GC-Biased Evolution Near Human Accelerated Regions
Regions of the genome that have been the target of positive selection specifically along the human lineage are of special importance in human biology. We used high throughput sequencing combined with methods to enrich human genomic samples for particular targets to obtain the sequence of 22 chromosomal samples at high depth in 40 kb neighborhoods of 49 previously identified 100–400 bp elements that show evidence for human accelerated evolution. In addition to selection, the pattern of nucleotide substitutions in several of these elements suggested an historical bias favoring the conversion of weak (A or T) alleles into strong (G or C) alleles. Here we found strong evidence in the derived allele frequency spectra of many of these 40 kb regions for ongoing weak-to-strong fixation bias. Comparison of the nucleotide composition at polymorphic loci to the composition at sites of fixed substitutions additionally reveals the signature of historical weak-to-strong fixation bias in a subset of these regions. Most of the regions with evidence for historical bias do not also have signatures of ongoing bias, suggesting that the evolutionary forces generating weak-to-strong bias are not constant over time. To investigate the role of selection in shaping these regions, we analyzed the spatial pattern of polymorphism in our samples. We found no significant evidence for selective sweeps, possibly because the signal of such sweeps has decayed beyond the power of our tests to detect them. Together, these results do not rule out functional roles for the observed changes in these regions—indeed there is good evidence that the first two are functional elements in humans—but they suggest that a fixation process (such as biased gene conversion) that is biased at the nucleotide level, but is otherwise selectively neutral, could be an important evolutionary force at play in them, both historically and at present.
Vyšlo v časopise:
GC-Biased Evolution Near Human Accelerated Regions. PLoS Genet 6(5): e32767. doi:10.1371/journal.pgen.1000960
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1000960
Souhrn
Regions of the genome that have been the target of positive selection specifically along the human lineage are of special importance in human biology. We used high throughput sequencing combined with methods to enrich human genomic samples for particular targets to obtain the sequence of 22 chromosomal samples at high depth in 40 kb neighborhoods of 49 previously identified 100–400 bp elements that show evidence for human accelerated evolution. In addition to selection, the pattern of nucleotide substitutions in several of these elements suggested an historical bias favoring the conversion of weak (A or T) alleles into strong (G or C) alleles. Here we found strong evidence in the derived allele frequency spectra of many of these 40 kb regions for ongoing weak-to-strong fixation bias. Comparison of the nucleotide composition at polymorphic loci to the composition at sites of fixed substitutions additionally reveals the signature of historical weak-to-strong fixation bias in a subset of these regions. Most of the regions with evidence for historical bias do not also have signatures of ongoing bias, suggesting that the evolutionary forces generating weak-to-strong bias are not constant over time. To investigate the role of selection in shaping these regions, we analyzed the spatial pattern of polymorphism in our samples. We found no significant evidence for selective sweeps, possibly because the signal of such sweeps has decayed beyond the power of our tests to detect them. Together, these results do not rule out functional roles for the observed changes in these regions—indeed there is good evidence that the first two are functional elements in humans—but they suggest that a fixation process (such as biased gene conversion) that is biased at the nucleotide level, but is otherwise selectively neutral, could be an important evolutionary force at play in them, both historically and at present.
Zdroje
1. BejeranoG
PheasantM
MakuninI
StephenS
KentW
2004 Ultraconserved elements in the human genome. Science 304 1321 1325
2. WoolfeA
GoodsonM
GoodeDK
SnellP
McEwenGK
2005 Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol 3 e7 doi:10.1371/journal.pbio.0030007
3. PollardK
SalamaS
LambertN
LambotM
CoppensS
2006 An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443 167 172
4. PrabhakarS
NoonanJP
PääboS
RubinEM
2006 Accelerated evolution of conserved noncoding sequences in humans. Science 314 786
5. BirdCP
StrangerBE
LiuM
ThomasDJ
IngleCE
2007 Fast-evolving noncoding sequences in the human genome. Genome Biol 8 R118
6. KatzmanS
KernA
BejeranoG
FewellG
FultonL
2007 Human genome ultraconserved elements are ultraselected. Science 317 915
7. PollardK
SalamaS
KingB
KernA
DreszerT
2006 Forces shaping the fastest evolving regions in the human genome. PLoS Genet 2 e168 doi:10.1371/journal.pgen.0020168
8. PrabhakarS
ViselA
AkiyamaJ
ShoukryM
LewisK
2008 Human-specific gain of function in a developmental enhancer. Science 321 1346 1350
9. GaltierN
DuretL
2007 Adaptation or biased gene conversion? Extending the null hypothesis of molecular evolution. Trends Genet 23 273 277
10. DuretL
GaltierN
2009 Comment on “Human-specific gain of function in a developmental enhancer”. Science 323 714; author reply 714
11. StrathernJ
ShaferB
McGillC
1995 DNA synthesis errors associated with double-strand-break repair. Genetics 140 965 972
12. MaraisG
2003 Biased gene conversion: implications for genome and sex evolution. Trends Genet 19 330 338
13. MeunierJ
DuretL
2004 Recombination drives the evolution of GC-content in the human genome. Mol Biol Evol 21 984 990
14. DuretL
ArndtP
2008 The impact of recombination on nucleotide substitutions in the human genome. PLoS Genet 4 e1000071 doi:10.1371/journal.pgen.1000071
15. GaltierN
DuretL
GléminS
RanwezV
2009 GC-biased gene conversion promotes the fixation of deleterious amino acid changes in primates. Trends Genet 25 1 5
16. EnardW
PrzeworskiM
FisherSE
LaiCS
WiebeV
2002 Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418 869 872
17. RockmanMV
HahnMW
SoranzoN
ZimprichF
GoldsteinDB
2005 Ancient and recent positive selection transformed opioid cis-regulation in humans. PLoS Biol 3 e387 doi:10.1371/journal.pbio.0030387
18. HodgesE
XuanZ
BalijaV
KramerM
MollaM
2007 Genome-wide in situ exon capture for selective resequencing. Nat Genet 39 1522 1527
19. AlbertT
MollaM
MuznyD
NazarethL
WheelerD
2007 Direct selection of human genomic loci by microarray hybridization. Nat Methods 4 903 905
20. PorrecaG
ZhangK
LiJ
XieB
AustinD
2007 Multiplex amplification of large sets of human exons. Nat Methods 4 931 936
21. OkouD
SteinbergK
MiddleC
CutlerD
AlbertT
2007 Microarray-based genomic selection for high-throughput resequencing. Nat Methods 4 907 909
22. SabetiP
ReichD
HigginsJ
LevineH
RichterD
2002 Detecting recent positive selection in the human genome from haplotype structure. Nature 419 832 837
23. VoightB
KudaravalliS
WenX
PritchardJ
2006 A map of recent positive selection in the human genome. PLoS Biol 4 e72 doi:10.1371/journal.pbio.0040072
24. HaygoodR
FedrigoO
HansonB
YokoyamaKD
WrayGA
2007 Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution. Nat Genet 39 1140 1144
25. Maynard SmithJ
HaighJ
1974 The hitch-hiking effect of a favourable gene. Genet Res 23 23 35
26. KaplanN
HudsonR
LangleyC
1989 The hitchhiking effect revisited. Genetics 123 887 899
27. KimY
StephanW
2002 Detecting a local signature of genetic hitchhiking along a recombining chromosome. Genetics 160 765 777
28. NielsenR
WilliamsonS
KimY
HubiszM
ClarkA
2005 Genomic scans for selective sweeps using SNP data. Genome Res 15 1566 1575
29. WilliamsonSH
HubiszMJ
ClarkAG
PayseurBA
BustamanteCD
2007 Localizing recent adaptive evolution in the human genome. PLoS Genet 3 e90 doi:10.1371/journal.pgen.0030090
30. SabetiP
VarillyP
FryB
LohmuellerJ
HostetterE
2007 Genome-wide detection and characterization of positive selection in human populations. Nature 449 913 918
31. TangK
ThorntonK
StonekingM
2007 A New Approach for Using Genome Scans to Detect Recent Positive Selection in the Human Genome. PLoS Biol 5 e171 doi:10.1371/journal.pbio.0050171
32. Applied Biosystems SOLiD System Brochure. System Brochure. URL http://marketing.appliedbiosystems.com/images/Product_Microsites/Solid_Knowledge_MS/pdf/SOLiD_Brochure.pdf
33. AkeyJ
EberleM
RiederM
CarlsonC
ShriverM
2004 Population history and natural selection shape patterns of genetic variation in 132 genes. PLoS Biol 2 e286 doi:10.1371/journal.pbio.0020286
34. AkashiH
1999 Inferring the fitness effects of DNA mutations from polymorphism and divergence data: statistical power to detect directional selection under stationarity and free recombination. Genetics 151 221 238
35. DreszerT
WallG
HausslerD
PollardK
2007 Biased clustered substitutions in the human genome: the footprints of male-driven biased gene conversion. Genome Res 17 1420 1430
36. KongA
GudbjartssonDF
SainzJ
JonsdottirGM
GudjonssonSA
2002 A high-resolution recombination map of the human genome. Nat Genet 31 241 247
37. KentWJ
BaertschR
HinrichsA
MillerW
HausslerD
2003 Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci U S A 100 11484 11489
38. SherryS
WardM
KholodovM
BakerJ
PhanL
2001 dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29 308 311
39. TajimaF
1983 Evolutionary relationship of DNA sequences in finite populations. Genetics 105 437 460
40. WattersonGA
1975 On the number of segregating sites in genetical models without recombination. Theoretical Population Biology 7 256 276
41. PtakSE
RoederAD
StephensM
GiladY
PääboS
2004 Absence of the TAP2 human recombination hotspot in chimpanzees. PLoS Biol 2 e155 doi:10.1371/journal.pbio.0020155
42. TajimaF
1989 Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123 585 595
43. FayJC
WuCI
2000 Hitchhiking under positive Darwinian selection. Genetics 155 1405 1413
44. BlantonHL
RadfordSJ
McMahanS
KearneyHM
IbrahimJG
2005 REC, Drosophila MCM8, drives formation of meiotic crossovers. PLoS Genet 1 e40 doi:10.1371/journal.pgen.0010040
45. RadfordSJ
McMahanS
BlantonHL
SekelskyJ
2007 Heteroduplex DNA in meiotic recombination in Drosophila mei-9 mutants. Genetics 176 63 72
46. FrisseL
HudsonRR
BartoszewiczA
WallJD
DonfackJ
2001 Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels. Am J Hum Genet 69 831 843
47. Pineda-KrchM
RedfieldRJ
2005 Persistence and loss of meiotic recombination hotspots. Genetics 169 2319 2333
48. MyersS
SpencerCC
AutonA
BottoloL
FreemanC
2006 The distribution and causes of meiotic recombination in the human genome. Biochem Soc Trans 34 526 530
49. CoopG
WenX
OberC
PritchardJK
PrzeworskiM
2008 High-resolution mapping of crossovers reveals extensive variation in fine-scale recombination patterns among humans. Science 319 1395 1398
50. PetersAD
2008 A combination of cis and trans control can solve the hotspot conversion paradox. Genetics 178 1579 1593
51. BersaglieriT
SabetiPC
PattersonN
VanderploegT
SchaffnerSF
2004 Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet 74 1111 1120
52. ThompsonEE
Kuttab-BoulosH
WitonskyD
YangL
RoeBA
2004 CYP3A variation and the evolution of salt-sensitivity variants. Am J Hum Genet 75 1059 1069
53. KeightleyPD
LercherMJ
Eyre-WalkerA
2005 Evidence for widespread degradation of gene control regions in hominid genomes. PLoS Biol 3 e42 doi:10.1371/journal.pbio.0030042
54. Coriell Cell Repositories. URL http://ccr.coriell.org
55. LiH
DurbinR
2009 Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25 1754 1760
56. LiH
HandsakerB
WysokerA
FennellT
RuanJ
2009 The Sequence Alignment/Map format and SAMtools. Bioinformatics 25 2078 2079
57. PatenB
HerreroJ
BealK
FitzgeraldS
BirneyE
2008 Enredo and Pecan: genome-wide mammalian consistency-based multiple alignment with paralogs. Genome Res 18 1814 1828
58. PatenB
HerreroJ
FitzgeraldS
BealK
FlicekP
2008 Genome-wide nucleotide-level mammalian ancestor reconstruction. Genome Res 18 1829 1843
59. 1000 genomes: A deep catalog of human genetic variation. URL http://1000genomes.org
60. HudsonRR
2002 Generating samples under a Wright-Fisher neutral model of genetic variation. Bioinformatics 18 337 338
61. SiepelA
HausslerD
2004 Phylogenetic estimation of context-dependent substitution rates by maximum likelihood. Mol Biol Evol 21 468 488
62. KernAD
2009 Correcting the site frequency spectrum for divergence-based ascertainment. PLoS ONE 4 e5152 doi:10.1371/journal.pone.0005152
63. GillespieJH
1997 Junk ain't what junk does: neutral alleles in a selected context. Gene 205 291 299
64. SpencerCC
DeloukasP
HuntS
MullikinJ
MyersS
2006 The influence of recombination on human genetic diversity. PLoS Genet 2 e148 doi:10.1371/journal.pgen.0020148
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2010 Číslo 5
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
Najčítanejšie v tomto čísle
- Common Genetic Variants near the Brittle Cornea Syndrome Locus Influence the Blinding Disease Risk Factor Central Corneal Thickness
- The Relationship among Gene Expression, the Evolution of Gene Dosage, and the Rate of Protein Evolution
- SMA-10/LRIG Is a Conserved Transmembrane Protein that Enhances Bone Morphogenetic Protein Signaling
- All About Mitochondrial Eve: An Interview with Rebecca Cann