Multiple Instances of Ancient Balancing Selection Shared Between Humans and Chimpanzees
Balancing Humans with Apes
Shared ancestral polymorphisms between species tend to be relatively rare, and studies of trans-species polymorphisms have focused on just a few regions known for balancing selection. Leffler et al. (p. 1578, published online 14 February) performed genome-wide scans among humans and great apes and found shared polymorphisms between chimps and humans. Many of the identified variants seem to be associated with genes involved in pathogen response or defense, suggesting that this widespread balancing selection may reflect the ongoing arms race between pathogens and hosts.
Abstract
Instances in which natural selection maintains genetic variation in a population over millions of years are thought to be extremely rare. We conducted a genome-wide scan for long-lived balancing selection by looking for combinations of SNPs shared between humans and chimpanzees. In addition to the major histocompatibility complex, we identified 125 regions in which the same haplotypes are segregating in the two species, all but two of which are noncoding. In six cases, there is evidence for an ancestral polymorphism that persisted to the present in humans and chimpanzees. Regions with shared haplotypes are significantly enriched for membrane glycoproteins, and a similar trend is seen among shared coding polymorphisms. These findings indicate that ancient balancing selection has shaped human variation and point to genes involved in host-pathogen interactions as common targets.
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References
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References and Notes
1
Hedrick P. W., Population genetics of malaria resistance in humans. Heredity (Edinb.) 107, 283 (2011).
2
Reid D. G., Natural selection for apostasy and crypsis acting on the shell colour polymorphism of a mangrove snail, Littoraria filosa (Sowerby) (Gastropoda: Littorinidae). Biol. J. Linn. Soc. Lond. 30, 1 (1987).
3
Gigord L. D., Macnair M. R., Smithson A., Negative frequency-dependent selection maintains a dramatic flower color polymorphism in the rewardless orchid Dactylorhiza sambucina (L.) Soo. Proc. Natl. Acad. Sci. U.S.A. 98, 6253 (2001).
4
Stahl E. A., Dwyer G., Mauricio R., Kreitman M., Bergelson J., Dynamics of disease resistance polymorphism at the Rpm1 locus of Arabidopsis. Nature 400, 667 (1999).
5
Wright S., The distribution of self-sterility alleles in populations. Genetics 24, 538 (1939).
6
Hiwatashi T., et al., An explicit signature of balancing selection for color-vision variation in new world monkeys. Mol. Biol. Evol. 27, 453 (2010).
7
Heliconious Genome Consortium, Butterfly genome reveals promiscuous exchange of mimicry adaptations among species. Nature 487, 94 (2012).
8
Ghosh R., Andersen E. C., Shapiro J. A., Gerke J. P., Kruglyak L., Natural variation in a chloride channel subunit confers avermectin resistance in C. elegans. Science 335, 574 (2012).
9
B. Charlesworth, D. Charlesworth, Elements of Evolutionary Genetics (Roberts and Company, Greenwood Village, CO, 2010).
10
T. Dobzhansky, Genetics of the Evolutionary Process (Columbia Univ. Press, New York, 1970).
11
R. C. Lewontin, The Genetic Basis of Evolutionary Change (Columbia Univ. Press, New York, 1974).
12
J. H. Gillespie, The Causes of Molecular Evolution (Oxford Univ. Press, Oxford, 1991).
13
Hudson R. R., Kaplan N. L., The coalescent process in models with selection and recombination. Genetics 120, 831 (1988).
14
Charlesworth D., Balancing selection and its effects on sequences in nearby genome regions. PLoS Genet. 2, e64 (2006).
15
Wiuf C., Zhao K., Innan H., Nordborg M., The probability and chromosomal extent of trans-specific polymorphism. Genetics 168, 2363 (2004).
16
Materials and methods are available as supplementary materials on Science Online.
17
Klein J., Satta Y., O’HUigin C., Takahata N., The molecular descent of the major histocompatibility complex. Annu. Rev. Immunol. 11, 269 (1993).
18
Ségurel L., et al., The ABO blood group is a trans-species polymorphism in primates. Proc. Natl. Acad. Sci. U.S.A. 109, 18493 (2012).
19
Bubb K. L., et al., Scan of human genome reveals no new Loci under ancient balancing selection. Genetics 173, 2165 (2006).
20
The 1000 Genomes Project Consortium, A map of human genome variation from population-scale sequencing. Nature 467, 1061 (2010).
21
Auton A., et al., A fine-scale chimpanzee genetic map from population sequencing. Science 336, 193 (2012).
22
Patterson N., Richter D. J., Gnerre S., Lander E. S., Reich D., Genetic evidence for complex speciation of humans and chimpanzees. Nature 441, 1103 (2006).
23
Hodgkinson A., Eyre-Walker A., Variation in the mutation rate across mammalian genomes. Nat. Rev. Genet. 12, 756 (2011).
24
Franchini M., Capra F., Targher G., Montagnana M., Lippi G., Relationship between ABO blood group and von Willebrand factor levels: From biology to clinical implications. Thromb. J. 5, 14 (2007).
25
Gieger C., et al., New gene functions in megakaryopoiesis and platelet formation. Nature 480, 201 (2011).
26
Ko W. Y., et al., Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations. Am. J. Hum. Genet. 88, 741 (2011).
27
Kudo S., Fukuda M., Identification of a novel human glycophorin, glycophorin E, by isolation of genomic clones and complementary DNA clones utilizing polymerase chain reaction. J. Biol. Chem. 265, 1102 (1990).
28
Nagakubo D., et al., A high endothelial venule secretory protein, mac25/angiomodulin, interacts with multiple high endothelial venule-associated molecules including chemokines. J. Immunol. 171, 553 (2003).
29
Monnier J., Samson M., Cytokine properties of prokineticins. FEBS J. 275, 4014 (2008).
30
Videira P. A., et al., Surface alpha 2-3- and α2-6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis. Glycoconj. J. 25, 259 (2008).
31
Priatel J. J., et al., The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by modulating O-glycan biosynthesis. Immunity 12, 273 (2000).
32
Johnsen J. M., et al., Selection on cis-regulatory variation at B4galnt2 and its influence on von Willebrand factor in house mice. Mol. Biol. Evol. 26, 567 (2009).
33
Gagneux P., Varki A., Evolutionary considerations in relating oligosaccharide diversity to biological function. Glycobiology 9, 747 (1999).
34
Olofsson S., Bergström T., Glycoconjugate glycans as viral receptors. Ann. Med. 37, 154 (2005).
35
Day C. J., Semchenko E. A., Korolik V., Glycoconjugates play a key role in campylobacter jejuni infection: Interactions between host and pathogen. Front. Cell. Infect. Microbiol. 2, 9 (2012).
36
Ruwende C., et al., Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 376, 246 (1995).
37
Tellier A., Brown J. K., Stability of genetic polymorphism in host-parasite interactions. Proc. Biol. Sci. 274, 809 (2007).
38
Takahata N., A simple genealogical structure of strongly balanced allelic lines and trans-species evolution of polymorphism. Proc. Natl. Acad. Sci. U.S.A. 87, 2419 (1990).
39
Chimpanzee Sequencing and Analysis Consortium, Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69 (2005).
40
Zeller T., et al., Genetics and beyond—The transcriptome of human monocytes and disease susceptibility. PLoS ONE 5, e10693 (2010).
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Science
Volume 339 | Issue 6127
29 March 2013
29 March 2013
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Copyright © 2013, American Association for the Advancement of Science.
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Submission history
Received: 13 December 2012
Accepted: 1 February 2013
Published in print: 29 March 2013
Acknowledgments
We thank D. Conrad, Y. Lee, M. Nobrega, J. Pickrell, and H. Shim as well as A. Kermany, A. Venkat, and other members of the PPS labs for helpful discussions; I. Aneas, M. Çalışkan, M. Nobrega, and C. Ober for their assistance with experiments; and G. Coop for discussions and comments on an earlier version of this manuscript. E.M.L. was supported in part by NIH training grant T32 GM007197. This work was supported by NIH HG005226 to J.D.W.; Israel Science Foundation grant 1492/10 to G.S.; a Wolfson Royal Society Merit Award, a Wellcome Trust Senior Investigator award (095552/Z/11/Z), and Wellcome Trust grants 090532/Z/09/Z and 075491/Z/04/B to P.D.; Wellcome Trust grant 086084/Z/08/Z to G.M.; and NIH grant GM72861 to M.P. M.P. is a Howard Hughes Medical Institute Early Career Scientist. The data set of shared SNPs is available from http://przeworski.uchicago.edu/wordpress/?page_id=20. Data from the validation experiment are available from GenBank under accession nos. KC541701 to KC542146. The biological material obtained from the San Diego Zoo and used in this study is subject to a materials tranfer agreement.
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