The Population Genetics of dN/dS


Evolutionary pressures on proteins are often quantified by the ratio of substitution rates at non-synonymous and synonymous sites. The dN/dS ratio was originally developed for application to distantly diverged sequences, the differences among which represent substitutions that have fixed along independent lineages. Nevertheless, the dN/dS measure is often applied to sequences sampled from a single population, the differences among which represent segregating polymorphisms. Here, we study the expected dN/dS ratio for samples drawn from a single population under selection, and we find that in this context, dN/dS is relatively insensitive to the selection coefficient. Moreover, the hallmark signature of positive selection over divergent lineages, dN/dS>1, is violated within a population. For population samples, the relationship between selection and dN/dS does not follow a monotonic function, and so it may be impossible to infer selection pressures from dN/dS. These results have significant implications for the interpretation of dN/dS measurements among population-genetic samples.


Vyšlo v časopise: The Population Genetics of dN/dS. PLoS Genet 4(12): e32767. doi:10.1371/journal.pgen.1000304
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1000304

Souhrn

Evolutionary pressures on proteins are often quantified by the ratio of substitution rates at non-synonymous and synonymous sites. The dN/dS ratio was originally developed for application to distantly diverged sequences, the differences among which represent substitutions that have fixed along independent lineages. Nevertheless, the dN/dS measure is often applied to sequences sampled from a single population, the differences among which represent segregating polymorphisms. Here, we study the expected dN/dS ratio for samples drawn from a single population under selection, and we find that in this context, dN/dS is relatively insensitive to the selection coefficient. Moreover, the hallmark signature of positive selection over divergent lineages, dN/dS>1, is violated within a population. For population samples, the relationship between selection and dN/dS does not follow a monotonic function, and so it may be impossible to infer selection pressures from dN/dS. These results have significant implications for the interpretation of dN/dS measurements among population-genetic samples.


Zdroje

1. KimuraM

1977 Preponderance of synonymous changes as evidence for the neutral theory of molecular evolution. Nature 267 275 276

2. YangZ

BielawskiJP

2000 Statistical methods for detecting molecular adaptation. Trends Ecol Evol 15 496 503

3. NielsenR

YangZ

2003 Estimating the distribution of selection coefficients from phylogenetic data with applications to mitochondrial and viral DNA. Mol Biol Evol 20 1231 1239

4. GoldmanN

YangZ

1994 A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 11 725 736

5. MuseSV

GautBS

1994 A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome. Mol Biol Evol 11 715 724

6. TamuraK

DudleyJ

NeiM

KumarS

2007 MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24 1596 1599

7. YangZ

2007 PAML4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24 1586 1591

8. PlikatU

Nieselt-StruweK

MeyerhansA

1997 Genetic drift can dominate short-term human immunideficiency virus type 1 nef quasispecies evolution in vivo. J Virol 71 4233 4240

9. CrandallKA

KelseyCR

ImamichiH

LaneHC

SalzmanNP

1999 Parallel evolution of drug resistance in HIV: failure of nonsynonymous/synonymous rate ratio to detect selection. Mol Biol Evol 16 372 382

10. FrostSDW

GünthardHF

WongJK

HavlirD

RichmanDD

2001 Evidence for positive selection driving the evolution of HIV-1 env under potent antiviral therapy. Virology 284 250 258

11. FleischmannRD

AllandD

EisenJA

CarpenterL

WhiteO

2002 Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains. J Bacteriol 184 5479 5490

12. FeilEJ

CooperJE

GrundmannH

RobinsonDA

EnrightMC

2003 How clonal is Staphylococcus aureus? J Bacteriol 185 3307 3316

13. HolmesEC

2003 Patterns of intra- and interhost nonsynonymous variation reveal strong purifying selection in dengue virus. J Virol 77 11296 11298

14. JonesN

BohnsackJF

TakahashiS

OliverKA

ChanMS

2003 Multilocus sequence typing system for group B streptococcus. J Clin Microbiol 41 2530 2536

15. MeatsE

FeilEJ

StringerS

CodyAJ

GoldsteinR

2003 Characterization of encapsulated and noncapsulated Haemophilus inuenzae and determination of phylogenetic relationships by multilocus typing. J Clin Microbiol 41 1623 1636

16. HoldenMTG

FeilEJ

LindsayJA

PeacockSJ

DayNPJ

2004 Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance. Proc Natl Acad Sci USA 101 9786 9791

17. RoumagnacP

WeillFX

DolecekC

BakerS

BrisseS

2006 Evolutionary history of Salmonella Typhi. Science 314 1301 1304

18. HoltKE

ParkhillJ

MazzoniCJ

RoumagnacP

WeillFX

2008 High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi. Nat Genet 40 987 993

19. KingmanJFC

1982 On the genealogy of large populations. J Appl Prob 19 27 43

20. TajimaF

1989 Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123 585 595

21. FuYX

LiWH

1993 Statistical tests of neutrality of mutations. Genetics 133 693 709

22. FayJC

WuCI

2000 Hitchhiking under posiitve Darwinian selection. Genetics 155 1405 1413

23. SawyerSA

HartlDL

1992 Population genetics of polymorphism and divergence. Genetics 132 1161 1176

24. HartlDL

MoriyamaEN

SawyerSA

1994 Selection intensity for codon bias. Genetics 138 227 234

25. EwensWJ

2004 Mathematical population genetics New York Springer Science+Business Media, Inc

26. WrightS

1931 Evolution in Mendelian populations. Genetics 16 97 159

27. YangZ

1996 Maximum-likelihood models for combined analyses of multiple sequence data. J Mol Evol 42 587 596

28. NielsenR

YangZ

1998 Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics 148 929 936

29. YangZ

NielsenR

2000 Estimating synonymous and nonsynonymous substitution rates under realistic evolutionary models. Mol Biol Evol 17 32 43

30. YangZ

NielsenR

GoldmanN

PedersenAMK

2000 Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics 155 431 449

31. YangZ

NielsenR

2002 Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. Mol Biol Evol 19 908 917

32. MayroseI

Doron-FaigenboimA

BacharachE

PupkoT

2007 Towards realistic codon models: among site variability and dependency of synonymous and non-synononymous rates. Bioinformatics 23 i319 i327

33. ForsbergR

ChristiansenFB

2003 A codon-based model of host-specific selection in parasites, with an application to the influenza A virus. Mol Biol Evol 20 1252 1259

34. GuindonS

RodrigoAG

DyerKA

HuelsenbeckJP

2004 Modeling the site-specific variation of selection patterns along lineages. Proc Natl Acad Sci USA 101 12957 12962

35. YangZ

NielsenR

2008 Mutation-selection models of codon substitution and their use to estimate selective strengths on codon usage. Mol Biol Evol 25 568 579

36. HaighJ

1978 The accumulation of deleterious genes in a population—Muller's ratchet. Theor Pop Biol 14 251 267

37. GordoI

CharlesworthB

2000 The degradation of asexual haploid populations and the speed of Muller's ratchet. Genetics 154 1379 1387

38. GerrishPJ

LenskiRE

1998 The fate of competing beneficial mutations in an asexual population. Genetica 102/103 127 144

39. ParkSC

KrugJ

2007 Clonal interference in large populations. Proc Natl Acad Sci USA 104 18135 18140

40. DesaiMM

FisherDS

2007 Beneficial mutation-selection balance and the effect of linkage on positive selection. Genetics 176 1759 1798

41. RouzineIM

BrunetE

WilkeCO

2008 The traveling-wave approach to asexual evolution: Muller's ratchet and speed of adaptation. Theor Pop Biol 73 24 46

42. WrightS

1945 The differential equation of the distribution of gene frequencies. Proc Natl Acad Sci USA 31 382 389

43. MustonenV

LässigM

2007 Adaptations to fluctuating selection in Drosophila. PNAS 104 2277 2282

44. RochaEPC

SmithJM

HurstLD

HoldenMTG

CooperJE

2006 Comparison of dN/dS are time dependent for closely related bacterial genomes. J Theor Biol 239 226 235

45. McDonaldJH

KreitmanM

1991 Adaptive protein evolution at the Adh locus in Drosophila. Nature 351 652 654

46. LiuJ

ZhangY

LeiX

ZhangZ

2008 Natural selection of protein structural and functional properties: a single nucleotide polymorphism perspective. Genome Biology 9 R69

47. CharlesworthJ

Eyre-WalkerA

2008 The McDonald-Kreitman test and slightly deleterious mutations. Mol Biol Evol 25 1007 1015

48. SharpPM

BailesE

ChaudhuriRR

RodenburgCM

SantiagoMO

2001 The origins of acquired immune deficiency syndrom viruses: where and when? Phil Trans R Soc Lond B 356 867 876

49. HasegawaM

CaoY

YangZ

1998 Preponderance of slightly deleterious polymorphisms in mitochondrial DNA: nonsynonymous/synonymous rate ratio is much higher within species than between species. Mol Biol Evol 15 1499 1505

50. ZhangL

LiWH

2005 Human SNPs reveal no evidence of frequent positive selection. Mol Biol Evol 22 2504 2507

51. TakahataN

SattaY

KleinJ

1995 Divergence time and population size in lineage leading to modern humans. Theor Pop Biol 48 198 221

52. AdachiJ

HasegawaM

1996 Tempo and mode of synonymous substitutions in mitochondrial DNA in primates. Mol Biol Evol 13 200 208

53. JordanIK

RogozinIB

WolfYI

KooninEV

2002 Microevolutionary genomics in bacteria. Theor Pop Biol 61 435 447

54. OhtaT

1992 The nearly neutral theory of molecular evolution. Annu Rev Ecol Syst 23 263 286

55. BallardJWO

KreitmanM

1995 Is mitochondrial DNA a strictly neutral marker? Trends Ecol Evol 10 485 488

56. WolfYI

ViboudC

HolmesEC

KooninEV

LipmanDJ

2006 Long intervals of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza A virus. Biol Direct 1 34 53

57. SharpPM

1997 In search for molecular darwinism. Nature 385 111 112

58. HolmesEC

de A ZanottoPM

1997 Genetic drift of human immunodeficiency virus type 1. J Virol 72 886 887

59. de A ZanottoPM

KallasEG

de SouzaRF

HolmesEC

1999 Genealogical evidence for positive selection in the nef gene of HIV-1. Genetics 153 1077 1089

60. ViboudC

BjørnstadON

SmithDL

SimonsenL

MillerMA

2006 Synchrony, waves, and spatial hierarchies in the spread of influenza. Science 447 451

Štítky
Genetika Reprodukčná medicína
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa