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Genetic Recombination Is Targeted towards Gene Promoter Regions in Dogs


The identification of the H3K4 trimethylase, PRDM9, as the gene responsible for recombination hotspot localization has provided considerable insight into the mechanisms by which recombination is initiated in mammals. However, uniquely amongst mammals, canids appear to lack a functional version of PRDM9 and may therefore provide a model for understanding recombination that occurs in the absence of PRDM9, and thus how PRDM9 functions to shape the recombination landscape. We have constructed a fine-scale genetic map from patterns of linkage disequilibrium assessed using high-throughput sequence data from 51 free-ranging dogs, Canis lupus familiaris. While broad-scale properties of recombination appear similar to other mammalian species, our fine-scale estimates indicate that canine highly elevated recombination rates are observed in the vicinity of CpG rich regions including gene promoter regions, but show little association with H3K4 trimethylation marks identified in spermatocytes. By comparison to genomic data from the Andean fox, Lycalopex culpaeus, we show that biased gene conversion is a plausible mechanism by which the high CpG content of the dog genome could have occurred.


Vyšlo v časopise: Genetic Recombination Is Targeted towards Gene Promoter Regions in Dogs. PLoS Genet 9(12): e32767. doi:10.1371/journal.pgen.1003984
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003984

Souhrn

The identification of the H3K4 trimethylase, PRDM9, as the gene responsible for recombination hotspot localization has provided considerable insight into the mechanisms by which recombination is initiated in mammals. However, uniquely amongst mammals, canids appear to lack a functional version of PRDM9 and may therefore provide a model for understanding recombination that occurs in the absence of PRDM9, and thus how PRDM9 functions to shape the recombination landscape. We have constructed a fine-scale genetic map from patterns of linkage disequilibrium assessed using high-throughput sequence data from 51 free-ranging dogs, Canis lupus familiaris. While broad-scale properties of recombination appear similar to other mammalian species, our fine-scale estimates indicate that canine highly elevated recombination rates are observed in the vicinity of CpG rich regions including gene promoter regions, but show little association with H3K4 trimethylation marks identified in spermatocytes. By comparison to genomic data from the Andean fox, Lycalopex culpaeus, we show that biased gene conversion is a plausible mechanism by which the high CpG content of the dog genome could have occurred.


Zdroje

1. MyersS, BowdenR, TumianA, BontropRE, FreemanC, et al. (2010) Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination. Science 327: 876–879.

2. BaudatF, BuardJ, GreyC, Fledel-AlonA, OberC, et al. (2010) PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327: 836–840.

3. ParvanovED, PetkovPM, PaigenK (2010) Prdm9 controls activation of mammalian recombination hotspots. Science 327: 835.

4. SmagulovaF, GregorettiIV, BrickK, KhilP, Camerini-OteroRD, et al. (2011) Genome-wide analysis reveals novel molecular features of mouse recombination hotspots. Nature 472: 375–378.

5. BuardJ, BarthesP, GreyC, de MassyB (2009) Distinct histone modifications define initiation and repair of meiotic recombination in the mouse. EMBO J 28: 2616–2624.

6. BrickK, SmagulovaF, KhilP, Camerini-OteroRD, PetukhovaGV (2012) Genetic recombination is directed away from functional genomic elements in mice. Nature 485: 642–645.

7. BergIL, NeumannR, LamKW, SarbajnaS, Odenthal-HesseL, et al. (2010) PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans. Nat Genet 42: 859–863.

8. BergIL, NeumannR, SarbajnaS, Odenthal-HesseL, ButlerNJ, et al. (2011) Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations. Proc Natl Acad Sci U S A 108: 12378–12383.

9. HinchAG, TandonA, PattersonN, SongY, RohlandN, et al. (2011) The landscape of recombination in African Americans. Nature 476: 170–175.

10. AutonA, Fledel-AlonA, PfeiferS, VennO, SegurelL, et al. (2012) A fine-scale chimpanzee genetic map from population sequencing. Science 336: 193–198.

11. OliverPL, GoodstadtL, BayesJJ, BirtleZ, RoachKC, et al. (2009) Accelerated evolution of the Prdm9 speciation gene across diverse metazoan taxa. PLoS Genet 5: e1000753.

12. MiholaO, TrachtulecZ, VlcekC, SchimentiJC, ForejtJ (2009) A mouse speciation gene encodes a meiotic histone H3 methyltransferase. Science 323: 373–375.

13. AxelssonE, WebsterMT, RatnakumarA, PontingCP, Lindblad-TohK (2012) Death of PRDM9 coincides with stabilization of the recombination landscape in the dog genome. Genome Res 22: 51–63.

14. MyersS, BottoloL, FreemanC, McVeanG, DonnellyP (2005) A fine-scale map of recombination rates and hotspots across the human genome. Science 310: 321–324.

15. McVeanGA, MyersSR, HuntS, DeloukasP, BentleyDR, et al. (2004) The fine-scale structure of recombination rate variation in the human genome. Science 304: 581–584.

16. JeffreysAJ, NeumannR, PanayiM, MyersS, DonnellyP (2005) Human recombination hot spots hidden in regions of strong marker association. Nat Genet 37: 601–606.

17. BoykoAR, BoykoRH, BoykoCM, ParkerHG, CastelhanoM, et al. (2009) Complex population structure in African village dogs and its implications for inferring dog domestication history. Proc Natl Acad Sci U S A 106: 13903–13908.

18. VaysseA, RatnakumarA, DerrienT, AxelssonE, Rosengren PielbergG, et al. (2011) Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping. PLoS Genet 7: e1002316.

19. WongAK, RuheAL, DumontBL, RobertsonKR, GuerreroG, et al. (2010) A comprehensive linkage map of the dog genome. Genetics 184: 595–605.

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

21. MyersS, FreemanC, AutonA, DonnellyP, McVeanG (2008) A common sequence motif associated with recombination hot spots and genome instability in humans. Nat Genet 40: 1124–1129.

22. The International HapMap Consortium (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449: 851–861.

23. Lindblad-TohK, WadeCM, MikkelsenTS, KarlssonEK, JaffeDB, et al. (2005) Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438: 803–819.

24. DuretL, GaltierN (2009) Biased gene conversion and the evolution of mammalian genomic landscapes. Annu Rev Genomics Hum Genet 10: 285–311.

25. HanL, ZhaoZ (2009) Contrast features of CpG islands in the promoter and other regions in the dog genome. Genomics 94: 117–124.

26. HanL, SuB, LiWH, ZhaoZ (2008) CpG island density and its correlations with genomic features in mammalian genomes. Genome Biol 9: R79.

27. PanJ, SasakiM, KniewelR, MurakamiH, BlitzblauHG, et al. (2011) A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation. Cell 144: 719–731.

28. TischfieldSE, KeeneyS (2012) Scale matters: the spatial correlation of yeast meiotic DNA breaks with histone H3 trimethylation is driven largely by independent colocalization at promoters. Cell Cycle 11: 1496–1503.

29. HayashiK, YoshidaK, MatsuiY (2005) A histone H3 methyltransferase controls epigenetic events required for meiotic prophase. Nature 438: 374–378.

30. Gray AP (1954) Mammalian hybrids; a check-list with bibliography. Farnham Royal, Bucks,: Commonwealth Agricultural Bureaux. x, 144 p. p.

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

32. McKennaA, HannaM, BanksE, SivachenkoA, CibulskisK, et al. (2010) The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20: 1297–1303.

33. BrowningBL, YuZ (2009) Simultaneous genotype calling and haplotype phasing improves genotype accuracy and reduces false-positive associations for genome-wide association studies. Am J Hum Genet 85: 847–861.

34. ZhangY, LiuT, MeyerCA, EeckhouteJ, JohnsonDS, et al. (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biol 9: R137.

35. KirknessEF, BafnaV, HalpernAL, LevyS, RemingtonK, et al. (2003) The dog genome: survey sequencing and comparative analysis. Science 301: 1898–1903.

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Genetika Reprodukčná medicína

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