Evolution of the Human Genome: Adaptive Changes

Abstract

The study of human evolution is of interest to many both for the potential it has to improve our understanding of heritable disease, as well as for the possibility of illuminating evidence for adaptations that may help to tell the story of our origin. But uncovering evidence of positive selection at the genetic level has been a challenge. It remains unclear how much of the human genome has been affected by positive selection, what the main mechanism of selection is, and what types of patterns we should be looking for to identify adaptations. With whole‐genome sequencing and high performance computation, we are quickly shifting to a field in which data is no longer a limiting factor. Here we will discuss the progress that has been made towards these ends, explore the best examples of human‐specific adaptations to date, and discuss the implications of these findings within the context of classical population genetic theory.

Key Concepts:

  • An abundance of genomic data allows for a genotype‐first approach to discover selection in humans.

  • Ancient hominin genomic sequences provide a nearer outgroup to humans than chimpanzee, and therefore can help elucidate selective targets in humans.

  • Hard sweeps may have been rare in human evolution, whereas soft sweeps are a much more likely mechanism of selection.

  • The genomic signatures of sweeps, background selection, and demography all look similar and can be difficult to distinguish.

  • Genomic scans for selection make use of various signatures of selection and they rarely identify overlapping targets.

  • More accurate modelling of selection in humans is needed to find true signals of selection.

Keywords: ancient hominin genomes; demography; genome scans; hitchhiking; human adaptation; human evolution; selective sweeps; soft sweeps

Figure 1.

Phylogeny of the great apes and approximate divergence times. Branches are not drawn to scale. The Neanderthal and Denisova branches are intentionally truncated to indicate extinct versus extant.

Figure 2.

The hitchhiking effect. Each grey or red line represents a chromosome from a single individual. (a) A beneficial mutation arises in the population and is closely linked to a neutral allele. (b) As the mutation rises in frequency, it brings with it linked neutral alleles. Only alleles that recombine onto the beneficial haplotype are not lost from the sample. (c) After the sweep is completed the closely linked allele is fixed. Thus only high frequency alleles that have ‘hitchhiked’ with the beneficial mutation are visible as variation within the sample, and subsequent new mutations appear as rare variants.

Figure 3.

A comparison of the site frequency spectrum under equilibrium and nonequilibrium conditions. Plots are based on simulation of a 5 Kb region using either msms (a–c) or sfscode (d) with human‐like parameters (effective population size of 10 000, per site mutation rate of 2.35×10−8, and per site recombination rate of 2.56×10−8). Counts on the y‐axis are the total number of mutations based on 1000 iterations. (a) Equilibrium neutral population. (b) 1% positive selection at a single locus. (c) Nonequilibrium neutral population. Demographic parameters include an 80% reduction in population size 50 Kya, with an exponential growth of 5% for the last 1000 years. (d) Background selection, with 80% of sites experiencing negative selection (coefficient of selection=0.01). It is apparent from this figure that both demography and selection greatly reduce the number of mutations compared to neutrality.

close

References

Allison AC (1954) Protection afforded by sickle‐cell trait against subtertian malareal infection. British Medical Journal 1: 290–294.

Baudat F, Buard J, Grey C et al. (2010) PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327: 836–840.

Beall CM, Cavalleri GL, Deng L et al. (2010) Natural selection on EPAS1 (HIF2alpha) associated with low hemoglobin concentration in Tibetan highlanders. Proceedings of the National Academy of Sciences of the USA 107: 11459–11464.

Cai JJ, Macpherson JM, Sella G and Petrov DA (2009) Pervasive hitchhiking at coding and regulatory sites in humans. PLoS Genetics 5: e1000336.

Coop G, Bullaughey K, Luca F and Przeworski M (2008) The timing of selection at the human FOXP2 gene. Molecular Biology and Evolution 25: 1257–1259.

Crisci JL, Poh YP, Bean A, Simkin A and Jensen JD (2012) Recent progress in polymorphism‐based population genetic inference. The Journal of Heredity 103: 287–296

Crisci JL, Wong A, Good JM and Jensen JD (2011) On characterizing adaptive events unique to modern humans. Genome Biology and Evolution 3: 791–798.

Durbin RM, Altshuler DL, Abecasis G et al. (2010) A map of human genome variation from population‐scale sequencing. Nature 467: 1061–1073.

Elvin SJ, Williamson ED, Scott JC et al. (2004) Evolutionary genetics: ambiguous role of CCR5 in Y. pestis infection. Nature 430: 417.

Enard W, Przeworski M, Fisher SE et al. (2002) Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418: 869–872.

Feinberg AP and Irizarry RA (2010) Stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease. Proceedings of the National Academy of Sciences of the USA 107(suppl 1): 1757–1764.

Fisher SE, Vargha‐Khadem F, Watkins KE et al. (1998) Localisation of a gene implicated in a severe speech and language disorder. Nature Genetics 18: 168–170.

Galvani AP and Novembre J (2005) The evolutionary history of the CCR5‐Delta32 HIV‐resistance mutation. Microbes and Infection 7: 302–309.

Geoghegan JL and Spencer HG (2011) Population‐epigenetic models of selection. Theoretical Population Biology 83: 232–242.

Gillespie J (1977) Natural selection for variances in offspring numbers: a new evolutionary principle. American Naturalist 111: 1010–1014.

Green RE, Krause J, Briggs AW et al. (2010) A draft sequence of the Neandertal genome. Science 328: 710–722.

Hermisson J and Pennings PS (2005) Soft sweeps: molecular population genetics of adaptation from standing genetic variation. Genetics 169: 2335–2352.

Hernandez RD, Kelley JL, Elyashiv E et al. (2011) Classic selective sweeps were rare in recent human evolution. Science 331: 920–924.

International Human Genome Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921.

Jablonka E, Lamb MJ and Avital E (1998) ‘Lamarckian’ mechanisms in darwinian evolution. Trends in Ecology & Evolution 13: 206–210.

Kaplan NL, Hudson RR and Langley CH (1989) The ‘hitchhiking effect’ revisited. Genetics 123: 887–899.

Kim YH and Nielsen R (2004) Linkage disequilibrium as a signature of selective sweeps. Genetics 167: 1513–1524.

Kimura M (1968) Evolutionary rate at the molecular level. Nature 217: 624–626.

Kimura M (1983) The Neutral Theory of Evolution. Cambridge: Cambridge University Press.

Krause J, Lalueza‐Fox C, Orlando L et al. (2007) The derived FOXP2 variant of modern humans was shared with Neandertals. Current Biology 17: 1908–1912.

Kwiatkowski DP (2005) How malaria has affected the human genome and what human genetics can teach us about malaria. American Journal of Human Genetics 77: 171–192.

Lai CS, Fisher SE, Hurst JA, Vargah‐Khadem F and Monaco AP (2001) A forkhead‐domain gene is mutated in a severe speech and language disorder. Nature 413: 519–523.

Lalani AS, Masters J, Zeng W et al. (1999) Use of chemokine receptors by poxviruses. Science 286: 1968–1971.

Locke DP, Hillier LW, Warren WC et al. (2011) Comparative and demographic analysis of orang‐utan genomes. Nature 469: 529–533.

Maynard Smith JM and Haigh J (1974) The hitch‐hiking effect of a favourable gene. Genetical Research 23: 23–35.

McDonald JH and Kreitman M (1991) Adaptive protein evolution at the Adh locus in Drosophila. Nature 351: 652–654.

Mecsas J, Franklin G, Kuziel W and Brubaker RR (2004) Evolutionary genetics: CCR5 mutation and plague protection. Nature 427: 606.

Miller LH, Mason SJ, Dvorak JA, McGinnis MH and Rothman IK (1975) Erythrocyte receptors for (Plasmodium knowlesi) malaria: Duffy blood group determinants. Science 189: 561–562.

Molaro A, Hodges E, Fang F et al. (2011) Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates. Cell 146: 1029–1041.

Nei M and Gojobori T (1986) Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Molecular Biology and Evolution 3: 418–426.

Ohta T (1973) Slightly deleterious mutant substitutions in evolution. Nature 246: 96–97.

Orr HA and Betancourt AJ (2001) Haldane's sieve and adaptation from the standing genetic variation. Genetics 157: 875–884.

Patel SA and Simon MC (2008) Biology of hypoxia‐inducible factor‐2alpha in development and disease. Cell Death and Differentiation 15: 628–634.

Peng Y, Yang Z, Zhang H et al. (2011) Genetic variations in Tibetan populations and high‐altitude adaptation at the Himalayas. Molecular Biology and Evolution 28: 1075–1081.

Pennings PS and Hermisson J (2006) Soft sweeps III: the signature of positive selection from recurrent mutation. PLoS genetics 2(12): e186.

Przeworski M (2002) The signature of positive selection at randomly chosen loci. Genetics 160: 1179–1189.

Przewoski M, Coop G and Wall JD (2005) The signature of positive selection on standing genetic variation. Evolution 59: 2312–2323.

Reich D, Green RE, Kircher M et al. (2010) Genetic history of an archaic hominin group from Denisova cave in Siberia. Nature 468: 1053–1060.

Sabeti PC, Varilly P, Fry B et al. (2007) Genome‐wide detection and characterization of positive selection in human populations. Nature 449: 913–918.

Samson M, Libert F, Doranz BJ et al. (1996) Resistance to HIV‐1 infection in caucasian individuals bearing mutant alleles of the CCR‐5 chemokine receptor gene. Nature 382: 722–725.

Scally A, Dutheil JY, Hillier LW et al. (2012) Insights into hominid evolution from the gorilla genome sequence. Nature 483: 169–175.

Ségurel L, Leffler EM and Przeworski M (2011) The case of the fickle fingers: how the PRDM9 zinc finger protein specifies meiotic recombination hotspots in humans. PLoS Biology 9: e1001211.

Stephens JC, Reich DE, Goldstein DB et al. (1998) Dating the origin of the CCR5‐Delta32 AIDS‐resistance allele by the coalescence of haplotypes. American Journal of Human Genetics 62: 1507–1515.

Swallow DM (2003) Genetics of lactase persistence and lactose intolerance. Annual Review of Genetics 37: 197–219.

The Chimpanzee Sequencing and Analysis Consortium (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437: 69–87.

Thornton KR, Jensen JD, Becquet C and Andolfatto P (2007) Progress and prospects in mapping recent selection in the genome. Heredity 98: 340–348.

Tishkoff SA, Reed FA, Ranciaro A et al. (2006) Convergent adaptation of human lactase persistence in Africa and Europe. Nature Genetics 39: 31–40.

Turelli M and Barton NH (1990) Dynamics of polygenic characters under selection. Theoretical Population Biology 38: 1–57.

Venter JC, Adams MD, Myers EW et al. (2001) The sequence of the human genome. Science 291: 1304–1351.

Xu S, Li S, Yang Y et al. (2011) A genome‐wide search for signals of high‐altitude adaptation in Tibetans. Molecular Biology and Evolution 28: 1003–1011.

Yi X, Liang Y, Huerta‐Sanchez E et al. (2010) Sequencing of 50 human exomes reveals adaptation to high altitude. Science 329: 75–78.

Further Reading

Eyre‐Walker A (2006) The genomic rate of adaptive evolution. Trends in Ecology & Evolution 21: 569–575.

Jensen JD (2009) On reconciling single and recurrent hitchhiking models. Genome Biology and Evolution 1: 320–244.

Nielsen R (2005) Molecular signatures of natural selection. Annual Reviews Genetics 39: 197–218.

Ohta T (2011) Near‐neutrality, robustness, and epigenetics. Genome Biology and Evolution 3: 1034–1038.

Pool JE, Hellmann I, Jensen JD and Nielsen R (2010) Population genetic inference from genomic sequence variation. Genome Research 20: 291–300.

Pritchard JK and Pickrell JK (2010) The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Current Biology 20: 208–215.

Stephan W (2010) Genetic hitchhiking versus background selection: the controversy and its implications. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 365: 1245–1253.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Crisci, Jessica L, and Jensen, Jeffrey D(May 2012) Evolution of the Human Genome: Adaptive Changes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023987]