problem of calibration
There are several problems not seen in the above. First, mutations occur as random events. Second, the chance that any site in the genome varies is different from the next site, a very good example is the codons for amino acids, the first two nt in a codon may mutate at 1 per billion years, but the third nt may mutate 1 per million years. Unless scientist study the sequence of a great many animals, particularly those close to the branch being examined, they generally do not know what the rate of mutation for a given site. Mutations do occur at 1st and 2nd positions of codons, but in most cases these mutations are under negative selection and so are removed from the population over small periods of time. In defining the rate of evolution in the anchor one has the problem that random mutation creates. For example a rate of .005 or .010 can also explain 24 mutations according to the binomial probability distribution. Some of the mutations that did occur between the two have reverted, hiding an initially higher rate. Selection may play into this, a rare mutation may be selective at point X in time, but later climate may change or the species migrates and it is not longer selective, and pressure exerted on new mutations that revert the change, and sometimes the reversion of a nt can occur, the greater the distance between two species the more likely this is going to occur. In addition, from that ancestral species both species may randomly mutate a site to the same nucleotide. Many times this can be resolved by obtaining DNA samples from species in the branches, creating a parsimonious tree in which the order of mutation can be deduced, creating branch-length diagram. This diagram will then produce a more accurate estimate of mutations between two species. Statistically one can assign variance based on the problem of randomnicity, back mutations, and parallel mutations (homoplasies) in creating an error range.
There is another problem in calibration however that has defied statistical analysis. There is a true/false designation of a fossil to a least common ancestor. In reality the odds of having the least common ancestor of two extant species as an anchor is low, often that fossil already lies in one branch (underestimating the age), lies in a third branch (underestimating the age) or in the case of being within the LCA species, may have been millions of years older than the branch. To date the only way to assess this variance is to apply molecular phylogenetics on species claimed to be branch points. This only, however identifies the 'outlying' anchor points. And since it is more likely the more abundant fossils are younger than the branch point the outlying fossil may simply be a rare older representative. These unknowns create uncertainty that is difficult to quantitate, and often not attempted.
Recent papers have been able to estimate, roughly, variance. The general trend as new fossils are discovered, is that the older fossils underestimated the age of the branch point. In addition to this dating of fossils has had a history of errors and there have been many revised datings. The age assigned by researchers to some major branch points have almost doubled in age over the last 30 years. An excellent example of this is the debate over LM3 (Mungo lake 3) in Australia. Originally it was dated to around 30 ky by carbon dating, carbon dating has problems, however, for sampled over 20ky in age, and severe problems for samples around 30ky in age. Another study looked at the fossil and estimated the age to be 62 ky in age.
At the point one has an estimation of mutation rate, given the above there must be two sources of variance that need to be cross-multiplied to generate an overall variance. This is infrequently done in the literature.
Problems in estimating TMRCA
Time to most recent common ancestor (TMRCA) combines the errors in calibration with errors in determining the age of a local branch.
History of Molecular Anthropology
The protein era
Structure of human hemoglobin. Hemoglobins from dozens of animals and even plants were sequenced in the 1960s and early 1970s
With DNA newly discovered as the genetic material, in the early 1960s protein sequencing was beginning to take off.[2] Protein sequencing began on cytochrome C and Hemoglobin. Gerhard Braunitzer sequenced hemoglobin and myoglobin, in total more than 100s of sequences from wide ranging species were done. In 1967 A.C. Wilson began to promote the idea of a "molecular clock". By 1969 molecular clocking was applied to anthropoid evolution and V. Sarich and A.C. Wilson found that albumin and hemoglobin has comparable rates of evolution, indicating chimps and humans split about 4 to 5 million years ago.[3] In 1970, Louis Leakey confronted this conclusion with arguing for improper calibration of molecular clocks.[4] By 1975 protein sequencing and comparative serology combined were used to propose that humans closest living relative (as a species) was the chimpanzee.[5] In hindsight, the last common ancestor (LCA) from humans and chimps appears to older than the Sarich and Wilson estimate, but not as old as Leakey claimed , either. However, Leakey was correct in the divergence of old and new world monkeys, the value Sarich and wilson used was a significant underestimate. This error in prediction capability highlights a common theme. (See Causes of Error)
The DNA era
Restriction fragment length polymorphisms studies the cutting of mtDNA into fragements, Later the focus of PCR would be on the D 'contol'-loop, at the top of the circle
RLFP and DNA hybridization
In 1979. W.M.Brown and Wilson began looking at the evolution of mitochodrial DNA in animals, and found they were evolving rapidly.[6] The technique they used was restriction fragment length polymorphism(RFLP) which was more affordable at the time compared to sequencing. In 1980, W.M. Brown, looking at the relative variation between human and other species, recognizes there was a recent constriction (180,000 years ago) in the human population.[7] A year later Brown and Wilson were looking at RFLP fragments and determined the human population expanded more recently than other ape populations.[8]. In 1984 the first DNA sequence from an extinct animal was done.[9] Sibley and Ahlquist apply DNA-DNA hybridization technology to anthropoid phylogeny, and see pan/human split closer than gorilla/pan or gorilla/human split, a highly controversial claim.[10][11] However, in 1987 they were able to support their claim.[12] In 1987, Cann, Stoneking and Wilson suggest, by RFLP analysis of human mitochondrial DNA, that humans evolved from a constrict in Africa of a single female in a small populations, ~10,00 individuals, 200,000 years ago.[13]
The era of PCR
PCR could rapidly amplify DNA from 1 molecule to billions allowing sequencing from human hairs or ancient DNA
In 1987, PCR-amplification of mtDNA was first used to determine sequences.[14] In 1991 Vigilante et al. published the seminal work on mtDNA phylogeny implicating sub-saharan Africa as the place of humans most recent common ancestors for all mtDNAs.[15] The war between out-of-Africa and multiregionalism, already simmering with the critiques of Allan Templeton, soon escalated with the paleoanthropologist, like Milford Wolpoff, getting involved.[16][17][18] In 1995, F. Ayala published his critical Science article 'The Myth about Eve', which relied on HLA-DR sequence.[19] At the time, however Ayala was not aware of rapid evolution of HLA loci via recombinatory process. In 1996, Parham and Ohta published their finds on the rapid evolution of HLA by short-distance recombination ('gene conversion' or 'abortive recombination'), weakening Ayala's claim (Parham had actually written a review a year earlier, but this had gone unnoticed).[20][21] A stream of papers would follow from both sides, many with highly flawed methods and sampling. One of the more interesting was Harris and Hey, 1998 which showed that the TMCRA (time to most recent common ancestor) for the PDHA1 gene was well in excess of 1 million years. Given a ploidy at this locus of 1.5 (3 fold higher then mtDNA) the TMRCA was more than double the expectation. While this falls into the 'fixation curve' of 1.5 ploidy (Averaging 2 female and 1 male) the suggested age of 1.8 my is close a significantly deviant p-value for the population size, possibly indicating that the human population shrank or split off of another population.[22] Oddly, the next X-linked loci they examined, Factor IX, showed a TMRCA of less than 300,000 years.[23]
Cross-linked DNA extracted from the 4,000 year-old liver of an Ancient Egyptian priest Called Nekht-Ankh.
Ancient DNA
Ancient DNA sequencing had been conducted on a limited scale up to the late 1990s when the folks at the Max Plank Institute would shock the anthropology world by sequencing DNA from an estimated 40,000 year old Neanderthal.[24][25][26] The results of that experiment is that the differences between humans living in Europe, many of which were derived from haplogroup H (CRS), Neandertals branched from humans more than 300,000 years before haplogroup H reached Europe. While the mtDNA and other studies continued to support a unique recent African origin, this new study basically answered critiques from the Neandertal side.
Genomic Sequencing
Significant progress has been made in genomic sequencing since Ingman and colleague published their finding on mitochondrial genome.[27] Several papers on genomic mtDNA have been published, there is considerable variability in the rate of evolution, and rate variation and selection are evident at many sites. In 2007 Gonder et al., proposed that a core population of humans, with greatest level of diversity and lowest selection once lived in the region of Tanzania and proximal parts of southern Africa, since humans left this part of Africa, mitochondria have been selectively evolving to new regions.[28]
Critical Progress
Critical in the history of molecular anthropology.
That molecular phylogenetics could compete with comparative anthropology for determining the proximity of species to humans.
Wilson and King realized in 1975, that while there was equity between the level of molecular evolution branching from chimp to human to putative LCA, that there was an inequity in morphological evolution. Comparative morphology based on fossils could be biased by different rates of change.[5]
Realization that in DNA there are multiple independent comparisons. Two techniques, mtDNA and hybridization converge on a single answer, chimps as a species are most closely related to humans.
The ability to resolve population sizes based on the 2N rule, proposed by Kimura in the 1950s.[29] To use that information to compare relative sizes of population and come to a conclusion about abundance that contrasted observations based on the paleontological record. While human fossils in the early and middle stone age are far more abundant than Chimpazee or Gorilla, there are few unambiguous chimpanzee or gorilla fossils from the same period
Loci that have been used in molecular phylogenetics.
^ Kottak, Conrad Phillip. Windows on Humanity. New York: McGraw-Hill, 2005.
^ A.C.Wilson and N.O.Kaplan (1963) Enzymes and nucleic acids in systematics. Proceedings of the XVI International Congress of Zoology Vol.4, pp.125-127.
^Higuchi R, Bowman B, Freiberger M, Ryder OA, Wilson AC (1984). "DNA sequences from the quagga, an extinct member of the horse family". Nature312 (5991): 282–4. doi:10.1038/312282a0. PMID6504142.
^Sibley CG, Ahlquist JE (1984). "The phylogeny of the hominoid primates, as indicated by DNA-DNA hybridization". J. Mol. Evol.20 (1): 2–15. doi:10.1007/BF02101980. PMID6429338.
^Sibley CG, Ahlquist JE (1987). "DNA hybridization evidence of hominoid phylogeny: results from an expanded data set". J. Mol. Evol.26 (1-2): 99–121. doi:10.1007/BF02111285. PMID3125341.
^Cann RL, Stoneking M, Wilson AC (1987). "Mitochondrial DNA and human evolution". Nature325 (6099): 31–6. doi:10.1038/325031a0. PMID3025745.
^Handt O, Höss M, Krings M, Pääbo S (June 1994). "Ancient DNA: methodological challenges". Experientia50 (6): 524–9. doi:10.1007/BF01921720. PMID8020612.
^Ingman M, Kaessmann H, Pääbo S, Gyllensten U (December 2000). "Mitochondrial genome variation and the origin of modern humans". Nature408 (6813): 708–13. doi:10.1038/35047064. PMID11130070.
^Gonder MK, Mortensen HM, Reed FA, de Sousa A, Tishkoff SA (March 2007). "Whole-mtDNA genome sequence analysis of ancient African lineages". Mol. Biol. Evol.24 (3): 757–68. doi:10.1093/molbev/msl209. PMID17194802.
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