The Implications of Mitochondrial DNA on Theories of Modern Origins

Allan Wilson, and Chris Stringer, propose that anatomically modern evolved as a The introduction of molecular biology separate species, roughly 200,000 years ago in into paleoanthropology has established a new (Stringer and Andrews 1988). Known discipline, molecular . Debates as the Recent African Origin Model [RAO]! it with regards to the origin of modern Homo also postulates that this very same species sapiens have grown increasingly heated since spread throughout the Old World, replacing its advent. Any hypothesis of human origins populations of archaic humans as a result of proposed on the basis of fossil records can their better-adapted traits. now be examined, in light of genetic data, At the opposite end of the spectrum more quantitatively than ever before. lies the Multiregional Continuity camp, Quantitative and objective information about headed by Milford Wolpoff and Alan Thorne the evolutionary history of the human species (1991). In a nutshell, Wolpoff believes that can now be gathered through molecular the fossil evidence for biology. It has provided new insights into our clearly demonstrates that the living groups of genetic divergence from apes and into the way humankind came not only from Africa, but in which humans are related to one another also from ancestors who lived in the same (Cann et al. 1987). The various theories regions as they do now, as much as a million surrounding the origin of anatomically years ago. The basis of this theory lies on modern humans have been the hottest substantial gene flow among small controversy in anthropology over the last two populations that were thinly scattered across decades. The focus of molecular biology, as three continents. For a diagrammatic it applies to paleo-anthropology, has been representation of these two leading models of centered on a single organelle within the modern human origins refer to Figure 1. human cell, the mitochondrion. It is hoped According to the Multiregional model, that with the help of mitochondria, the hottest the appearance of Homo sapiens was debate in anthropology will move one step primarily the result of gene flow, local closer to being resolved. selection, and genetic drift; thus, simply a continuation of long-term trends in human The Combatants: evolution (Wolpoff 1996). Such a trend Most anthropologists, and other would have occurred through the resorting of respected authorities on the subject are, at the same genetic material under selection, as present, divided among two leading camps with differing theories on modern human origins. One camp, highly supported by the 1 Also known by various other names, i.e. Out of likes of Rebecca Cann, Mark Stoneking, Afiica, Single Origin Model, Replacement Model opposed to evolution. The most active Neanderthals and Java Man, respectively proponents of such a scenario have even gone (Stringer 1990). Thus, intermediate forms so far as to suggest that the title of Homo between archaic and modem species should sapiens be re-allocated to include all be found everywhere, not just in Africa. specimens presently included under the title Unfortunately for Wolpoff and his followers, of Homo erectus. If this account is correct, such intermediate formshave not been found. then the large noses of Europeans and the At least not yet. robust cheekbones of Australian Aborigines, for example, would derive from the

The "Out of Africa" model states that modem differentiated features in the process. As Homo sapiens evolved in Africa recently and such, this theory would imply that archaic quickly expanded into the rest of the Old lineages, such as the European Neanderthals World, replacing existing populations of and the East Asian Solo Man, mixed little, if Homo erectus and archaic Homo sapiens. not at all, with early modem humans, but The "Multiregional Evolution" model states instead were replaced by them (Stringer that Homo erectus populations expanded out 1990). Thus, genetic and morphological of Africa close to 2 million years ago and variation should be the greatest within African became established throughout the Old World populations. Moreover, African gene by means of gene flow between local frequencies should be sharply distinguished populations. Conversely, the model of a from those found among non-African recent African origin proposes that a racially populations. Unlike the Wolpoffian view, undifferentiated stock of modem humans intermediate forms between archaic and evolved in Africa and spread throughout the modem species should not appear outside of world, developing geographically Africa, and as stated earlier, this happens to be the case. Interestingly enough, and widespread appearance of modem Homo consistent with our current fossil record, the sapiens. single origin model also predicts that the Both models predict that modem earliest record of modem Homo sapiens characteristics evolved late and that regional, should occur in Mrica (i.e. the continent of characteristics evolved locally. Where they origin) and the youngest record should occur disagree is in the timing of the regional at the peripheries of the radiation (Stringer differentiation. Multiregionalists claim that and Andrews 1988). Perhaps one of the most differences in morphological features convincing arguments for the Replacement developed prior to the appearance of modem Model is its independence from parallel ones, whereas proponents of the Recent evolution. A single origin would minimize African Origin model would invert this order. the amount of parallel evolution required to Predictions of the two models are summarized produce the characteristics seen among the below in Table 1.

Aspect Multiregional Evolution Recent African Evolution

1. Geographic patterning of Continuity of pattern from middle Continuity of pattern only from human evolution Pleistocene to present late Pleistocene appearance of H. sapiens to present Interpopulation differences are Interpopulation differences high, greatest between each relatively low, greatest peripheral area between African and non- African populations Intrapopulation variation greatest Intrapopulation variation greatest at center of human range in African populations

2. Regional continuity and Transitional fossils widespread Transitional fossils restricted to The establishment of Africa, population replace- Homo sapiens ment elsewhere Modem regional characters of Modem regional characters of high antiquity at peripheries low antiquity at peripheries (except Africa) No consistent temporal pattern Phased establishment of Homo of appearance of Homo sapiens suite of characters: sapiens characters between i) Africa, ii) S.W. Asia, areas iii) other areas

3. Selective and behavioral Factors varied and widespread, Factors special and localized in factors involved in the perhaps related to technology; Africa; behavorial origin of Homo sapiens local behavioral continuity discontinuities expected expected outside Africa

after Stringer and Andrews, 1998 Table 1. Theoretical Predictions from Models of Homo sapiens Evolution

Dial "M" For Mitochondria: who favor multiregionalism, rely on the study Paleoanthropologists like Wolpoff, of external evidence disclosed in bones and teeth of the fossil record to explain the The importance of mitochondria to the emergence of modern humans. On the other study of modern human origins is not their hand, geneticists rely on the evidence explicit value to the life of the cell itself, but rather to to the internal structures of living cells. In two key properties: i) its rate of mutation, and particular, the organelle that contributes the ii) its mode of inheritance. The rate of most to our understanding of modern human mutation in mtDNA is several times faster origins is the mitochondrion. than in the nucleus (Cann et al. 1987). Mitochondria, found in all mammalian Furthermore, unlike nuclear DNA, mtDNA is cells, are bacterium-sized organelles that inherited from the mother alone, and thus provide a location for a variety of cellular does not recombine (Wilson and Cann 1992). functions; namely, lipid metabolism, the citric Due to its rapid and steady mutations, acid cycle, cellular respiration, and oxidative mitochondrial DNA behaves like a fast- phosphorylation (Schon 1993). They have ticking clock which allows for identification sometimes been referred to as the of recent genetic changes. According to "powerhouse" of the cell. Not only is their Stringer (1990:99) these "molecular clocks function vital to the life of the cell, but their can be reliable only if two assumptions hold evolutionary history provides insight into the true: the genetic similarities of organisms more unique properties of the mitochondrion. must be a function of their relatedness and According to the Endosymbiotic Theory, directly proportional to the recency of their spearheaded by Lynn Margulis, it is believed divergence from a common ancestor". Thus, that, billions of years ago, mitochondria were the mutations used to 'set' the molecular free-living bacteria that established a clock must be inconsequential from the symbiotic relationship with their primordial standpoint of , and these host organisms (Campbell 1996). Eventually, mutations must accumulate at fairly steady these independent bacteria were integrated rates on surviving lineages. If natural into the life cycle of their hosts' cells and selection does not favor these mutations over became one with them, resulting in our typical others, then the only reason one person's eukaryotic cell. Spawning from this unique mitochondrial DNA differs from another's is evolutionary history, it is no surprise that simply the passage of time. This is the crux mitochondria contain their own DNA, called of the hypothesis. Due to mitochondrial DNA (mtDNA). In fact, the its high rate of mutation, mtDNA is suitable mitochondrion is the only cellular organelle, for the phylogenetic analyses among closely other than the nucleus, to contain its own related species and within species. Also, the DNA. Each human mitochondrion carries its maternal inheritance of mtDNA allows us to own 16,000 base-pair loop of DNA that trace the evolution of a maternal lineage by geneticists have been able to sequence in its using mtDNA sequencing (Adachi and entirety. The mtDNA contains 37 different Hasegawa 1995). Put simply, based upon the genes: 22 tRNA's2, 2 rRNA's3, and 13 above characteristics, the Mitochondrial Eve mRNA's4 (Schon 1993). hypothesis claims that all human mitochondrial DNA must have an ultimate common female ancestor. Perhaps and Rebecca Cann (1992:70) put it best: Imagine a static population that always contains 15 mothers. Every new generation must works involving mtDNA analysis. contain 15 daughters, Mitochondrial DNA work is based upon two but some mothers will ideas (Oxnard 1995). The first is a study of fail to produce a patterns of similarity and difference in daughter, whereas mtDNA sequences, which attempts to others will produce discover how living populations are related to two or more. Because each other through maternal ancestors. The maternal lineages die second idea depends upon an analysis of the out whenever there is rates at which these differences have been no daughter to carry acquired. Ifthere is a constant rate of change, on, it is only a matter then the amount of difference is directly of time before all but proportional to the amount of time. In 1981 one lineage disappears. the complete sequence and gene organization of the human mitochondrial was The lucky woman whose lineage survived identified (Anderson et ai. 1981). Knowledge might be referred to as "Eve". If of the complete mtDNA sequence made it mitochondrial DNA mutates at a constant possible to construct detailed restriction site rate, as it is thought to do, geneticists could, maps by comparing observed restriction theoretically, calculate the amount of time enzyme fragment patterns with those needed to amass the differences among living predicted from the published sequence. The human populations, and thus determine the floodgates had been opened, and an enormous date when all humans diverged from a single body of data poured in. female ancestor. As stated previously, there are three Paleoanthropology and its theories aspects to the African Eve hypothesis: i) all therein, suffer from several limitations; the mtDNA can be traced back to a single most serious of which centers around ancestor; ii) this ancestor probably lived in paradigms. In principle, fossils cannot be Africa; and iii) this ancestor probably lived objectively defined. The characteristics that about 200,000 years ago. Perhaps the most the fossils take on are a direct result of the important prediction of the African Eve model to which the paleoanthropologist is hypothesis lies in the date it provides for a testing. Fortunately for advocates of common ancestor. Narrowing a timeframe molecular biology, this is not the case. for the origin of this ancestor has drastic Because they have not been defined by any ramifications on other theories of modern particular evolutionary model, genes become human origins. objective sources of information. In 1987, in the first study of this kind, Furthermore, due to this new objective Rebecca Cann, Mark Stoneking, and the late evidence, gene sequences are empirically Allan Wilson compared the mtDNA types of verifiable and not shaped by paradigms. 147 individuals in an attempt to hone in on Thus, fossils help to fill in the knowledge of the date of the common ancestor. Assuming how biological processes worked in the past, that mtDNA sequence divergence but they should not blind us to new lines of accumulates at a constant rate of 2%-4% per evidence or interpretations. million years, Cann et al. 's study implied that the common ancestor of all surviving mtDNA types existed somewhere between 140,000 to 290,000 years ago. The time span is quite large, but was calculated deliberately in order to insure a 95% confidence interval. Without contains. By comparing the average amount knowledge of the African Eve hypothesis, two of sequence divergence between humans and earlier studies performed in 1983 also yielded , Vigilant et at. were able to interesting results. A study by Johnson et al. extrapolate a mtDNA sequence divergence for found that Africans possess the greatest humans at 2.87% per million years. From this amount of mtDNA variability. Furthermore, newly calibrated rate of evolution it was another study by Greenberg et al. concluded determined that the ancestor existed about that Black American mtDNA types showed 166,00 to 249,000 years ago (Vigilant el at. more diversity, implying that there must be a 1991). Interestingly enough, with the common African ancestor (Cann et al. 1987). weaknesses of Cann et at.'s study resolved, Cann et al.'s initial study was met with the results of Vigilant et at.'s study proved to skepticism and criticism. First, they were be consistent with Cann et al.' s. chastised for the make-up of their sample. Further studies over the past number Rather than using native African individuals, of years have also yielded supporting results Black Americans were substituted. Another [see Table 2]. Despite the variety of methods weakness of the Cann et al. study is that it and data sets used (the details of which are used an indirect method of comparing too great to include here), almost all of these mtDNAs, namely restriction analysis. confidence intervals place the age of the Moreover, the midpoint method for rooting human mtDNA ancestor within the range of the common ancestor on the mtDNA tree is 50,000 to 500,000 years. also inferior. Lastly, the assumed rate of2%- In summary, all of the available data 4% sequence divergence maybe an inadequate on mtDNA studies point to two conclusions. calibration. First, present-day mitochondrial lineages can It was not until 1991 that these be traced back to an ancestor originating weaknesses were addressed in a study by somewhere between 50,000 and 500,000 Vigilant et at. The study included 121 native years ago. Second, based upon phylogenetic Africans from various sub-Saharan trees using maximum parsimony, this ancestor populations as well as an additional 68 probably lived in Africa. Thus, the three individuals from other corners of the globe predictions made by the African Eve (Vigilant et at. 1991). Instead of the midpoint hypothesis have been buttressed by current method, Vigilant et al.'s study used the mtDNA evidence. outgroup method. This method uses a sequence from another species (the 'outgroup'), such as an African ape, to place the human mtDNA ancestor on the tree, and As stated earlier, the African Eve as such, does not rely on the assumption that hypothesis rests upon three fundamental ideas the rate of evolution is the same in all lineages (Stoneking 1997). Firstly, due to the (Vigilant et al. 1991). Vigilant et al.' s study mitochondrion's unique mode of inheritance also relied on the polymerase chain reaction and simple genome structure, it is believed [PCR] rather than restriction analysis. In that all mtDNA can be traced back to a single short, PCR allows the researcher to isolate a ancestor. Secondly, this ancestor probably fragment of DNA and from this fragment lived in Africa. Thirdly, this ancestor lived make an infinite amount of identical copies. around 200,000 years ago. Let us now In this way, one stretch of DNA is amplified consider each of these aspects in turn. to the point where the researcher can read the literal, word-for-word genetic code it Table 2. Estimates of the Age of the Human mtDNA Ancestor, and Associated 95% Confidence Intervals (C.I.)

Hasegawa and Horai, 1991 280,000 180,000-380,000 Pesole et aI., 1992 400,000 200,000-600,000 Nei, 1992 207,000 110,000-504,000 Stoneking et aI., 1992 135,000 63,000-386,000 Tamura and Nei, 1993 160,000 80,000-480,000 Hasegawa et aI., 1993" 211,000 0-433,000 Hasegawa et aI., 1993b 101,000 0-205,000 Templeton, 1993 213,000 102,000-389,000 Ruvolo et aI., 1993 298,000 129,000-536,000 Horai et aI., 1995 143,000 107,000-179,000

abased on control region sequences ~ased on coding sequences

As students of science, and more this aspect of the African Eve hypothesis is specifically, anthropology, the majority of us the idea that this common ancestor is a single have dismissed the notion of creationism and woman from whom all life sprang; hence the have adopted an evolutionist perspective. notion of "Eve". However, the mtDNA Thus, we can apply this notion of evolution to ancestor was not the only individual alive; she our current debate. Assuming that there was was a member of a particular population. But a single origin of life on this planet and the mtDNA types of her contemporaries assuming that all things are descended from ultimately became extinct because they, or this point, then logically, it must follow that their descendents, left either no offspring or all of the variation in any segment of DNA - only male offspring. "Eve" as we call her, be it nuclear or mitochondrial - must trace was not the first woman on the planet; she back to just one ancestor in a previous too, had ancestors, but she represents the generation. Therefore, by tracing the history point at which all contemporary mtDNA types of our present-day mtDNA lineages, we coalesce (Leakey 1994). should find an ancestor to whom all our lineagesbelong. A commonmisconception of

Africans and } non-Africans Figure 2. Simplified Branching of the mtDNA The maternal, haploid inheritance of divergence, NOT a population divergence. It mtDNA means that phylogenetic analysis is has also been shown that genetic divergences relatively straightforward (Campbell, 1996). tend to precede population divergences Since the only source of new variation in (Stoneking 1997). It follows then, that if the mtDNA is provided by mutation, the number human mtDNA ancestor did not live more of mutations separating two mtDNA types than 500,000 years ago, then all non-African reflect how closely those types are related. As human populations are no more than 500,000 such, the most parsimonious phylogenetic years old themselves. This is clearly trees usually contain two primary branches: incompatible with Multiregional Evolution one consisting of entirely African mtDNA, which holds that human population and the other consisting of both African and differences should be 1 to 1.5 million years all non-African mtDNA [see Fig. 2]. The old, and hence genetic divergences should be simplest explanation for this configuration is older (Wolpoff and Thome 1991). to suppose that the common ancestor is indeed African in origin. Furthermore, in all studies to date of human mtDNA variation, it has been shown that modem African So where are we? We still have our populations have the greatest mtDNA two leading contenders with different theories variability, followed by Asians and Europeans on the origin of modem Homo sapiens and respectively (Vigilant et al. 1991). The fact who are still at war with one another. On one that Africans have the largest mtDNA hand we have the Recent African Origin diversity indicates that they have accumulated model which states that modem humans the most mtDNA variations; and as such, the evolved as a separate species recently in argument for an African origin states that the Africa and then spread to replace more population with the most diversity is likely to archaic populations. On the other hand lies be the ancestral population. Moreover, the Multiregional Evolution with its hypothesis mtDNA diversity in Africa appears to that modem Homo sapiens are about 2 million encompass all of the diversity found outside years old and that modem human traits of Africa, keeping with an African origin. evolved in geographically diverse locations The age of the common ancestor is, and then spread throughout the species via perhaps, the most vital component to the gene flow and gene drift. Unfortunately for worldwide acceptance of the African Eve the proponents of each respective model, hypothesis. There are two essential aspects to fossil evidence alone is not enough, at this estimating the age of "Eve": i) determining time, to settle the dispute. the amount of sequence divergence that has It now seems as though the war has accumulated since the existence of the been transferred onto the genetic battlefield. ancestor, and ii) determining the rate of Fortunately for us, gene sequences are human mtDNA sequence divergence. virtually free of prejudices. Therefore, Calibrating the rate of sequence divergence to are objective and empirically a finer point will continue as technology verifiable sources of information. progresses. On the other hand, the amount of Mitochondrial DNA work has yielded three divergence is easily determined from significant conclusions: I) mtDNA types can phylogenetic trees (current age estimates are be traced back through time towards a outlined in Table 2). What is key is that the common ancestor; ii) this mtDNA common age of the mtDNA ancestor marks a genetic ancestor lived in Africa; and iii) this mtDNA common ancestor probably lived around California: The Benjamin/Cummings 200,000 years ago. The absence of human Publishing Company, Inc. mtDNA types that diverged from one another more than 280,000 years ago leads to the Cann, R.L., Stoneking, M., and AC Wilson implication that the migrating human 1987. Mitochondrial DNA and populations from Africa probably replaced the human evolution. Nature 325:31-36. resident European and Asian populations that descended from earlier migrations of Homo Leakey, R. 1994. 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Singapore: World Scientific. existing fossil record, new discoveries of key elements and the growing body of genetic Schon, E.A 1993. "Mitochondria." In: data, the Recent African Origin model should Mitochondrial DNA in Human one day land its one-two punch that sends the Pathology. DiMauro S, Wallace DC, Multiregional Evolution model down to the (ed.). pp.I-7. New York: Raven canvas. Press.

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