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Proc Natl Acad Sci U S A. Jul 19, 1994; 91(15): 6787–6794.
PMCID: PMC44284

Molecular genetics of speciation and human origins.

Abstract

The major histocompatibility complex (MHC) plays a cardinal role in the defense of vertebrates against parasites and other pathogens. In some genes there are extensive and ancient polymorphisms that have passed from ancestral to descendant species and are shared among contemporary species. The polymorphism at the DRB1 locus, represented by 58 known alleles in humans, has existed for at least 30 million years and is shared by humans, apes, and other primates. The coalescence theory of populations genetics leads to the conclusion that the DRB1 polymorphism requires that the population ancestral to modern humans has maintained a mean effective size of 100,000 individuals over the 30-million-year persistence of this polymorphism. We explore the possibility of occasional population bottlenecks and conclude that the ancestral population could not have at any time consisted of fewer than several thousand individuals. The MHC polymorphisms exclude the theory claiming, on the basis of mitochondrial DNA polymorphisms, that a constriction down to one or few women occurred in Africa, at the transition from archaic to anatomically modern humans, some 200,000 years ago. The data are consistent with, but do not provide specific support for, the claim that human populations throughout the World were at that time replaced by populations migrating from Africa. The MHC and other molecular polymorphisms are consistent with a "multiregional" theory of Pleistocene human evolution that proposes regional continuity of human populations since the time of migrations of Homo erectus to the present, with distinctive regional selective pressures and occasional migrations between populations.

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  • Bullini L. Genetic, ecological, and ethological aspects of the speciation process. Prog Clin Biol Res. 1982;96:241–264. [PubMed]
  • Mayr E. Processes of speciation in animals. Prog Clin Biol Res. 1982;96:1–19. [PubMed]
  • Templeton AR. The theory of speciation via the founder principle. Genetics. 1980 Apr;94(4):1011–1038. [PMC free article] [PubMed]
  • Cann RL, Stoneking M, Wilson AC. Mitochondrial DNA and human evolution. Nature. 1987 Jan 1;325(6099):31–36. [PubMed]
  • Stoneking M, Jorde LB, Bhatia K, Wilson AC. Geographic variation in human mitochondrial DNA from Papua New Guinea. Genetics. 1990 Mar;124(3):717–733. [PMC free article] [PubMed]
  • Vigilant L, Stoneking M, Harpending H, Hawkes K, Wilson AC. African populations and the evolution of human mitochondrial DNA. Science. 1991 Sep 27;253(5027):1503–1507. [PubMed]
  • Bjorkman PJ, Parham P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem. 1990;59:253–288. [PubMed]
  • Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. [PubMed]
  • Brown JH, Jardetzky TS, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature. 1993 Jul 1;364(6432):33–39. [PubMed]
  • Klein J, Figueroa F. Evolution of the major histocompatibility complex. Crit Rev Immunol. 1986;6(4):295–386. [PubMed]
  • Marsh SG, Bodmer JG. HLA class II nucleotide sequences, 1991. Immunogenetics. 1991;33(5-6):321–334. [PubMed]
  • Marsh SG, Bodmer JG. HLA class II nucleotide sequences, 1992. Immunogenetics. 1993;37(2):79–94. [PubMed]
  • Bontrop RE. Nonhuman primate Mhc-DQA and -DQB second exon nucleotide sequences: a compilation. Immunogenetics. 1994;39(2):81–92. [PubMed]
  • Arden B, Klein J. Biochemical comparison of major histocompatibility complex molecules from different subspecies of Mus musculus: evidence for trans-specific evolution of alleles. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2342–2346. [PMC free article] [PubMed]
  • Figueroa F, Günther E, Klein J. MHC polymorphism pre-dating speciation. Nature. 1988 Sep 15;335(6187):265–267. [PubMed]
  • McConnell TJ, Talbot WS, McIndoe RA, Wakeland EK. The origin of MHC class II gene polymorphism within the genus Mus. Nature. 1988 Apr 14;332(6165):651–654. [PubMed]
  • Mayer WE, Jonker M, Klein D, Ivanyi P, van Seventer G, Klein J. Nucleotide sequences of chimpanzee MHC class I alleles: evidence for trans-species mode of evolution. EMBO J. 1988 Sep;7(9):2765–2774. [PMC free article] [PubMed]
  • Lawlor DA, Ward FE, Ennis PD, Jackson AP, Parham P. HLA-A and B polymorphisms predate the divergence of humans and chimpanzees. Nature. 1988 Sep 15;335(6187):268–271. [PubMed]
  • Fan WM, Kasahara M, Gutknecht J, Klein D, Mayer WE, Jonker M, Klein J. Shared class II MHC polymorphisms between humans and chimpanzees. Hum Immunol. 1989 Oct;26(2):107–121. [PubMed]
  • Gyllensten UB, Erlich HA. Ancient roots for polymorphism at the HLA-DQ alpha locus in primates. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9986–9990. [PMC free article] [PubMed]
  • Gyllensten UB, Lashkari D, Erlich HA. Allelic diversification at the class II DQB locus of the mammalian major histocompatibility complex. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1835–1839. [PMC free article] [PubMed]
  • Satta Y, O'hUigin C, Takahata N, Klein J. The synonymous substitution rate of the major histocompatibility complex loci in primates. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7480–7484. [PMC free article] [PubMed]
  • Takahata N. A simple genealogical structure of strongly balanced allelic lines and trans-species evolution of polymorphism. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2419–2423. [PMC free article] [PubMed]
  • Klein J, Takahata N. The major histocompatibility complex and the quest for origins. Immunol Rev. 1990 Feb;113:5–25. [PubMed]
  • Raup DM. The role of extinction in evolution. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6758–6763. [PMC free article] [PubMed]
  • Griffiths RC. Lines of descent in the diffusion approximation of neutral Wright-Fisher models. Theor Popul Biol. 1980 Feb;17(1):37–50. [PubMed]
  • Tajima F. Evolutionary relationship of DNA sequences in finite populations. Genetics. 1983 Oct;105(2):437–460. [PMC free article] [PubMed]
  • Takahata N, Nei M. Gene genealogy and variance of interpopulational nucleotide differences. Genetics. 1985 Jun;110(2):325–344. [PMC free article] [PubMed]
  • Takahata N. Allelic genealogy and human evolution. Mol Biol Evol. 1993 Jan;10(1):2–22. [PubMed]
  • Takahata N, Nei M. Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics. 1990 Apr;124(4):967–978. [PMC free article] [PubMed]
  • Takahata N, Satta Y, Klein J. Polymorphism and balancing selection at major histocompatibility complex loci. Genetics. 1992 Apr;130(4):925–938. [PMC free article] [PubMed]
  • Klein J, Gutknecht J, Fischer N. The major histocompatibility complex and human evolution. Trends Genet. 1990 Jan;6(1):7–11. [PubMed]
  • Hughes AL, Nei M. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature. 1988 Sep 8;335(6186):167–170. [PubMed]
  • Hughes AL, Nei M. Maintenance of MHC polymorphism. Nature. 1992 Jan 30;355(6359):402–403. [PubMed]
  • Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM. Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991 Aug 15;352(6336):595–600. [PubMed]
  • Hill AV, Elvin J, Willis AC, Aidoo M, Allsopp CE, Gotch FM, Gao XM, Takiguchi M, Greenwood BM, Townsend AR, et al. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature. 1992 Dec 3;360(6403):434–439. [PubMed]
  • Hughes AL, Nei M. Maintenance of MHC polymorphism. Nature. 1992 Jan 30;355(6359):402–403. [PubMed]
  • Miller LH. Impact of malaria on genetic polymorphism and genetic diseases in Africans and African Americans. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2415–2419. [PMC free article] [PubMed]
  • Satta Y, O'hUigin C, Takahata N, Klein J. Intensity of natural selection at the major histocompatibility complex loci. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7184–7188. [PMC free article] [PubMed]
  • Fullerton SM, Harding RM, Boyce AJ, Clegg JB. Molecular and population genetic analysis of allelic sequence diversity at the human beta-globin locus. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1805–1809. [PMC free article] [PubMed]
  • Swisher CC, 3rd, Curtis GH, Jacob T, Getty AG, Suprijo A, Widiasmoro Age of the earliest known hominids in Java, Indonesia. Science. 1994 Feb 25;263(5150):1118–1121. [PubMed]
  • Gibbons A. Rewriting--and redating--prehistory. Science. 1994 Feb 25;263(5150):1087–1088. [PubMed]
  • Stringer CB. The emergence of modern humans. Sci Am. 1990 Dec;263(6):98–104. [PubMed]
  • Stringer CB. Reconstructing recent human evolution. Philos Trans R Soc Lond B Biol Sci. 1992 Aug 29;337(1280):217–224. [PubMed]
  • Stringer CB, Andrews P. Genetic and fossil evidence for the origin of modern humans. Science. 1988 Mar 11;239(4845):1263–1268. [PubMed]
  • Templeton AR. Human origins and analysis of mitochondrial DNA sequences. Science. 1992 Feb 7;255(5045):737–737. [PubMed]
  • Ruvolo M, Zehr S, von Dornum M, Pan D, Chang B, Lin J. Mitochondrial COII sequences and modern human origins. Mol Biol Evol. 1993 Nov;10(6):1115–1135. [PubMed]
  • Waddle DM. Matrix correlation tests support a single origin for modern humans. Nature. 1994 Mar 31;368(6470):452–454. [PubMed]
  • Wolpoff MH, Spuhler JN, Smith FH, Radovcić J, Pope G, Frayer DW, Eckhardt R, Clark G. Modern human origins. Science. 1988 Aug 12;241(4867):772–774. [PubMed]
  • Deeb SS, Jorgensen AL, Battisti L, Iwasaki L, Motulsky AG. Sequence divergence of the red and green visual pigments in great apes and humans. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7262–7266. [PMC free article] [PubMed]

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