At present, the direct evidence for Neanderthal genetic variation and gene phylogeny is limited to the control region of the mitochondrial DNA (mtDNA). Neanderthal mtDNA sequences are divergent from those of recent humans. This fact, when coupled with the assumptions of selective neutrality and a recently expanding human population, argues for the complete and utter extinction of Neanderthals without living issue. But an alternative hypothesis is that human mtDNA has recently undergone an episode of positive selection, or a “selective sweep.” Five converging lines of evidence suggest that mtDNA has undergone recent positive selection: (1) mtDNA variants in living humans are associated with life history and metabolic traits that changed dramatically during recent human evolution; (2) Statistical tests show that the distribution of human mtDNA variation is clearly inconsistent with neutrality; (3) Nuclear genomic variation is not consistent with a single recent population expansion as necessary to explain human mtDNA variation; (4) A neutral mtDNA necessitates a population replacement to explain its pattern of variation, but many autosomal and X chromosomal loci show strong phylogeographic or genealogical evidence for the survival of archaic human gene lineages and therefore reject population replacement; and (5) Anatomical and archaeological evidence shows some degree of anatomical and behavioral continuity between Upper Paleolithic Neanderthals and later Europeans and likewise reject population replacement. The hypothesis of positive selection on mtDNA is in accord with recent estimates of genome-wide rates of selection and is contradicted by no known evidence. Molecular and comparative evidence further suggests that the current pattern of human mtDNA variation represents only the most recent episode of positive selection among many during human evolution. Selection on mtDNA cannot prove that other Neanderthal genomic lineages survived, although such survival may be suggested by other anatomical and genetic evidence. Nevertheless, the substantial probability of such selection renders Neanderthal mtDNA variation phylogenetically uninformative.
Keywords
- Positive selection
- adaptation
- demographic inference
- molecular evolution
- selective sweep
This is a preview of subscription content, access via your institution.
Buying options
Preview
Unable to display preview. Download preview PDF.
References
Ambrose, S.H., 1998. Late Pleistocene human population bottlenecks, volcanic winter and differentiation of modern humans. J. Hum. Evol. 34, 623–652.
Arnason, U., Gullberg, A., Janke, A., Xu, X., 1996. Pattern and timing of evolutionary divergences among hominoids based on analyses of complete mtDNAs. J. Mol. Evol. 43, 650–661.
Baird, D.M., Coleman, J., Rosser, Z.H., Royle, N.J., 2000. High levels of sequence polymorphism and linkage disequilibrium at the telomere of 12q: implications for telomere biology and human evolution. Am. J. Hum. Genet. 66, 235–250.
Bar-Yosef, O., 2002. The Upper Paleolithic revolution. Ann. Rev. Anthropol. 31, 363–393.
Biraben, J.-N., 1979. Essai sur l’evolution du nombre des hommes. Population 1, 13–25.
Biraben, J.-N., 2003. Lévolution du nombre des hommes. Population et Sociétés 394, 1–4.
Bräuer, G., 1984. A craniological appoach to the origin of anatomically modern Homo sapiens in Africa and implications for the appearance of modern Europeans. In: Smith, F.H., Spencer, F. (Eds.), The Origins of Modern Humans: A World Survey of the Fossil Evidence. Alan R. Liss, New York, pp. 327–410.
Bräuer, G., Stringer, C., 1997. Models, polarization, and perspectives on modern human origins. In: Clark, G.A., Willermet, C.M. (Eds.), Conceptual Issues in Modern Human Origins Research. Aldine de Gruyter, New York, pp. 191–201.
Bräuer, G., Collard, M., Stringer, C., 2004. On the reliability of recent tests of the Out of Africa hypothesis for modern human origins. Anat. Rec. 279A, 701–707.
Cann, R.L., Stoneking, M., Wilson, A.C., 1987. Mitochondrial DNA and human evolution. Nature 325, 31–36.
Caramelli, D., Lalueza-Fox, C., Vernesi, C., Lari, M., Casoli, A., Mallegni, F., Chiarelli, B., Dupanloup, I., Bertranpetit, J., Barbujani, G., Bertorelle, G., 2003. Evidence for a genetic discontinuity between Neandertals and 24,000-year-old anatomically modern Europeans. Proc. Natl. Acad. Sci. U.S.A. 100, 6593–6597.
Caspari, R., Lee, S.-H., 2004. Older age becomes common late in human evolution. Proc. Natl. Acad. Sci. U.S.A. 101, 10,895–10,900.
Coale, A.J., 1974. The history of the human population. Sci. Am. 231, 40–52.
Currat, M., Excoffier, L., 2004. Modern humans did not admix with Neanderthals during their range expansion into Europe. PLoS Biol. 2, e421.
Duarte, C., Maurício, J., Pettitt, P.B., Souto, P., Trinkaus, E., van der Plicht, H., Zilhão, J., 1999. The early Upper Paleolithic human skeleton from the Abrigo do Lagar Velho (Portugal) and modern human emergence in Iberia. Proc. Natl. Acad. Sci. U.S.A. 96, 7604–7609.
Enard, W., Przeworski, M., Fisher, S.E., Lai, C.S., Wiebe, V., Kitano, T., Monasco, A.P., Pääbo, S., 2002. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, 869–872.
Eswaran, V., Harpending, H., Rogers, A.R., 2005. Genomics refutes an exclusively African origin of humans. J. Hum. Evol. 49, 1–154.
Fay, J.C., Wu, C.-I., 1999. A human population bottleneck can account for the discordance between patterns of mitochondrial versus nuclear DNA variation. Mol. Biol. Evol. 16, 1003–1005.
Fay, J.C., Wyckoff, G.J., Wu, C.-I., 2001. Positive and negative selection on the human genome. Genetics 158, 1227–1254.
Foley, R.A., 1998. Genes, evolution and diversity: yet another look at the problem of modern human origins. Evol. Anthropol. 6, 191–193.
Frayer, D.W., 1993. Evolution at the European edge: Neanderthal and Upper Paleolithic relationships. Préhistoire Européenne 2, 9–69.
Frayer, D.W., Wolpoff, M.H., Smith, F.H., Thorne, A.G., Pope, G.G., 1993. The fossil evidence for modern human origins. Am. Anthropol. 95, 14–50.
Garrigan, D., Mobasher, Z., Severson, T., Wilder, J.A., Hammer, M.F., 2005. Evidence for archaic Asian ancestry on the human X chromosome. Mol. Biol. Evol. 22, 189–192.
Gutiérrez, G., Sánchez, D., Marín, A., 2002. A reanalysis of the ancient mitochondrial DNA sequences recovered from Neandertal bones. Mol. Biol. Evol. 19, 1359–1366.
Haak, W., Forster, P., Bramanti, B., Matsumura, S., Brandt, G., Tänzer, M., Villems, R., Renfrew, C., Gronenborn, D., Alt, K.W., Burger, J., 2005. Ancient DNA from the first European farmers in 7500-year-old Neolithic sites. Science 310, 1016–1018.
Hardy, J., Pittman, A., Myers, A., Gwinn-Hardy, K., Fung, H.C., de Silva, R., Hutton, M., Duckworth, J., 2005. Evidence suggesting that Homo neanderthalensis contributed the H2 MAPT haplotype to Homo sapiens. Biochem. Soc. Trans. 33, 582–585.
Harpending, H., Rogers, A., 2000. Genetic perspectives on human origins and differentiation. Ann. Rev. Genomics Hum. Genet. 1, 361–385.
Harpending, H.C., Sherry, S.T., Rogers, A.R., Stoneking, M., 1993. The genetic structure of ancient human populations. Curr. Anthropol. 34, 483–496.
Harpending, H.C., Batzer, M.A., Gurven, M., Jorde, L.B., Rogers, A.R., Sherry, S.T., 1998. Genetic traces of ancient demography. Proc. Natl. Acad. Sci. U.S.A. 95, 1961–1967.
Hawks, J., Wolpoff, M.H., 2001. Paleoanthropology and the population genetics of ancient genes. Am. J. Phys. Anthropol. 114, 269–272.
Hawks, J., Hunley, K., Lee, S.-H., Wolpoff, M.H., 2000a. Bottlenecks and Pleistocene human evolution. Mol. Biol. Evol. 17, 2–22.
Hawks, J., Oh, S., Hunley, K., Dobson, S., Cabana, G., Dayalu, P., Wolpoff, M.H., 2000b. An Australasian test of the recent African origin theory using the WLH-50 calvarium. J. Hum. Evol. 39, 1–22.
Hawks, J.D., 1999. The evolution of human population size: A synthesis of fossil, archaeological, and genetic data. Ph.D. Dissertation, University of Michigan, Ann Arbor, MI.
Howell, N., Kubacka, I., Mackey, D., 1996. How rapidly does the human mitochondrial genome evolve? Am. J. Hum. Genet. 59, 501–509.
Howells, W.W., 1942. Fossil man and the origin of races. Am. Anthropol. 44, 182–193.
Jorde, L.B., Bamshad, M., Rogers, A.R., 1998. Using mitochondrial and nuclear DNA markers to reconstruct human evolution. BioEssays 20, 126–136.
Kimmel, M., Chakraborty, R., King, J., Bamshad, M., Watkins, W., Jorde, L.B., 1997. Signatures of population expansion in microsatellite repeat data. Genetics 148, 1921–1930.
Kivisild, T., Shen, P., Wall, D.P., Do, B., Sung, R., Davis, K.K., Passarino, G., Underhill, P.A., Scharfe, C., Torroni, A., Scozzari, R., Modiano, D., Coppa, A., deKnjiff, P., Feldman, M.W., Cavalli-Sforza, L.L., Oefner, P.J., 2006. The role of selection in the evolution of human mitochondrial genomes. Genetics 172, 373–387.
Klein, R., 1999. The Human Career: Human Biological and Cultural Origins. 2nd Edition. University of Chicago Press, Chicago.
Klein, R., Edgar, B., 2002. The Dawn of Human Culture. John Wiley and Sons, New York.
Knight, A., 2003. The phylogenetic relationship of Neandertal and modern human mitochondrial DNAs based on informative nucleotide sites. J. Hum. Evol. 44, 627–632.
Kreitman, M., 2000. Methods to detect selection in populations with applications to the human. Ann. Rev. Genom. Hum. Genet. 1, 539–559.
Krings, M., Stone, A., Schmitz, R.W., Krainitzid, H., Stoneking, M., Pääbo, S., 1997. Neandertal DNA sequences and the origin of modern humans. Cell 90, 1–20.
Krings, M., Geisert, H., Schmitz, R.W., Krainitzki, S.P., 1999. DNA sequence of the mitochondrial hypervariable region ii from the Neandertal type specimen. Proc. Natl. Acad. Sci. U.S.A. 96, 5581–5585.
Krings, M., Capelli, C., Tachentacher, F., Geisert, H., Meyer, S., von Haeseler, A., Grossschmidt, K., Possnert, G., Paunovic, M., Pääbo, S., 2000. A view of neandertal genetic diversity. Nat. Genet. 26, 144–146.
Lahr, M.M., 1996. The Evolution of Modern Human Diversity: A Study of Cranial Variation.
Lowell, B.B., Shulman, G.I., 2005. Mitochondrial dysfunction and Type 2 diabetes. Science 307, 384–397.
Macaulay, V., Hill, C., Achilli, A., Rengo, C., Clarke, D., Meehan, W., Blackburn, J., Semino, O., Scozzari, R., Cruciani, F., Taha, A., Shaari, N.K., Raha, J.M., Ismail, P., Zainuddin, Z., Goodwin, W., Bulbeck, D., Bandelt, H.-J., Oppenheimer, S., Torroni, A., Richards, M., 2005. Single, rapid coastal settlement of Asia revealed by analysis of complete mitochondrial genomes. Science 308, 1034–1036.
Manderscheid, E.J., Rogers, A.R., 1996. Genetic admixture in the Late Pleistocene. Am. J. Phys. Anthropol. 100, 1–5.
Marth, G.T., Czabarka, E., Murvai, J., Sherry, S.T., 2004. The allele frequency spectrum in genomewide human variation data reveals signals of differential demographic history in three large world populations. Genetics 166, 351–372.
McDonald, J.H., Kreitman, M., 1991. Adaptive protein evolution at the Adh locus in Drosophila. Nature 351, 652–654.
Merriwether, D., Clark, A.G., Ballinger, S.W., Schurr, T.G., Soodyall, H., Jenkins, T., Sherry, S.T., Wallace, D.C., 1991. The structure of human mitochondrial DNA variation. J. Mol. Evol. 33, 543–555.
Mishmar, D., Ruiz-Pesini, E., Golik, P., Macaulay, V., Clark, A.G., Hosseini, S., Brandon, M., Easley, K., Chen, E., Brown, M.D., Sukernik, R.I., Olckers, A., Wallace, D.C., 2003. Natural selection shaped regional mtDNA variation in humans. Proc. Natl. Acad. Sci. U.S.A. 100, 171–176.
Niemi, A.-K., Majamaa, K., 2005. Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Eur. J. Hum. Genet. 13, 965–969.
Niemi, A.-K., Moilanen, J.S., Tanaka, M., Hervonen, A., Hurme, M., Lehtimäki, T., Arai, Y., Hirose, N., Majamaa, K., 2005. A combination of three common inherited itochondrialDNApolymorphisms promotes longevity in Finnish and Japanese subjects. Eur. J. Hum. Genet. 13, 166–170.
Nordborg, M., 1998. On the probability of Neanderthal ancestry. Am. J. Hum. Genet. 63, 1237–1240.
Pearson, O., 2003. Has the combination of genetic and fossil evidence solved the riddle of modern human origins? Evol. Anthropol. 13, 145–159.
Protsch, R.R., 1975. The absolute dating of Upper Pleistocene sub-Saharan fossil hominids and their place in human evolution. J. Hum. Evol. 4, 297–322.
Przeworski, M., Hudson, R.R., DiRienzo, A., 2000. Adjusting the focus on human variation. Trends Genet. 16, 296–302.
Ptak, S.E., Przeworski, M., 2002. Evidence for population growth in humans is confounded by fine-scale population structure. Trends Genet. 18, 559–563.
Richards, M., 2003. The Neolithic invasion of Europe. Ann. Rev. Anthropol. 32, 135–162.
Ruiz-Pesini, E., Mishmar, D., Brandon, M., Procaccio, V., Wallace, D.C., 2004. Effects of purifying and adaptive selection on regional variation in human mtDNA. Science 303, 223–226.
Serre, D., Langaney, A., Chech, M., Teschler-Nicola, M., Paunovic, M., Mennecier, P., Hofreiter, M., Possnert, G., Pääbo, S., 2004. No evidence of Neandertal mtDNA contribution to early modern humans. PLoS Biol. 2, 313–317.
Sherry, S.T., Rogers, A.R., Harpending, H., Soodyall, H., Jenkins, T., Stoneking, M., 1994. Mismatch distribution of mtDNA reveal recent human population expansions. Hum. Biol. 66, 761–775.
Soffer, O., 2004. Recovering perishable technologies through use wear on tools: Preliminary evidence for Upper Paleolithic weaving and net making. Curr. Anthropol. 45, 407–413.
Spuhler, J.N., 1989. Evolution of mitochondrial DNA in human and other organisms. Am. J. Hum. Biol. 1, 509–528.
Stefansson, H., Helgason, A., Steinthorsdottir, G.T.V., Masson, G., Bernard, J., Baker, A., Jonasdottir, A., Ingason, A., Gudnadottir, V.G., Desnica, N., Hicks, A., Gylfason, A., Gudbjartsson, D.F., Jonsdottir, G.M., Sainz, J., Agnarsson, K., Birgisdottir, B., Ghosh, S., Olafsdottir, A., Cazier, J.-B., Kristjansson, K., Frigge, M.L., Thorgeirsson, T.E., Gulcher, J.R., Kong, A., Stefansson, K., 2005. A common inversion under selection in Europeans. Nat. Genet. 37, 129–137.
Stiner, M.C., Munro, N.D., Surovell, T.A., 2000. The tortoise and the hare: Small-game use, the broad-spectrum revolution, and Paleolithic demography. Curr. Anthropol. 41, 39–73.
Stringer, C., 2002. Modern human origins: Progress and prospects. Phil. Trans. R. Soc. Lond. B 357, 563–579.
Stringer, C.B., Andrews, P., 1988. Genetic and fossil evidence for the origin of modern humans. Science 239, 1263–1268.
Stringer, C.B., Bräuer, G., 1994. Methods, misreading and bias. Am. Anthropol. 96, 416–424.
Tattersall, I., Schwartz, J.H., 1999. Hominids and hybrids: The place of Neanderthals in human evolution. Proc. Natl. Acad. Sci. U.S.A. 96, 7117–7119.
Templeton, A., 1993. The “Eve” hypothesis: a genetic critique and reanalysis. Am. Anthropol. 95, 51–72.
Templeton, A.R., 2002. Out of Africa again and again. Nature 416, 45–51.
Tishkoff, S.A., Dietzsch, E., Seed, W., Pakstis, A.J., Kidd, J.R., Cheung, K., Bonné-Tamir, B., Santachiara-Benerecetti, A.S., Moral, P., Krings, M., Pääbo, S., Watson, E., Risch, N., Jenkins, T., Kidd, K.K., 1996. Global patterns of disequilibrium at the CD4 locus and modern human origins. Science 271, 1380–1387.
Trinkaus, E., 2005. Early modern humans. Ann. Rev. Anthropol. 34, 207–230.
Trinkaus, E., Milota, S., Rodrigo, R., Mircea, G., Moldovan, O., 2003. Early modern human cranial remains from the Peştera cu Oase, Romania. J. Hum. Evol. 45, 245–253.
Vallender, E.J., Lahn, B.T., 2004. Positive selection on the human genome. Hum. Mol. Genet. 13, R245–R254.
Vigilant, L., Stoneking, M., Harpending, H., Hawkes, K., Wilson, A.C., 1991. African populations and the evolution of human mitochondrial DNA. Science 253, 1503–1507.
Wall, J.D., 2000. Detecting ancient admixture in humans using sequence polymorphism data. Genetics 154, 1271–1279.
Wallace, D.C., 2005a. The mitochondrial genome in human adaptive radiation and disease: on the road to therapeutics and performance enhancement. Gene 354, 169–180.
Wallace, D.C., 2005b. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: A dawn for evolutionary medicine. Ann. Rev. Genet. 39, 359–407.
Wallace, D.C., Lott, M.T., 2002. Mitochondrial genes in degenerative diseases, cancer, and aging. In: Rimoin, D.L., Connor, J.M., Pyeritz, R.E., Korf, B.R. (Eds.), Emery and Rimoin’s Principles and Practice of Medical. Churchill Livingstone, London, pp. 299–409.
Wallace, D.C., Brown, M.D., Lott, M.T., 1999. Mitochondrial DNA variation in human evolution and disease. Gene 238, 211–230.
Wallace, D.C., Lott, M.T., Brown, M.D., Kerstann, K., 2001. Mitochondria and neuro-opthalmological diseases. In: Scriver, C.R., Beaudet, A.L., Sly, W.S., Valle, D. (Eds.), The Metabolic and Molecular Basis of Inherited Disease, Vol. 2. McGraw-Hill, New York, pp. 2425–2512.
Weaver, T.D., Roseman, C.C., 2005. Ancient DNA, late Neandertal survival, and modern-human-Neandertal genetic admixture. Curr. Anthropol. 46, 677–683.
Williamson, S.H., Hernandez, R., Fledel-Alon, A., Zhu, L., Nielsen, R., Bustamante, C.D., 2005. Simultaneous inference of selection and population growth from patterns of variation in the human genome. Proc. Natl. Acad. Sci. U.S.A. 102, 7882–7887.
Wills, C., 1995. When did Eve live? An evolutionary detective story. Evolution 49, 593–607.
Wilson, A.C., Cann, R.L., 1992. The recent African genesis of humans. Sci. Am. 266, 68–73.
Wise, C.A., Sraml, M., Rubinsztein, D.C., Easteal, S., 1997. Comparative nuclear and mitochondrial genome diversity in humans and chimpanzees. Mol. Biol. Evol. 14, 707–716.
Wise, C.A., Sraml, M., Easteal, S., 1998. Departure from neutrality at the mitochondrial NADH dehydrogenase subunit 2 gene in humans, but not in chimpanzees. Genetics 148, 409–421.
Wolpoff, M.H., Hawks, J., Frayer, D.W., Hunley, K., 2001. Modern human ancestry at the peripheries: a test of the replacement theory. Science 291, 293–297.
Yellen, J.E., Brooks, A., Cornelissen, E., Mehlman, M., Stewart, K., 1995. A Middle Stone Age worked bone industry from Katanda, Upper Semiliki Valley, Zaire. Science 268, 553–556.
Zhivotovsky, L.A., Bennett, L., Bowcock, A.M., Feldman, M.W., 2000. Human population expansion and microsatellite variation. Mol. Biol. Evol. 17, 757–767.
Zhivotovsky, L.A., Rosenberg, N.A., Feldman, M.W., 2003. Features of evolution and expansion of modern humans, inferred from genomewide microsatellite markers. Am. J. Hum. Genet. 72, 1171–1186.
Zhu, X., Smith, M.A., Perry, G., Aliev, G., 2004. Mitochondrial failures in Alzheimer’s disease. Am. J. Alzheimer’s Dis. Other Dementias 19, 345–352.
Zischler, H., Geisert, H., von Haeseler, A., Pääbo, S., 1995. A nuclear “fossil” of the mitochondrial D-loop and the origin of modern humans. Nature 378, 489–492.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer
About this chapter
Cite this chapter
Hawks, J. (2006). Selection Selection on mitochondrial DNA and the Neanderthal problem. In: Hublin, JJ., Harvati, K., Harrison, T. (eds) Neanderthals Revisited: New Approaches and Perspectives. Vertebrate Paleobiology and Paleoanthropology. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-5121-0_12
Download citation
DOI: https://doi.org/10.1007/978-1-4020-5121-0_12
Publisher Name: Springer, Dordrecht
Print ISBN: 978-1-4020-5120-3
Online ISBN: 978-1-4020-5121-0
eBook Packages: Earth and Environmental ScienceEarth and Environmental Science (R0)