Characteristics of neutral and deleterious protein-coding variation among individuals and populations

American Journal of Human Genetics

Volumn 95, Issue 4, 2014, Pages 421-436

  Fu, Wenqing ^a   Gittelman, Rachel M ^a   Bamshad, Michael J ^a,b   Akey, Joshua M ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN VARIANT; PROTEIN;

AFRICAN AMERICAN; ALLELE; ARTICLE; EUROPEAN AMERICAN; EXOME; FEMALE; GENE IDENTIFICATION; GENE MUTATION; GENE SEQUENCE; GENETIC CODE; GENETIC VARIABILITY; GENOME ANALYSIS; GENOTYPE; HUMAN; MALE; NATURAL SELECTION; POPULATION; POPULATION GENETICS; PRIORITY JOURNAL; PROTEIN CODING VARIATION; PROTEIN POLYMORPHISM; SEQUENCE ALIGNMENT; SEQUENCE ANALYSIS; SIMULATION; SINGLE NUCLEOTIDE POLYMORPHISM; AFRICA; BLACK PERSON; CAUCASIAN; ETHNOLOGY; EUROPE; EXON; GENETIC DRIFT; GENETIC SELECTION; GENETICS; HUMAN GENOME; MOLECULAR EVOLUTION; THEORETICAL MODEL;

AFRICA; AFRICAN CONTINENTAL ANCESTRY GROUP; EUROPE; EUROPEAN CONTINENTAL ANCESTRY GROUP; EVOLUTION, MOLECULAR; EXOME; EXONS; GENETIC DRIFT; GENETICS, POPULATION; GENOME, HUMAN; HUMANS; MODELS, THEORETICAL; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEINS; SELECTION, GENETIC;

EID: 84921818763     PISSN: 00029297     EISSN: 15376605     Source Type: Journal    
DOI: 10.1016/j.ajhg.2014.09.006     Document Type: Article

References (66)

1. The URLs for data presented herein are as follows: 1000 Genomes, http://www.1000genomes.org/
2. BEDOPS, https://code.google.com/p/bedops/
3. Ensembl Genome Browser, http://useast.ensembl.org/index.html
4. mafTools, https://github.com/dentearl/mafTools
5. NHLBI Exome Sequencing Project (ESP). Exome Variant Server. http://evs.gs.washington.edu/EVS/
6. PHAST, http://compgen.bscb.cornell.edu/phast/
7. PhyloPNH, http://akeylab.gs.washington.edu/downloads.shtml
8. SFS-CODE, http://sfscode.sourceforge.net/SFS-CODE/index/index.html
9. UCSC Genome Browser, http://genome.ucsc.edu
10. Haldane, J.B.S. (1937). The effect of variation on fitness. Am. Nat. 71, 337-349.
11. Crow, J.F. (1970). Genetic Loads and the Cost of Natural Selection. In Mathematical Topics in Population Genetics, K.-i. Kojima, ed. (New York: Springer-Verlag), pp. 128-177.
12. Crow, J.F. (2000). The origins, patterns and implications of human spontaneous mutation. Nat. Rev. Genet. 1, 40-47.
13. Gavrilov, L.A., Gavrilova, N.S., Kroutko, V.N., Evdokushkina, G.N., Semyonova, V.G., Gavrilova, A.L., Lapshin, E.V., Evdokushkina, N.N., and Kushnareva, Y.E. (1997). Mutation load and human longevity. Mutat. Res. 377, 61-62.
14. Lynch, M. (2010). Rate, molecular spectrum, and consequences of human mutation. Proc. Natl. Acad. Sci. USA 107, 961-968.
15. Kimura, M., Maruyama, T., and Crow, J.F. (1963). The Mutation Load in Small Populations. Genetics 48, 1303-1312.
16. Ohta, T. (1973). Slightly deleterious mutant substitutions in evolution. Nature 246, 96-98.
17. Peischl, S., Dupanloup, I., Kirkpatrick, M., and Excoffier, L. (2013). On the accumulation of deleterious mutations during range expansions. Mol. Ecol. 22, 5972-5982.
18. Abecasis, G.R., Auton, A., Brooks, L.D., DePristo, M.A., Durbin, R.M., Handsaker, R.E., Kang, H.M., Marth, G.T., and McVean, G.A.; 1000 Genomes Project Consortium (2012). An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56-65.
19. Lohmueller, K.E., Indap, A.R., Schmidt, S., Boyko, A.R., Hernandez, R.D., Hubisz, M.J., Sninsky, J.J., White, T.J., Sunyaev, S.R., Nielsen, R., et al. (2008). Proportionally more deleterious genetic variation in European than in African populations. Nature 451, 994-997.
20. Simons, Y.B., Turchin, M.C., Pritchard, J.K., and Sella, G. (2014). The deleterious mutation load is insensitive to recent population history. Nat. Genet. 46, 220-224.
21. Tennessen, J.A., Bigham, A.W., O'Connor, T.D., Fu,W., Kenny, E.E., Gravel, S., McGee, S., Do, R., Liu, X., Jun, G., et al.; Broad GO; Seattle GO; NHLBI Exome Sequencing Project (2012). Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 337, 64-69.
22. Hodgkinson, A., Casals, F., Idaghdour, Y., Grenier, J.C., Hernandez, R.D., and Awadalla, P. (2013). Selective constraint, background selection, and mutation accumulation variability within and between human populations. BMC Genomics 14, 495.
23. Fu,W., O'Connor, T.D., Jun, G., Kang, H.M., Abecasis, G., Leal, S.M., Gabriel, S., Rieder, M.J., Altshuler, D., Shendure, J., et al.; NHLBI Exome Sequencing Project (2013). Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature 493, 216-220.
24. Kidd, J.M., Gravel, S., Byrnes, J., Moreno-Estrada, A., Musharoff, S., Bryc, K., Degenhardt, J.D., Brisbin, A., Sheth, V., Chen, R., et al. (2012). Population genetic inference from personal genome data: impact of ancestry and admixture on human genomic variation. Am. J. Hum. Genet. 91, 660-671.
25. Subramanian, S. (2012). The abundance of deleterious polymorphisms in humans. Genetics 190, 1579-1583.
26. Casals, F., Hodgkinson, A., Hussin, J., Idaghdour, Y., Bruat, V., de Maillard, T., Grenier, J.C., Gbeha, E., Hamdan, F.F., Girard, S., et al. (2013). Whole-exome sequencing reveals a rapid change in the frequency of rare functional variants in a founding population of humans. PLoS Genet. 9, e1003815.
27. Szpiech, Z.A., Xu, J., Pemberton, T.J., Peng, W., Zöllner, S., Rosenberg, N.A., and Li, J.Z. (2013). Long runs of homozygosity are enriched for deleterious variation. Am. J. Hum. Genet. 93, 90-102.
28. Do, R., Balick, D., Li, H., Adzhubei, I., Sunyaev, S., and Reich, D. (2014). No evidence that natural selection has been less effective at removing deleterious mutations in Europeans than in West Africans. arXiv, arXiv:1402.4896, http://arxiv.org/abs/1402.4896.
29. Abecasis, G.R., Altshuler, D., Auton, A., Brooks, L.D., Durbin, R.M., Gibbs, R.A., Hurles, M.E., and McVean, G.A.; 1000 Genomes Project Consortium (2010). A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073.
30. Hernandez, R.D., Williamson, S.H., and Bustamante, C.D. (2007). Context dependence, ancestral misidentification, and spurious signatures of natural selection. Mol. Biol. Evol. 24, 1792-1800.
31. Hwang, D.G., and Green, P. (2004). Bayesian Markov chain Monte Carlo sequence analysis reveals varying neutral substitution patterns in mammalian evolution. Proc. Natl. Acad. Sci. USA 101, 13994-14001.
32. Pennacchio, L.A., Olivier, M., Hubacek, J.A., Cohen, J.C., Cox, D.R., Fruchart, J.C., Krauss, R.M., and Rubin, E.M. (2001). An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294, 169-173.
33. Boffelli, D., McAuliffe, J., Ovcharenko, D., Lewis, K.D., Ovcharenko, I., Pachter, L., and Rubin, E.M. (2003). Phylogenetic shadowing of primate sequences to find functional regions of the human genome. Science 299, 1391-1394.
34. Pollard, K.S., Hubisz, M.J., Rosenbloom, K.R., and Siepel, A. (2010). Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res. 20, 110-121.
35. Neph, S., Kuehn, M.S., Reynolds, A.P., Haugen, E., Thurman, R.E., Johnson, A.K., Rynes, E., Maurano, M.T., Vierstra, J., Thomas, S., et al. (2012). BEDOPS: high-performance genomic feature operations. Bioinformatics 28, 1919-1920.
36. Hernandez, R.D. (2008). A flexible forward simulator for populations subject to selection and demography. Bioinformatics 24, 2786-2787.
37. Gravel, S., Henn, B.M., Gutenkunst, R.N., Indap, A.R., Marth, G.T., Clark, A.G., Yu, F., Gibbs, R.A., and Bustamante, C.D.; 1000 Genomes Project (2011). Demographic history and rare allele sharing among human populations. Proc. Natl. Acad. Sci. USA 108, 11983-11988.
38. Keinan, A., Mullikin, J.C., Patterson, N., and Reich, D. (2007). Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans. Nat. Genet. 39, 1251-1255.
39. Boyko, A.R., Williamson, S.H., Indap, A.R., Degenhardt, J.D., Hernandez, R.D., Lohmueller, K.E., Adams, M.D., Schmidt, S., Sninsky, J.J., Sunyaev, S.R., et al. (2008). Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genet. 4, e1000083.
40. Morton, N.E., Crow, J.F., and Muller, H.J. (1956). An Estimate of the Mutational Damage in Man from Data on Consanguineous Marriages. Proc. Natl. Acad. Sci. USA 42, 855-863.
41. Crow, J.F. (1958). Some possibilities for measuring selection intensities in man. Hum. Biol. 30, 1-13.
42. Muller, H.J. (1950). Our load of mutations. Am. J. Hum. Genet. 2, 111-176.
43. Nickerson, D.A., Taylor, S.L., Weiss, K.M., Clark, A.G., Hutchinson, R.G., Stengard, J., Salomaa, V., Vartiainen, E., Boerwinkle, E., and Sing, C.F. (1998). DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nat. Genet. 19, 233-240.
44. Campbell, M.C., and Tishkoff, S.A. (2008). African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu. Rev. Genomics Hum. Genet. 9, 403-433.
45. Kircher, M.,Witten, D.M., Jain, P., O'Roak, B.J., Cooper, G.M., and Shendure, J. (2014). A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet. 46, 310-315.
46. Chun, S., and Fay, J.C. (2009). Identification of deleterious mutations within three human genomes. Genome Res. 19, 1553-1561.
47. Davydov, E.V., Goode, D.L., Sirota, M., Cooper, G.M., Sidow, A., and Batzoglou, S. (2010). Identifying a high fraction of the human genome to be under selective constraint using GERP. PLoS Comput. Biol. 6, e1001025.
48. Adzhubei, I.A., Schmidt, S., Peshkin, L., Ramensky, V.E., Gerasimova, A., Bork, P., Kondrashov, A.S., and Sunyaev, S.R. (2010). A method and server for predicting damaging missense mutations. Nat. Methods 7, 248-249.
49. Schwarz, J.M., Rödelsperger, C., Schuelke, M., and Seelow, D. (2010). MutationTaster evaluates disease-causing potential of sequence alterations. Nat. Methods 7, 575-576.
50. Kumar, P., Henikoff, S., and Ng, P.C. (2009). Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat. Protoc. 4, 1073-1081.
51. Lachance, J., Vernot, B., Elbers, C.C., Ferwerda, B., Froment, A., Bodo, J.M., Lema, G., Fu, W., Nyambo, T.B., Rebbeck, T.R., et al. (2012). Evolutionary history and adaptation from high-coverage whole-genome sequences of diverse African hunter-gatherers. Cell 150, 457-469.
52. Coventry, A., Bull-Otterson, L.M., Liu, X., Clark, A.G., Maxwell, T.J., Crosby, J., Hixson, J.E., Rea, T.J., Muzny, D.M., Lewis, L.R., et al. (2010). Deep resequencing reveals excess rare recent variants consistent with explosive population growth. Nat. Commun. 1, 131.
53. Keinan, A., and Clark, A.G. (2012). Recent explosive human population growth has resulted in an excess of rare genetic variants. Science 336, 740-743.
54. Nelson, M.R.,Wegmann, D.,Ehm, M.G., Kessner, D., St Jean, P., Verzilli, C., Shen, J., Tang, Z., Bacanu, S.A., Fraser, D., et al. (2012). An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people. Science 337, 100-104.
55. United Nations, Department of Economic and Social Affairs, Population Division (2011). World Population Prospects: The 2010 Revision, Volume I: Comprehensive Tables. ST/ ESA/SERA/313. http://esa.un.org/wpp/documentation/pdf/WPP2010-Volume-I-Comprehensive-Tables.pdf.
56. Kimura, M. (1955). Stochastic processes and distribution of gene frequencies under natural selection. Cold Spring Harb. Symp. Quant. Biol. 20, 33-53.
57. Waxman, D. (2011). A unified treatment of the probability of fixation when population size and the strength of selection change over time. Genetics 188, 907-913.
58. Lohmueller, K.E. (2014). The impact of population demography and selection on the genetic architecture of complex traits. PLoS Genet. 10, e1004379.
59. Maher, M.C., Uricchio, L.H., Torgerson, D.G., and Hernandez, R.D. (2012). Population genetics of rare variants and complex diseases. Hum. Hered. 74, 118-128.
60. Gazave, E., Chang, D., Clark, A.G., and Keinan, A. (2013). Population growth inflates the per-individual number of deleterious mutations and reduces their mean effect. Genetics 195, 969-978.
61. Nei, M., Maruyama, T., and Chakraborty, R. (1975). The bottleneck effect and genetic variability in populations. Evolution 29, 1-10.
62. Atzmon, G., Hao, L., Pe'er, I., Velez, C., Pearlman, A., Palamara, P.F., Morrow, B., Friedman, E., Oddoux, C., Burns, E., and Ostrer, H. (2010). Abraham's children in the genome era: major Jewish diaspora populations comprise distinct genetic clusters with shared Middle Eastern Ancestry. Am. J. Hum. Genet. 86, 850-859.
63. Palamara, P.F., Lencz, T., Darvasi, A., and Pe'er, I. (2012). Length distributions of identity by descent reveal fine-scale demographic history. Am. J. Hum. Genet. 91, 809-822.
64. Sajantila, A., Salem, A.H., Savolainen, P., Bauer, K., Gierig, C., and Pääbo, S. (1996). Paternal and maternal DNA lineages reveal a bottleneck in the founding of the Finnish population. Proc. Natl. Acad. Sci. USA 93, 12035-12039.
65. Wang, S.R., Agarwala, V., Flannick, J., Chiang, C.W., Altshuler, D., and Hirschhorn, J.N.; GoT2D Consortium (2014). Simulation of Finnish population history, guided by empirical genetic data, to assess power of rare-variant tests in Finland. Am. J. Hum. Genet. 94, 710-720.
66. Lohmueller, K.E. (2014). The distribution of deleterious genetic variation in human populations. bioRxiv, http://dx.doi.org/10.1101/005330.