Contributions of Protein-Coding and Regulatory Change to Adaptive Molecular Evolution in Murid Rodents

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The contribution of regulatory versus protein change to adaptive evolution has long been controversial. In principle, the rate and strength of adaptation within functional genetic elements can be quantified on the basis of an excess of nucleotide substitutions between species compared to the neutral expectation or from effects of recent substitutions on nucleotide diversity at linked sites. Here, we infer the nature of selective forces acting in proteins, their UTRs and conserved noncoding elements (CNEs) using genome-wide patterns of diversity in wild house mice and divergence to related species. By applying an extension of the McDonald-Kreitman test, we infer that adaptive substitutions are widespread in protein-coding genes, UTRs and CNEs, and we estimate that there are at least four times as many adaptive substitutions in CNEs and UTRs as in proteins. We observe pronounced reductions in mean diversity around nonsynonymous sites (whether or not they have experienced a recent substitution). This can be explained by selection on multiple, linked CNEs and exons. We also observe substantial dips in mean diversity (after controlling for divergence) around protein-coding exons and CNEs, which can also be explained by the combined effects of many linked exons and CNEs. A model of background selection (BGS) can adequately explain the reduction in mean diversity observed around CNEs. However, BGS fails to explain the wide reductions in mean diversity surrounding exons (encompassing ∼100 Kb, on average), implying that there is a substantial role for adaptation within exons or closely linked sites. The wide dips in diversity around exons, which are hard to explain by BGS, suggest that the fitness effects of adaptive amino acid substitutions could be substantially larger than substitutions in CNEs. We conclude that although there appear to be many more adaptive noncoding changes, substitutions in proteins may dominate phenotypic evolution.

Vyšlo v časopise: Contributions of Protein-Coding and Regulatory Change to Adaptive Molecular Evolution in Murid Rodents. PLoS Genet 9(12): e32767. doi:10.1371/journal.pgen.1003995
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003995

Souhrn

Zdroje

1. International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431 : 931–945.

2. HalliganDL, OliverF, Eyre-WalkerA, HarrB, KeightleyPD (2010) Evidence for pervasive adaptive protein evolution in wild mice. PLoS Genet 6: e1000825.

3. Phifer-RixeyM, BonhommeF, BoursotP, ChurchillGA, PialekJ, et al. (2012) Adaptative evolution and effective population size in wild house mice. Mol Biol Evol 29 : 2949–2955.

4. CarnerioM, AlbertFW, Melo-FerreiraJ, GaltierN, GayralP, et al. (2012) Evidence for widespread positive and purifying selection across the European rabbit (Oryctolagus cuniculus) genome. Mol Biol Evol 29 : 1837–1849.

5. Lindblad-TohK, GarberM, ZukO, LinMF, ParkerBJ, et al. (2011) A High-resolution map of human evolutionary constraint using 29 mammals. Nature 478 : 476–482.

6. The ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489 : 57–74.

7. DoolittleWF (2013) Is junk DNA bunk? A critique of ENCODE. PNAS 110 : 5294–5300.

8. GraurD, ZhengY, PriceN, AzevedoRBR, ZufallRA, ElhaikE (2013) On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE. Genome Biol Evol 5 : 578–590.

9. KingM-C, WilsonAC (1975) Evolution at two levels in humans and chimpanzees. Science 188 : 107–116.

10. CarrollSB (2005) Evolution at two levels: on genes and form. PLoS Biol 3 : 1159.

11. WrayGA (2007) The evolutionary significance of cis-regulatory mutations. Nat Rev Genet 8 : 206–216.

12. JonesFC, GrabherrMG, ChanYF, RussellP, MauceliE, et al. (2012) The genomic basis of adaptive evolution in threespine sticklebacks. Nature 484 : 55–61.

13. HoekstraHE, CoyneJA (2007) The locus of evolution: evo devo and the genetics of adaptation. Evolution 61 : 995–1016.

14. AndolfattoP (2005) Adaptive evolution of non-coding DNA in Drosophila. Nature 437 : 1149–1152.

15. TorgersonDG, BoykoAR, HernandezRD, IndapA, HuX, et al. (2009) Evolutionary processes acting on candidate cis-regulatory regions in humans inferred from patterns of polymorphism and divergence. PLoS Genet 5: e1000592.

16. KousathanasA, OliverF, HalliganDL, KeightleyPD (2011) Positive and negative selection on noncoding DNA close to protein-coding genes in wild house mice. Mol Biol Evol 28 : 1183–1191.

17. HalliganDL, OliverF, GuthrieJ, StemshornKC, HarrB, et al. (2011) Positive and negative selection in murine ultra-conserved noncoding elements. Mol Biol Evol 28 : 2651–2660.

18. BainesJF, HarrB (2007) Reduced X-linked diversity in derived populations of house mice. Genetics 175 : 1911–1921.

19. LoweCB, KellisM, SiepelA, RaneyBJ, ClampM, et al. (2011) Three periods of regulatory innovation during vertebrate evolution. Science 333 : 1019–1024.

20. ShenY, YueF, McClearyDF, YeZ, EdsallL, et al. (2012) A map of the cis-regulatory sequences in the mouse genome. Nature 488 : 116–120.

21. SiepelA, BejeranoG, PedersenJS, HinrichsAS, HouM, et al. (2005) Evolutionarily conserved elements in vertebrate, insect,worm, and yeast genomes. Genome Res 15 : 1034–1050.

22. AndolfattoP (2008) Controlling type-I error of the McDonald-Kreitman test in genome wide scans for selection on noncoding DNA. Genetics 180 : 1767–71.

23. ChamaryJV, ParmleyJL, HurstLD (2006) Hearing silence: non-neutral evolution at synonymous sites in mammals. Nature Reviews Genetics 7 : 98–108.

24. DohertyA, McInerneyJO (2013) Translational selection frequently overcomes genetic drift in shaping synonymous codon usage patterns in vertebrates. Mol Biol Evol 30 : 2263–2267 doi:10.1093/molbev/mst128

25. EőryL, HalliganDL, KeightleyPD (2010) Distribution of selectively constrained sites and the deleterious mutation rate in the hominid and murid genomes. Mol Biol Evol 27 : 177–192.

26. LunterG, PontingCP, HeinJ (2006) Genome-wide identification of human functional DNA using a neutral indel model. PLoS Comput Biol 2: e5.

27. SalcedoT, GeraldesA, NachmanMW (2007) Nucleotide variation in wild and inbred mice. Genetics 177 : 2277–2291.

28. KeightleyPD, Eyre-WalkerA (2007) Joint inference of the distribution of fitness effects of deleterious mutations and population demography based on nucleotide polymorphism frequencies. Genetics 177 : 2251–2261.

29. Eyre-WalkerA, WoolfitM, PhelpsT (2006) The distribution of fitness of new deleterious amino acid mutations in humans. Genetics 173 : 891–900.

30. BoykoAR, WilliamsonSH, IndapAR, DegenhardtJD, HernandezRD, et al. (2008) Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genetics 4: e1000083.

31. KousathanasA, KeightleyPD (2013) Comparing models for inferring the distribution of fitness effects of new mutations. Genetics 193 : 1197–1208.

32. Eyre-WalkerA, KeightleyPD (2009) Estimating the rate of adaptive molecular evolution in the presence of slightly deleterious mutations and population size change. Mol Biol Evol 26 : 2097–2108.

33. McDonaldJH, KreitmanM (1991) Adaptive protein evolution at the Adh locus in Drosophila. Nature 351 : 652–654.

34. MesserPW, PetrovDA (2013) Frequent adaptation and the McDonald-Kreitman test. Proc Natl Acad Sci., USA 110 : 8615–8620.

35. SattathS, ElyashivE, KolodnyO, RinottY, SellaG (2011) Pervasive adaptive protein evolution apparent in diversity patterns around amino acid substitutions in Drosophila simulans. PLoS Genetics 7: e1001302.

36. HernandezRD, KelleyJL, ElyashivE, MeltonSC, AutonA, et al. (2011) Classic selective sweeps were rare in recent human evolution. Science 331 : 920–924.

37. WieheTHE, StephanW (1993) Analysis of a genetic hitchhiking model and its application to DNA polymorphism data from Drosophila melanogaster. Mol Biol Evol 10 : 842–854.

38. CaiJJ, MacphersonMJ, SellaG, PetrovDA (2009) Pervasive hitchhiking at coding and regulatory sites in humans. PLoS Genet 5: e1000336.

39. McVickerG, GordonD, DavisC, GreenP (2009) Widespread genomic signatures of natural selection in hominid evolution. PLoS Genet 5: e1000471.

40. NordborgM, CharlesworthB, CharlesworthD (1996) The effect of recombination on background selection. Genet Res 67 : 159–174.

41. CharlesworthB, MorganMT, CharlesworthD (1993) The effect of deleterious mutations on neutral molecular variation. Genetics 134 : 1289–1303.

42. Jensen-SeamanMI, FureyTS, PayseurBA, LuY, RoskinKM, et al. (2004) Comparative recombination rates in the rat, mouse, and human genomes. Genome Res 14 : 528–538.

43. KeightleyPD, Eyre-WalkerA (2010) What can we learn about the distribution of fitness effects of new mutations from DNA sequence data? Phil Trans R Soc B 365 : 1187–1193.

44. WardLD, KellisM (2012) Evidence of abundant purifying selection in humans for recently-acquired regulatory functions. Science 337 : 1675–1678.

45. PrzeworskiM, CoopG, WallJD (2005) The signature of selection on standing genetic variation. Evolution 59 : 2312–2323.

46. PeterBM, Huerta-SanchezE, NielsenR (2012) Distinguishing between selective sweeps from standing variation and from a de novo mutation. PLoS Genet 8: e1003011.

47. PritchardJK, StephensM, DonnellyPJ (2000) Inference of population structure using multilocus genotype data. Genetics 155 : 945–959.

48. LiH, HandsakerB, WysokerA, FennellT, RuanJ, et al. (2009) The Sequence alignment/map (SAM) format and SAMtools. Bioinformatics 25 : 2078–2079.

49. KeightleyPD, HalliganDL (2011) Inference of site frequency spectra from high-throughput sequence data: quantification of selection on nonsynonymous and synonymous sites in humans. Genetics 188 : 931–940.

50. LiH, DurbinR (2009) Fast and accurate short read alignment with Burrows-Wheeler Transform. Bioinformatics 25 : 1754–1760.

51. KimuraM (1980) A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. Journal of Molecular Evolution 16 : 111–120.

52. KeightleyPD, Eyre-WalkerA (2012) Estimating the rate of adaptive molecular evolution when the evolutionary divergence between species is small. Journal of Molecular Evolution 74 : 61–68.

53. CoxA, Ackert-BicknellCL, DumontBL, DingY, BellJT, et al. (2009) A new standard genetic map for the laboratory mouse. Genetics 182 : 1335–1344.