Hard Selective Sweep and Ectopic Gene Conversion in a Gene Cluster Affording Environmental Adaptation
Among the rare colonizers of heavy-metal rich toxic soils, Arabidopsis halleri is a compelling model extremophile, physiologically distinct from its sister species A. lyrata, and A. thaliana. Naturally selected metal hypertolerance and extraordinarily high leaf metal accumulation in A. halleri both require Heavy Metal ATPase4 (HMA4) encoding a PIB-type ATPase that pumps Zn2+ and Cd2+ out of specific cell types. Strongly enhanced HMA4 expression results from a combination of gene copy number expansion and cis-regulatory modifications, when compared to A. thaliana. These findings were based on a single accession of A. halleri. Few studies have addressed nucleotide sequence polymorphism at loci known to govern adaptations. We thus sequenced 13 DNA segments across the HMA4 genomic region of multiple A. halleri individuals from diverse habitats. Compared to control loci flanking the three tandem HMA4 gene copies, a gradual depletion of nucleotide sequence diversity and an excess of low-frequency polymorphisms are hallmarks of positive selection in HMA4 promoter regions, culminating at HMA4-3. The accompanying hard selective sweep is segmentally eclipsed as a consequence of recurrent ectopic gene conversion among HMA4 protein-coding sequences, resulting in their concerted evolution. Thus, HMA4 coding sequences exhibit a network-like genealogy and locally enhanced nucleotide sequence diversity within each copy, accompanied by lowered sequence divergence between paralogs in any given individual. Quantitative PCR corroborated that, across A. halleri, three genomic HMA4 copies generate overall 20- to 130-fold higher transcript levels than in A. thaliana. Together, our observations constitute an unexpectedly complex profile of polymorphism resulting from natural selection for increased gene product dosage. We propose that these findings are paradigmatic of a category of multi-copy genes from a broad range of organisms. Our results emphasize that enhanced gene product dosage, in addition to neo- and sub-functionalization, can account for the genomic maintenance of gene duplicates underlying environmental adaptation.
Vyšlo v časopise:
Hard Selective Sweep and Ectopic Gene Conversion in a Gene Cluster Affording Environmental Adaptation. PLoS Genet 9(8): e32767. doi:10.1371/journal.pgen.1003707
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003707
Souhrn
Among the rare colonizers of heavy-metal rich toxic soils, Arabidopsis halleri is a compelling model extremophile, physiologically distinct from its sister species A. lyrata, and A. thaliana. Naturally selected metal hypertolerance and extraordinarily high leaf metal accumulation in A. halleri both require Heavy Metal ATPase4 (HMA4) encoding a PIB-type ATPase that pumps Zn2+ and Cd2+ out of specific cell types. Strongly enhanced HMA4 expression results from a combination of gene copy number expansion and cis-regulatory modifications, when compared to A. thaliana. These findings were based on a single accession of A. halleri. Few studies have addressed nucleotide sequence polymorphism at loci known to govern adaptations. We thus sequenced 13 DNA segments across the HMA4 genomic region of multiple A. halleri individuals from diverse habitats. Compared to control loci flanking the three tandem HMA4 gene copies, a gradual depletion of nucleotide sequence diversity and an excess of low-frequency polymorphisms are hallmarks of positive selection in HMA4 promoter regions, culminating at HMA4-3. The accompanying hard selective sweep is segmentally eclipsed as a consequence of recurrent ectopic gene conversion among HMA4 protein-coding sequences, resulting in their concerted evolution. Thus, HMA4 coding sequences exhibit a network-like genealogy and locally enhanced nucleotide sequence diversity within each copy, accompanied by lowered sequence divergence between paralogs in any given individual. Quantitative PCR corroborated that, across A. halleri, three genomic HMA4 copies generate overall 20- to 130-fold higher transcript levels than in A. thaliana. Together, our observations constitute an unexpectedly complex profile of polymorphism resulting from natural selection for increased gene product dosage. We propose that these findings are paradigmatic of a category of multi-copy genes from a broad range of organisms. Our results emphasize that enhanced gene product dosage, in addition to neo- and sub-functionalization, can account for the genomic maintenance of gene duplicates underlying environmental adaptation.
Zdroje
1. HoekstraHE, CoyneJA (2007) The locus of evolution: evo devo and the genetics of adaptation. Evolution 61: 995–1016.
2. Mitchell-OldsT, WillisJH, GoldsteinDB (2007) Which evolutionary processes influence natural genetic variation for phenotypic traits? Nat Rev Genet 8: 845–856.
3. StinchcombeJR, HoekstraHE (2008) Combining population genomics and quantitative genetics: finding the genes underlying ecologically important traits. Heredity 100: 158–170.
4. AntonovicsJ, BradshawAD, TurnerRG (1971) Heavy metal tolerance in plants. Adv Ecol Res 7: 1–85.
5. Ernst WHO (1974) Schwermetallvegetationen der Erde. Stuttgart, Germany: Gustav Fischer Verlag.
6. KrämerU (2010) Metal hyperaccumulation in plants. Annu Rev Plant Biol 61: 517–534.
7. VerbruggenN, HermansC, SchatH (2009) Molecular mechanisms of metal hyperaccumulation in plants. New Phytol 181: 759–776.
8. HanikenneM, TalkeIN, HaydonMJ, LanzC, NolteA, et al. (2008) Evolution of metal hyperaccumulation required cis-regulatory changes and triplication of HMA4. Nature 453: 391–395.
9. BoydR (2010) Elemental defenses of plants by metals. Nature Education Knowledge 1: 6.
10. ClemensS (2001) Molecular mechanisms of plant metal tolerance and homeostasis. Planta 212: 475–486.
11. BecherM, TalkeIN, KrallL, KrämerU (2004) Cross-species microarray transcript profiling reveals high constitutive expression of metal homeostasis genes in shoots of the zinc hyperaccumulator Arabidopsis halleri. Plant J 37: 251–268.
12. TalkeIN, HanikenneM, KrämerU (2006) Zinc-dependent global transcriptional control, transcriptional deregulation, and higher gene copy number for genes in metal homeostasis of the hyperaccumulator Arabidopsis halleri. Plant Physiol 142: 148–167.
13. WeberM, HaradaE, VessC, Roepenack-LahayeEV, ClemensS (2004) Comparative microarray analysis of Arabidopsis thaliana and Arabidopsis halleri roots identifies nicotianamine synthase, a ZIP transporter and other genes as potential metal hyperaccumulation factors. Plant J 37: 269–281.
14. DrägerDB, Desbrosses-FonrougeAG, KrachC, ChardonnensAN, MeyerRC, et al. (2004) Two genes encoding Arabidopsis halleri MTP1 metal transport proteins co-segregate with zinc tolerance and account for high MTP1 transcript levels. Plant J 39: 425–439.
15. DeinleinU, WeberM, SchmidtH, RenschS, TrampczynskaA, et al. (2012) Elevated nicotianamine levels in Arabidopsis halleri roots play a key role in zinc hyperaccumulation. Plant Cell 24: 708–723.
16. LinYF, LiangHM, YangSY, BochA, ClemensS, et al. (2009) Arabidopsis IRT3 is a zinc-regulated and plasma membrane localized zinc/iron transporter. New Phytol 182: 392–404.
17. CourbotM, WillemsG, MotteP, ArvidssonS, RoosensN, et al. (2007) A major QTL for Cd tolerance in Arabidopsis halleri co-localizes with HMA4, a gene encoding a heavy metal ATPase. Plant Physiol 144: 1052–1065.
18. HussainD, HaydonMJ, WangY, WongE, ShersonSM, et al. (2004) P-type ATPase heavy metal transporters with roles in essential zinc homeostasis in Arabidopsis. Plant Cell 16: 1327–1339.
19. WillemsG, DrägerDB, CourbotM, GodeC, VerbruggenN, et al. (2007) The genetic basis of zinc tolerance in the metallophyte Arabidopsis halleri ssp. halleri (Brassicaceae): An analysis of quantitative trait loci. Genetics 176: 659–674.
20. WillemsG, FrérotH, GennenJ, SalisP, Saumitou-LapradeP, et al. (2010) Quantitative trait loci analysis of mineral element concentrations in an Arabidopsis halleri×Arabidopsis lyrata petraea F2 progeny grown on cadmium-contaminated soil. New Phytol 187: 368–379.
21. FrérotH, FauconMP, WillemsG, GodeC, CourseauxA, et al. (2010) Genetic architecture of zinc hyperaccumulation in Arabidopsis halleri: the essential role of QTL×environment interactions. New Phytol 187: 355–367.
22. PapoyanA, KochianLV (2004) Identification of Thlaspi caerulescens genes that may be involved in heavy metal hyperaccumulation and tolerance. Characterization of a novel heavy metal transporting ATPase. Plant Physiol 136: 3814–3823.
23. O'LochlainnS, BowenHC, FrayRG, HammondJP, KingGJ, et al. (2011) Tandem quadruplication of HMA4 in the zinc (Zn) and cadmium (Cd) hyperaccumulator Noccaea caerulescens. PloS One 6: e17814.
24. ShahzadZ, GostiF, FrérotH, LacombeE, RoosensN, et al. (2010) The five AhMTP1 zinc transporters undergo different evolutionary fates towards adaptive evolution to zinc tolerance in Arabidopsis halleri. PLoS Genet 6: e1000911.
25. MirouzeM, SelsJ, RichardO, CzernicP, LoubetS, et al. (2006) A putative novel role for plant defensins: a defensin from the zinc hyper-accumulating plant, Arabidopsis halleri, confers zinc tolerance. Plant J 47: 329–342.
26. Ohno S (1970) Evolution by gene duplication. New York: Springer.
27. LipinskiKJ, FarslowJC, FitzpatrickKA, LynchM, KatjuV, et al. (2011) High spontaneous rate of gene duplication in Caenorhabditis elegans. Curr Biol 21: 306–310.
28. LynchM, SungW, MorrisK, CoffeyN, LandryCR, et al. (2008) A genome-wide view of the spectrum of spontaneous mutations in yeast. Proc Natl Acad Sci U S A 105: 9272–9277.
29. ChenJM, CooperDN, ChuzhanovaN, FerecC, PatrinosGP (2007) Gene conversion: mechanisms, evolution and human disease. Nat Rev Genet 8: 762–775.
30. MichaelsonJJ, ShiY, GujralM, ZhengH, MalhotraD, et al. (2012) Whole-genome sequencing in autism identifies hot spots for de novo germline mutation. Cell 151: 1431–1442.
31. LynchM, ConeryJS (2000) The evolutionary fate and consequences of duplicate genes. Science 290: 1151–1155.
32. InnanH, KondrashovF (2010) The evolution of gene duplications: classifying and distinguishing between models. Nat Rev Genet 11: 97–108.
33. MichelmoreRW, MeyersBC (1998) Clusters of resistance genes in plants evolve by divergent selection and a birth-and-death process. Genome Res 8: 1113–1130.
34. SuttonT, BaumannU, HayesJ, CollinsNC, ShiBJ, et al. (2007) Boron-toxicity tolerance in barley arising from efflux transporter amplification. Science 318: 1446–1449.
35. MaronLG, GuimaraesCT, KirstM, AlbertPS, BirchlerJA, et al. (2013) Aluminum tolerance in maize is associated with higher MATE1 gene copy number. Proc Natl Acad Sci U S A 110: 5241–5246.
36. PerryGH, DominyNJ, ClawKG, LeeAS, FieglerH, et al. (2007) Diet and the evolution of human amylase gene copy number variation. Nat Genet 39: 1256–1260.
37. KondrashovFA (2012) Gene duplication as a mechanism of genomic adaptation to a changing environment. Phil Trans R Soc B 279: 5048–5057.
38. KubotaH, TakenakaC (2003) Arabis gemmifera is a hyperaccumulator of Cd and Zn. Int J Phytoremediation 5: 197–201.
39. HuTT, PattynP, BakkerEG, CaoJ, ChengJF, et al. (2011) The Arabidopsis lyrata genome sequence and the basis of rapid genome size change. Nat Genet 43: 476–481.
40. BartonNH (2000) Genetic hitchhiking. Phil Trans R Soc B 355: 1553–1562.
41. Ramos-OnsinsSE, StrangerBE, Mitchell-OldsT, AguadeM (2004) Multilocus analysis of variation and speciation in the closely related species Arabidopsis halleri and A. lyrata. Genetics 166: 373–388.
42. HeidelAJ, Ramos-OnsinsSE, WangWK, ChiangTY, Mitchell-OldsT (2010) Population history in Arabidopsis halleri using multilocus analysis. Mol Ecol 19: 3364–3379.
43. RouxC, CastricV, PauwelsM, WrightSI, Saumitou-LapradeP, et al. (2011) Does speciation between Arabidopsis halleri and Arabidopsis lyrata coincide with major changes in a molecular target of adaptation? PloS One 6: e26872.
44. FuYX, LiWH (1993) Statistical tests of neutrality of mutations. Genetics 133: 693–709.
45. TajimaF (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123: 585–595.
46. PuruggananMD, FullerDQ (2009) The nature of selection during plant domestication. Nature 457: 843–848.
47. BenovoyD, DrouinG (2009) Ectopic gene conversions in the human genome. Genomics 93: 27–32.
48. PetesTD, HillCW (1988) Recombination Between Repeated Genes in Microorganisms. Ann Rev Genet 22: 147–168.
49. CasolaC, ConantGC, HahnMW (2012) Very low rate of gene conversion in the yeast genome. Mol Biol Evol 89: 3817–3826.
50. GaoLZ, InnanH (2004) Very low gene duplication rate in the yeast genome. Science 306: 1367–1370.
51. KroymannJ, DonnerhackeS, SchnabelrauchD, Mitchell-OldsT (2003) Evolutionary dynamics of an Arabidopsis insect resistance quantitative trait locus. Proc Natl Acad Sci U S A 100: 14587–14592.
52. BoschE, HurlesME, NavarroA, JoblingMA (2004) Dynamics of a human interparalog gene conversion hotspot. Genome Res 14: 835–844.
53. AssisR, KondrashovAS (2012) A strong deletion bias in nonallelic gene conversion. PLoS Genet 8: e1002508.
54. CasolaC, ZekonyteU, PhillipsAD, CooperDN, HahnMW (2012) Interlocus gene conversion events introduce deleterious mutations into at least 1% of human genes associated with inherited disease. Genome Res 22: 429–435.
55. InnanH (2002) A method for estimating the mutation, gene conversion and recombination parameters in small multigene families. Genetics 161: 865–872.
56. InnanH (2003) The coalescent and infinite-site model of a small multigene family. Genetics 163: 803–810.
57. ManoS, InnanH (2008) The evolutionary rate of duplicated genes under concerted evolution. Genetics 180: 493–505.
58. TeshimaKM, InnanH (2012) The coalescent with selection on copy number variants. Genetics 190: 1077–1086.
59. OhtaT (1983) On the evolution of multigene families. Theor Popul Biol 23: 216–240.
60. BaekgaardL, MikkelsenMD, SorensenDM, HegelundJN, PerssonDP, et al. (2010) A combined zinc/cadmium sensor and zinc/cadmium export regulator in a heavy metal pump. J Biol Chem 285: 31243–31252.
61. ParniskeM, Hammond-KosackKE, GolsteinC, ThomasCM, JonesDA, et al. (1997) Novel disease resistance specificities result from sequence exchange between tandemly repeated genes at the Cf-4/9 locus of tomato. Cell 91: 821–832.
62. KuangH, CaldwellKS, MeyersBC, MichelmoreRW (2008) Frequent sequence exchanges between homologs of RPP8 in Arabidopsis are not necessarily associated with genomic proximity. Plant J 54: 69–80.
63. KuangH, WooSS, MeyersBC, NevoE, MichelmoreRW (2004) Multiple genetic processes result in heterogeneous rates of evolution within the major cluster disease resistance genes in lettuce. Plant Cell 16: 2870–2894.
64. Mondragon-PalominoM, GautBS (2005) Gene conversion and the evolution of three leucine-rich repeat gene families in Arabidopsis thaliana. Mol Biol Evol 22: 2444–2456.
65. BergelsonJ, KreitmanM, StahlEA, TianD (2001) Evolutionary dynamics of plant R-genes. Science 292: 2281–2285.
66. KochMA, MatschingerM (2007) Evolution and genetic differentiation among relatives of Arabidopsis thaliana. Proc Natl Acad Sci U S A 104: 6272–6277.
67. DassanayakeM, OhDH, HaasJS, HernandezA, HongH, et al. (2011) The genome of the extremophile crucifer Thellungiella parvula. Nat Genet 43: 913–918.
68. NairS, NashD, SudimackD, JaideeA, BarendsM, et al. (2007) Recurrent gene amplification and soft selective sweeps during evolution of multidrug resistance in malaria parasites. Mol Biol Evol 24: 562–573.
69. CookDE, LeeTG, GuoX, MelitoS, WangK, et al. (2012) Copy number variation of multiple genes at Rhg1 mediates nematode resistance in soybean. Science 338: 1206–1209.
70. TurnerTL, BourneEC, Von WettbergEJ, HuTT, NuzhdinSV (2010) Population resequencing reveals local adaptation of Arabidopsis lyrata to serpentine soils. Nat Genet 42: 260–263.
71. SuginoRP, InnanH (2006) Selection for more of the same product as a force to enhance concerted evolution of duplicated genes. Trends Genet 22: 642–644.
72. BertV, MacNairMR, De LaguérieP, Saumitou-LapradeP, PetitD (2000) Zinc tolerance and accumulation in metallicolous and non metallicolous populations of Arabidopsis halleri (Brassicaceae). New Phytol 146: 225–233.
73. The Arabidopsis Genome Initiative (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408: 796–815.
74. MorelM, CrouzetJ, GravotA, AuroyP, LeonhardtN, et al. (2009) AtHMA3, a P1B-ATPase allowing Cd/Zn/Co/Pb vacuolar storage in Arabidopsis. Plant Physiol 149: 894–904.
75. BradleyRD, HillisDM (1997) Recombinant DNA sequences generated by PCR amplification. Mol Biol Evol 14: 592–593.
76. LibradoP, RozasJ (2009) DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25: 1451–1452.
77. TamuraK, PetersonD, PetersonN, StecherG, NeiM, et al. (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28: 2731–2739.
78. ClementM, PosadaD, CrandallKA (2000) TCS: a computer program to estimate gene genealogies. Mol Ecol 9: 1657–1659.
79. ExcoffierL, LischerHE (2010) Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour 10: 564–567.
80. RamakersC, RuijterJM, DeprezRH, MoormanAF (2003) Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett 339: 62–66.
81. HellemansJ, MortierG, De PaepeA, SpelemanF, VandesompeleJ (2007) qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data. Genome Biol 8: R19.
82. D'HaeneB, VandesompeleJ, HellemansJ (2010) Accurate and objective copy number profiling using real-time quantitative PCR. Methods 50: 262–270.
83. VandesompeleJ, De PreterK, PattynF, PoppeB, Van RoyN, et al. (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3: RESEARCH0034.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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