Evolutionary Anthropology 81

Issues

Human Demography in the Pleistocene: Do Mitochondrial and Nuclear Tell the Same Story?

raditionally, research on mod- genomic region of interest is selec- stable. The expected pattern under ern origins has centered tively neutral, the amount and pattern selective neutrality and constant popu- Ton questions of the time and of nucleotide variation is expected to lation size10,17 is represented by the geographical place of origin, with less be proportional to the population size,9 hatched bars in Figure 2. The left- attention given to the complex popula- and to track changes in the population shifted distribution of mtDNA poly- tion dynamics of our evolutionary his- over time.10-12 Another simplifying as- morphism is consistent with an ini- tory. Recently, however, a focus has sumption that is often valid for the tially small population that recently emerged within molecular anthropol- nuclear (and less so for the has undergone a dramatic increase in ogy that concentrates on the demo- mitochondrial genome) is that muta- size. But, on the other hand, the pat- graphic aspects of the origin of mod- tions are rare at any one base position. tern could have been the result of a 1-3 ern . A popular hypothesis For example, a common assumption history dominated by natural selec- proposes that modern human popula- that greatly facilitates the develop- tion on the mitochondria. tions passed through a bottleneck (or ment of mathematical theory is the If the demographic story told on the episodic reduction in size) in the late infinite-sites model whereby muta- basis of the mtDNA variation is accu- Middle or early Late Pleistocene, at tions are assumed to have occurred rate and represents the actual history which time there existed perhaps only only once per polymorphic site.13 of modern humans, then we expect a several thousand breeding individu- One way in which nucleotide varia- similar pattern of variation across most als, and that this was followed by a tion can be described is by the fre- other loci. Because the mitochondrial rapid, large expansion.1,2,4 Supporting quency distribution of polymorphic genome lacks recombination, its con- evidence comes largely from the pat- sites within a genomic region. For stituent genes are all linked in their tern of DNA sequence variation ob- example, when a nucleotide site is inheritance. Evidence from this ge- served in mitochondrial genes. How- polymorphic, usually just two differ- nome’s 37 constituent genes and two ever, because the mitochondrial ent bases are found at that site. If we short noncoding regions cannot be genome is only a very small fraction of count the occurrences of the least fre- taken as independent evidence. There- the entire genome, its evolutionary quent base, this will give us the fre- fore, patterns of genetic variation must history is not necessarily concordant quency class for this particular site. be compared across multiple unlinked with the history of the bulk of the present in a single se- genes from the nuclear genome. In genome, the nuclear genome. quence (for example, at positions 2, 3, units of base pairs, the nuclear ge- An important distinction can be made between evolutionary forces that and 13 in Fig. 1) represent low-fre- nome is about two hundred-thousand affect just one and those forces quency mutations and all appear in times the size of the mitochondrial that act on all the genes of a popula- frequency class one. Likewise, muta- genome and harbors 50,000 to 100,000 tion. Population-level phenomena such tions appearing in half the sequences genes. As such, it is a largely untapped as bottlenecks, expansions, popula- (positions 5, 10, 12, and 15 in Fig. 1) resource of information about our ge- tion subdivisions, and represent intermediate frequency mu- netic and populational history. events are expected to produce similar tations and appear in the highest fre- In comparing the variation at differ- patterns of genetic variation across quency class, or half the number of ent genes, the fundamental differ- many loci. In contrast, natural selec- sequences. ences among mitochondrial genes, au- tion usually affects a small region of The frequency distribution of poly- tosomal genes, and genes on other tight linkage, such as a single genetic morphic sites in the mtDNA control should be kept in mind. locus. Therefore, hypotheses about regions I and II14 is shown in Figure 2. First, unlike diploid genes, mitochon- population histories should be tested It indicates an abundance of low fre- drial genes are not maintained on two across many loci.5-8 quency polymorphisms and only a distinct chromosomes, and though small fraction of polymorphisms at they are numerous in any one , the HOW CAN DNA SEQUENCE intermediate frequency. This left- processes of replication and turnover lead to their being passed on in an VARIATION REVEAL shifted distribution is typical of hu- man mitochondrial genes.15,16 This pat- effectively haploid fashion. Second, DEMOGRAPHIC HISTORY? tern, however, is not expected when whereas autosomal genes are transmit- Under the simplifying assumption sequences have evolved neutrally and ted by both parents, mitochondrial that DNA sequence variation in the when population sizes have remained genes are solely transmitted by the 82 Evolutionary Anthropology ISSUES

discussing changes in the effective ( 11)19; 20,21 population size (Ne) of humans over () ; several X-linked time. genes, including pyruvate dehydroge- The frequency distributions of poly- nase E1␣ subunit (PDHA1)15,18; dystro- morphic sites for each nuclear phin (Dmd)22; myelin proteolipid pro- can be compared with each other and tein (Plp); and glycerol kinase (Gk).23 with mitochondrial genes to test When compared with the frequency whether they are consistent with a distribution under a neutral model single population history. Hey15 ob- (the hatched bars in Fig. 2), these served that nuclear genes show an nuclear genes show even more muta- abundance of intermediate-frequency tions than expected at intermediate polymorphisms, in contrast to the over- frequencies. abundance of low-frequency polymor- HOW DO MITOCHONDRIAL AND Figure 1. Sample of sequences from a simu- lated population showing mutated bases that NUCLEAR GENE TREES DIFFER? differ in their frequency class. In units of base pairs, the The frequency distribution of poly- nuclear genome is about morphic sites bears a fairly simple mother. In contrast, X-linked genes relationship to the overall shape of the and Y-linked genes show different two hundred-thousand gene tree. For example, a -shaped patterns. genes are times the size of the gene tree (Fig. 4) in which the vast majority of coalescent events occur found as two copies in females but mitochondrial genome only one copy in males, but can be near or at the root is typical of a transmitted by either sex; Y chromo- and harbors 50,000 to population that has undergone rapid some genes are found as single copies population growth from an initially 100,000 genes. As such, 12 in males and are transmitted solely small population. The mutations that by them. The differences in number it is a largely untapped appear on this tree are not likely to and inheritance of these different resource of information have been inherited by more than a genes have significant effects on the single DNA copy in the sample and amount of variation they harbor. This about our genetic and will tend to be at low frequency. Such is solely because of the different populational history. a star-like tree is indicated by the number of gene copies existing in the pattern of mutations observed in population at any given moment. This mtDNA sequences, which show an point will be returned to later when abundance of low-frequency muta- tions. phisms found in the mtDNA, and com- In contrast, a tree with a more bal- pared several small nuclear gene data anced branching pattern and in which sets with the patterns found in the population size has been constant (Fig. mtDNA. The statistical tests were per- formed under a model of constant population size as well as a model of rapid population growth, as hypoth- esized by Rogers and Harpending.1 In all of the contrasts, the mitochondrial and nuclear genes were inconsistent with the same demographic histories. The frequency distribution for the X-linked PDHA1 region is shown in Figure 3.18 It shows an abundance of intermediate-frequency mutations and a paucity of low-frequency mutations. This pattern produces a distribution that is right-shifted, which is exactly the opposite of the distribution for Figure 2. The frequency distribution of polymor- mitochondrial genes. Interestingly, as Figure 3. The frequency distribution of polymor- phic sites for mtDNA control regions I and II. Hey15 noted, and as data that have phic sites for the PDHA X-linked gene. Black Black bars are the observed frequencies. emerged since then indicate, the major- bars are observed frequencies. Hatched bars Hatched bars are the expected frequencies ity of nuclear regions sequenced for are the expected frequencies under con- under constant population size and assuming human populations show a similar stant population size and assuming a neutral a neutral evolutionary model.10,17 The left- evolutionary model. The right-shifted distribu- shifted distribution of the mtDNA control re- right-shifted distribution, indicating an tion of the observed frequencies is typical of gion sequences is typical of mitochondrial abundance of intermediate-frequency all known large DNA sequence data sets for genes. mutations. These include ␤-globin nuclear loci. ISSUES Evolutionary Anthropology 83

could have operated on either the mi- of mtDNA showing that human tochondrial or nuclear genome, or mtDNA samples segregate high levels both. Parsimoniously, however, the of so-called nonsynonymous polymor- mtDNA genome is the most likely can- phisms.16,24 (Nonsynonymous poly- didate, as it effectively represents one morphisms change the amino-acid gene (or tight linkage group) in con- code, whereas synonymous ones do trast to the multiple unlinked nuclear not). In this model, it is selection genes that differ from it. Also, the fact against mildly deleterious mutations that the mitochondrial genes do form that results in a reduction of variation a single linkage group suggests that at linked sites and in a shifted polymor- this genome may be especially suscep- phism distribution. Figure 4. A star-shaped genealogy from a tible to natural selection, the reason There is evidence suggesting that recently growing population with mutations being that natural selection cannot act many mutations segregating in the placed along branch lengths. The figure rep- effectively on multiple polymorphic mtDNA genome today are mildly del- resents a gene tree with DNA sequence cop- sites.15,16,24 eterious.16,26 For instance, diseases ies drawn from five different ‘‘living individu- such as Leber’s hereditary optic neu- als’’ constituting the tips of the branches at the right. ropathy (LHON) myoclonic epilepsy (MERRE) an encephalomyopathy ...afocus on (MELAS), and even Alzheimer’s dis- polymorphism ease are associated with mtDNA muta- 5) has many more mutations occur- tions.27 The fact that these mutations ring on deep (or old) branches. These frequencies permits are mildly deleterious, leading to dis- polymorphisms will tend to be at inter- direct and fairly simple eases with onset during postreproduc- mediate frequencies because all of the tive years, may help to explain why descendant DNA lineages from an old comparisons among they are found at low frequencies in branch have inherited the mutations genes that have humans.16,28 Evidence of natural selec- that arose on that branch. The poly- tion’s influence on the shape and pat- morphism at nuclear genes, such as experienced different tern of human mtDNA variation may PDHA1,18 ␤-globin,19 lipoprotein li- amounts of limit the usefulness of the mtDNA pase,20,21 dystrophin,22 and other genes genetic system for understanding hu- shows this type of pattern. Such poly- recombination. man histories. morphisms preserve an abundance of So is it resolved that the mtDNA mutations that arose early on the tree, data are a poor reflection of human a finding that is not expected if the history? No. Although there are strong ancestral human population was very In recent years, two forms of selec- differences between the mtDNA and small. tion have been emphasized for cases nuclear genes, it remains possible that But if frequency distributions go of tight linkage. First, selection for a more complicated demographic mod- hand in hand with gene tree shape, favorable mtDNA copy that spreads els could be found to fit all of the why bother with the frequency distri- rapidly through the population, known genetic data. So far, the statistical tests butions? The answer is that the ex- as a selective sweep, could have pro- have examined both sets of genes un- pected frequency distribution does not duced the pattern of human mtDNA der models of constant population size depend on recombination, whereas the variation.11,24 A sweep causes a reduc- and recent expansion.15 Recently, Fay estimation of gene trees becomes quite tion of neutral variation at linked sites. and Wu29 have shown that a model of problematic for data sets from genes The variation we see today among population reduction, followed quickly that have a history of recombination. human mtDNA copies has accumu- Thus, a focus on polymorphism fre- lated recently, explaining why it is at quencies permits direct and fairly low frequency. The result, in effect, is a simple comparisons among genes that bottleneck and expansion for just have experienced different amounts of mtDNA, not for the rest of the ge- recombination. nome. A second possible mode of natu- ral selection that could cause the RECONCILING MITOCHONDRIAL shifted pattern of variation in the mtDNA is the accumulation of many AND NUCLEAR GENES slightly deleterious mutations. Again, The conflicting patterns of variation under tight linkage, natural selection between mitochondrial and nuclear cannot act efficiently on all polymor- genes suggest they cannot both be phisms, making it possible for slightly reconciled with a common demo- deleterious mutations to rise in fre- graphic history. A simple alternative quency and contribute to a skew in the Figure 5. A genealogy from a population with constant size over time. The figure represents model is that one gene or class of polymorphism frequency distribu- a gene tree with DNA sequence copies drawn 25 genes has been shaped by natural selec- tion. Evidence in support of this from five different ‘‘living individuals’’ consti- tion. In principle, natural selection model comes from recent studies tuting the tips of the branches at the right. 84 Evolutionary Anthropology ISSUES

by expansion, could explain some of in the pattern of variation at nuclear been made that an Ne of this size the difference between the mtDNA genes. However, the nucleotide varia- contradicts an extreme multiregional and the nuclear genes. If the bottle- tion at the few nuclear loci studied to model because such a population could neck was not long, or if it was very date shows a different pattern than not have occupied the entire Old World small, then it would be possible for that at mitochondrial genes. The ex- and remained a cohesive population.2 nuclear genes to preserve some old cess of old variation on deep branches However, the relationship between Ne variation, leaving mtDNA to have lost of nuclear gene trees is strong evi- and the census of individuals in a old variation. The difference arises dence that human populations never population is a complicated one, and from the different effective sizes, as experienced a very small population is affected by a variety of factors. The described earlier, for these two classes size, at least in the time span of the effects of these factors could mean of genes. Simulating a bottleneck, Fay depth of those gene trees. Gene trees that the census size of the ancestral and Wu29 found that the frequency derived for a global sample of humans population was considerably larger distribution of polymorphisms can dif- based on nuclear DNA sequences all than is indicated by low estimates of 40 fer considerably between the two ge- Ne. Nevertheless, between an ex- nomes. Thus, it is possible that the treme multiregional model42 and Afri- different patterns of variation seen at The excess of old can-origin models there are many sce- nuclear and mitochondrial sites were, narios that include a broad geography in fact, shaped by the same history but variation on deep and gene flow. A number of plausible are out of phase with each other due to branches of nuclear intermediate multiregional models their fundamental differences in effec- have been elaborated.43,44 The critical tive population size. It remains to be gene trees is strong questions are: Exactly how geographi- seen whether this type of model can be evidence that human cally spread were the ancestors of fit to the data. modern humans? Was this population populations never subdivided? And if so, how much gene experienced a very flow occurred between subpopula- HUMAN ORIGINS small population size, at tions? The size and geographic range of Relatively ancient population subdi- the population ancestral to modern least in the time span of vision is indicated by several unlinked humans are central questions in re- the depth of those gene genetic systems. Patterns of polymor- search on human origins. Implicit in phism at the X-linked PDHA1 locus some recent African origin models is trees. indicate the presence of multiple popu- the hypothesis that the population that lations 200,000 years ago. A global evolved into modern humans was population study of ␤-globin haplo- small and localized. This hypothesis is types indicates a similar time for the appealing because it conforms to a show an excess of variation that arose onset of subdivision.19 Early popula- model in which genetic drift and local before 100,000 years ago. ␤-globin hap- tion splitting between Africans and adaptation in small populations play lotype variation extends back to nonAfricans is also indicated in re- significant roles in speciation.30,31 800,000 years,19 lipoprotein lipase ports on other genes, including segre- These explanations associate a small variation to over one million years,20,21 gating Alu insertions (137 Kyr BP),45 population size with the transforma- ZFX variation to 700,000–1.1 million mtDNA mismatch distributions (100 tion from archaic Homo sapiens to years,38 intergenic variation Xq 13.3 to Kyr BP),4 polymorphism (115 modern H. sapiens.32,33 Small popula- about 535,000 years,38 and PDHA1 Kyr BP),46 and microsatellite loci (156 tion size has also been suggested for variation to as far back as 1.86 million Kyr BP).47 Recent cladistic analyses of the emigrant population of modern H. years.18 mtDNA, Y-chromosome, and ␤-globin sapiens that left Africa.34,35 More re- Given the pattern emerging from gene regions also point to ancestral cently, others have suggested that nuclear genes, we are inspired to con- population subdivision, and seem to population contraction occurred in re- sider a broad scenario for modern indicate widespread or restricted gene sponse to the effects of a late Pleis- human origins. Patterns of nuclear flow among populations.19,46,47 tocene volcanic eruption of Mt. Toba DNA variation seem to indicate that The fossil evidence may also point in Sumatra.36 It is the pattern of varia- the ancestral modern human popula- to a relatively large and subdivided tion in the mtDNA that has been the tion was not a very small one. Instead, ancestral human population within Af- major genetic support for these histori- this population may have been rela- rica. Transitional fossils with features cal models, as the abundance of low- tively large and may have covered a intermediate between late-archaic and frequency variation is consistent with broad geographic range. If so, such a fully modern H. sapiens and sharing a a population that expanded greatly population may well have been subdi- roughly similar geologic age (between from a small size within the past vided. 200,000 and 100,000 years) come from 100,000 years.14,37 Most estimates of effective human geographically diverse regions within If the evolutionary history of mod- population size (Ne) based on a variety Africa, including Florisbad (South Af- ern humans is one of rapid expansion of loci are around 10,000.2 Some esti- rica), Omo Kibish (Ethiopia), Ngaloba from a small ancestral population, we mates are slightly higher, but not con- (Tanzania), and Djebel Irhoud (Mo- should expect to find evidence of that siderably so.18,40 The argument has rocco).50 The modern human fossils in ISSUES Evolutionary Anthropology 85 the Levant at the sites of Skhul and tion that well predates the origin of was supported by a National Insti- Qafzeh in Israel could represent a modern humans raises hope for fur- tutes of Health grant (#R55GM54684) roughly contemporaneous subpopula- ther research on the genetic basis of to JH. tion that was connected by restricted the transformation to modern hu- gene flow with African subpopula- mans. As human genes are discovered tions. through the efforts of the Human Ge- REFERENCES The presence of near-modern hu- nome Project, it might well become man features in fossils that are geo- 1 Rogers A, Harpending H. 1992. Population possible to identify the genes that make growth makes waves in the distribution of pair- graphically dispersed in Africa and us modern. How will we know these wise genetic differences. Mol Biol Evol 9:552– roughly of a similar geologic age could ‘‘modern’’ genes when we find them? If 569. easily be explained by limited gene these genes carried mutations that 2 Harpending H, Batzer MA, Gurven M, Jorde LB, Rogers A, Sherry ST. 1998. Genetic traces of flow aided by natural selection. Natu- were beneficial and that arose in our ancient demography. Proc Natl Acad Sci USA ral selection in the context of a subdi- archaic ancestors, then necessarily 95:1961–1967. vided human ancestral population they must have experienced a selective 3 Lahr M, Foley R. 1998. Towards a theory of modern human origins: geography, demography, would have increased gene flow for sweep within the past 200,000 years. and diversity in recent human evolution. Yrbk the genes that were favored. For gene These ‘‘modern’’ genes should show a Phys Anthropol 41:137–176. flow to be effective, the genes making 4 Harpending H, Sherry S, Rogers A, Stoneking us modern would, of course, have to M. 1993. The genetic structure of ancient popula- tions. Curr Anthropol 34:483–496. be favored over the entire geographic Genetic continuity at 5 Hudson RR, Kreitman M, Aguade M. 1987. A range of our ancestors. test of neutral molecular evolution based on It may be useful to note that the meeting zones creates nucleotide data. Genetics 116:153–159. subpopulations of the living baboon 6 Pamilo P, Nei M. 1988. Relationships between the potential for the gene trees and species trees. Mol Biol Evol 5:568– (Papio) could provide a model for the subpopulations of Papio 583. geographical subdivision and contact 7 Hey J. 1994. Bridging phylogenetics and popu- among ancestral human populations, to evolve as a coherent lation genetics with gene tree models. In: Schier- particularly if ancestral human sub- water B, Streit B, Wagner G, DeSalle R, editors. unit through time, Molecular ecology and evolution: approaches and populations occupied Africa and, as application. Basel: Birkhauser Verlag. p 435–449. early modern human fossils in the especially if some 8 Avise J, Wollenberg K. 1997. Phylogenetics and Levant51,52 seem to suggest, also ex- the origin of species. Proc Natl Acad Sci USA 94:7748–7755. tended into Southwest Asia. Papio is a favorable genetic alleles 9 Kimura M. 1968. Evolutionary rate at the mo- broadly distributed African species have the potential to lecular level. Nature 217:624–626. marked by phenotypic subdivision but flow preferentially from 10 Tajima F. 1989. Statistical method for testing united by gene flow at zones of over- the neutral hypothesis by DNA polymor- phism. Genetics 123:585–595. lap.51 Together, the major subpopula- subpopulation to 11 Tajima F. 1989. The effect of change in popula- tions of Papio form a continuous series subpopulation. A similar tion size on DNA polymorphism. Genetics 123: of step-clined phenotypic populations 597–601. having a ring-like geographical distri- situation might have 12 Slatkin M, Hudson R. 1991. Pairwise compari- sons of mitochondrial DNA sequences in stable bution in sub-Saharan Africa. Gene existed for and exponentially growing populations. Genetics flow is presumed or observed to occur 129:555–562. at the narrow zones where different subpopulations of 13 Kimura M. 1969. The rate of molecular evolu- tion considered from the standpoint of popula- forms are contiguous. Genetic continu- ancestral modern tion genetics. Proc Natl Acad Sci USA 63:1181– ity at meeting zones creates the poten- 1188. tial for the subpopulations of Papio to humans. 14 Vigilant L, Stoneking M, Harpending H, evolve as a coherent unit through time, Hawkes K, Wilson AC. 1991. African populations and the evolution of human mitochondrial DNA. especially if some favorable genetic Science 253:1503–1507. alleles have the potential to flow prefer- 15 Hey J. 1997. Mitochondrial and nuclear gene entially from subpopulation to sub- unique evolutionary history—a his- trees present conflicting portraits of human ori- gins. Mol Biol Evol 14:166–172. population. A similar situation might tory with a very recent coalescence, resembling a bottleneck, with a time 16 Nachman M, Brown W, Stoneking M, Aquadro have existed for subpopulations of an- C. 1996. Nonneutral mitochondrial DNA varia- cestral modern humans. If the ances- that coincides with the earliest mod- tion in humans and . Genetics 142: tral modern human population was ern human fossils. These genes should 953–963. also show a history of increased gene 17 Fu Y-X. 1995. Statistical properties of segregat- subdivided, it will be a challenge for ing sites. Theor Popul Biol 48:172–197. flow among human populations. molecular anthropologists to recon- 18 Harris E, Hey J. 1999. X chromosome evi- struct the pattern of spread, subdivi- dence for ancient human histories. Proc Natl sion, and possible regions of contact ACKNOWLEDGMENTS Acad Sci USA 96:3320–3324. 19 Harding R, Fullerton SM, Griffiths RC, Bond between and among these subpopula- We thank John Wakeley, Raj Ban- J, Cox MJ, Schneider JA, Moulin DS, Clegg JB. tions. 1997. Archaic African and Asian lineages in the daru, Richard Kliman, Carlos genetic ancestry of modern humans. Am J Hum Machado, John Relethford, Alan Genet 60:772–789. FUTURE PROSPECTS Templeton, and three reviewers for 20 Clark A, Weiss KM, Nickerson DA, Taylor SL, Buchanan A, Stengard J, Salomaa V, Vartiainen The finding that most nuclear genes Evolutionary Anthropology for helpful E, Perola M, Boerwinkle E, Sing CF. 1998. Haplo- harbor a wealth of old genetic varia- comments on this paper. This work type structure and population genetic inferences 86 Evolutionary Anthropology ISSUES from nucleotide-sequence variation in human evolutionists versus migrationists. J Hum Evol tomically modern humans. New York: Plenum lipoprotein lipase. Am J Hum Genet 63:595–612. 5:477–495. Press. p 227–249. 21 Nickerson D, Taylor SL, Weiss KM, Clark AG, 33 Wainscoat J. 1987. Out of the garden of Eden. 45 Stoneking M, Fontius JJ, Clifford SL, Soodyall Hutchinson RG, Stengard J, Salomaa V, Varti- Nature 325:13. H, Arcot SS, Saha N, Jenkins T, Tahir MA, Dein- ainen E, Boerwinkle E, Sing CF. 1998. DNA 34 Wainscoat JS, Hill AVS, Boyce AL, Flint J, inger PL, Batzer MA. 1997. Alu insertion polymor- sequence diversity in a 9.7-kb region of the hu- Hernandez M, Thein SL, Old JM, Lynch JR, phisms and human evolution: evidence for a man lipoprotein lipase gene. Nat Genet 19:233– Falusi AG. 1986. Evolutionary relationship of larger population size in Africa. Genome Res 240. human populations from an analysis of nuclear 7:1061–1071. 22 Zietkiewicz E, Yotova V, Jarnik M, Korab- DNA polymorphisms. Nature 319:491–493. 46 Nei M. 1995. Genetic support for the out-of- Laskowska M, Kidd KK, Modiano D, Scozzari R, 35 Jones JS, Rouhani S. 1986. How small was the Africa theory of human evolution. Proc Nat Acad Stoneking M, Tishkoff S, Batzer M, Labuda D. bottleneck? Nature 319:449–450. Sci USA 92:6720–6722. 1998. Genetic structure of the ancestral popula- 36 Ambrose SH. 1998. Late Pleistocene human 47 Goldstein DB, Ruiz Linares A, Cavalli-Sforza tion of modern humans. J Mol Evol 47:146–155. population bottlenecks, volcanic winter, and dif- LL, Feldman MW. 1995. Genetic absolute dating 23 Nachman M, Bauer V, Crowell SL, Aquadro C. ferentiation of modern humans. J Hum Evol based on microsatellites and the origin of modern 1998. DNA variability and recombination rates at 34:623–651. humans. Proc Natl Acad Sci USA 92:6723–6727. X-linked loci in humans. Genetics 150:1133– 37 Rogers A. 1995. Genetic evidence for a Pleis- 48 Templeton AR. 1997. Out of Africa? What do 1141. tocene population explosion. Evolution 49:608– genes tell us? Curr Opinions Genet Dev 7:841– 24 Wise C, Sraml M, Esteal S. 1998. Departure 615. 847. from neutrality at the mitochondrial NADH dehy- 38 Jaruzelska J, Zietkiewicz E, Batzer M, Cole drogenase subunit 2 gene in humans, but not in 49 Templeton AR. 1999. Human races: a genetic DEC, Moisan J-P, Scozzari R, Tavare´ S, Labuda chimpanzees. Genetics 148:409–421. and evolutionary perspective. Am Anthropol 100: D. 1999. Spatial and temporal distribution of the 632–650. 25 Charlesworth B, Morgan MT. 1995. The pat- neutral polymorphisms in the last ZFX intron: 50 Stringer C, Andrews P. 1988. Genetic and tern of neutral molecular variation under the Analysis of the haplotype structure and geneal- fossil evidence for the origin of modern humans. background selection model. Genetics 141:1619– ogy. Genetics 152:1091–1101. 1632. Science 239:1263–1268. 39 Kaessmann H, Heißig F, Haeseler A von, Pa¨a¨bo 51 Valladas H, Reyss JL, Joron G, Valladas J, 26 Templeton AR. 1996. Contingency tests of S. 1999. DNA sequence variation in a non-coding Bar-Yosef O, Vandermeersch B. 1988. Thermolu- neutrality using intra/interspecific gene trees: the region of low recombination on the human X minescence dating of Mousterian ‘‘Proto-Cro- rejection of neutrality for the evolution of the chromosome. Nature Genetics 22:78–81. mitochondrial cytochromeoxidase II gene in the Magnon’’ remains from Isreal and the origin of 40 Sherry S, Harpending H, Batzer M, Stoneking hominoid primates. Genetics 144:1263–1270. modern man. Nature 331:614–616. M. 1997. Alu evolution in human populations: 27 Wallace DC. 1994. Mitochondrial DNA muta- using the coalescent to estimate effective popula- 52 Klein RG. 1989. The human career: human tions in diseases of energy metabolism. J Bioen- tion size. Genetics 147:555–562. biological and cultural origins Chicago: The Uni- erg Biomembr 26:241–250. versity of Chicago Press. 41 Relethford JH. 1998. Genetics of modern hu- 28 Hasegawa M, Cao Y, Yang Z. 1998. Preponder- man origins and diversity. Ann Rev Anthropol 53 Jolly CJ. 1993. Species, subspecies, and ba- ance of slightly deleterious polymorphism in 27:1–23. boon systematics. In: Kimbel W, Martin L, edi- mitochondrial DNA nonsynonymous/synonymous tors. Species, species concepts, and primate evo- 42 Wolpoff M. 1989. Multiregional evolution: the rate ratio is much higher within species than lution. New York: Plenum Press. p 67–105. fossil alternative to Eden. In: Mellars P, Stringer between species. Mol Biol Evol 15:1499–1505. C, editors. The human revolution: behavioural 29 Fay JC, Wu C-I. 1999. A human population and biological perspectives on the origins of Eugene E. Harris bottleneck is not incompatible with the discor- modern humans. Princeton: Princeton University Jody Hey dance between patterns of mitochondrial and Press. p 62–108. nuclear DNA variation. Mol Biol Evol. 16:1003– Department of Genetics 43 Wolpoff MH. 1994. Multiregional evolution: a 1005. Rutgers University worldwide source for modern human popula- Nelson Biological Labs 30 Mayr E. 1942. Systematics and the origin of tions. In: Nitecki MH, Nitecki DV, editors. Origins species New York: Columbia University Press. of anatomically modern humans. New York: Ple- Busch Campus 31 Wright S. 1932. The roles of mutation, inbreed- num Press. p 175–199. Piscataway, NJ 08854-8082 ing, crossbreeding, and selection in evolution. 44 Smith F. 1994. Samples, species, and specula- E-mail: [email protected] Proc 6th Int Congress Genet 1:356–366. tions in the study of modern human origins. In: [email protected] 32 Howells WW. 1976. Explaining modern man: Nitecki MH, Nitecki DV, editors. Origins of ana- ௠ 1999 Wiley-Liss, Inc. Books Received

• Billman, BR and Feinman, GM Ginsberg, JR (eds.) (1999). Con- • Glover, TD and Barratt, CLR (edi- (eds.) (1999). Settlement Pattern servation in a Changing World. tors) (1999). Male Fertility and Studies in the Americas: Fifty Cambridge: Cambridge Univer- Infertility. New York: Cambridge Years Since Viru´. Washington, sity Press. xi ϩ 308 pp. ISBN University Press. xiv ϩ 271 pp. D.C.: Smithsonian Institution 0-521-63445-8. $80.00 (cloth) ISBN 0-521-62375-8. $74.95 Press. xviii ϩ 246 pp. ISBN • Sigurdsson, H (1999). Melting the (cloth) 1-56098-826-6. $65.00 (cloth) Earth: the History of Ideas on • • Klein, RG (1999). The Human Volcanic Eruptions. New York: Mitchell, RW, Thompson, NS, and Career: Human Biological and Cul- Oxford University Press, Inc. ix ϩ Miles, HL (editors) (1997). An- tural Origins, Second Edition. 260 pp. ISBN 0-19-510665-2 thropomorphism, Anecdotes, and Chicago: University of Chicago • Bock, GR and Cardew, G (1999). Animals. Albany: State Univer- Press. xxx ϩ 840 pp. ISBN 0-226- Homology. New York: John Wiley sity of New York Press. xx ϩ 518 43963-1. $45.00 (cloth) & Sons, Inc. viii ϩ 256 pp. ISBN pp. ISBN 0-7914-3126-6. $21.95 • Mace, GM, Balmford, A, and 0-471-98493-0. $180.00 (cloth) (paper)