Genome-wide analysis of human hotspot intersected genes highlights the roles of meiotic recombination in evolution and disease

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• 作者：Tao Zhou (1)
  Zhibin Hu (1)
  Zuomin Zhou (1)
  Xuejiang Guo (1)
  Jiahao Sha (1)
  
• 关键词：Meiotic recombination ; Recombination hotspots ; Evolution ; Disease ; Chromosomal rearrangements ; Repeat element
• 刊名：BMC Genomics
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：14
• 期：1
• 全文大小：414KB
• 参考文献：1. Coop G, Przeworski M: An evolutionary view of human recombination. / Nat Rev Genet 2007, 8:23鈥?4. CrossRef
  2. Webster MT, Hurst LD: Direct and indirect consequences of meiotic recombination: implications for genome evolution. / Trends Genet 2012, 28:101鈥?09. CrossRef
  3. Sasaki M, Lange J, Keeney S: Genome destabilization by homologous recombination in the germ line. / Nat Rev Mol Cell Biol 2010, 11:182鈥?95.
  4. Lichten M, Goldman AS: Meiotic recombination hotspots. / Annu Rev Genet 1995, 29:423鈥?44. CrossRef
  5. Kong A, Thorleifsson G, Gudbjartsson DF, Masson G, Sigurdsson A, Jonasdottir A, Walters GB, Gylfason A, Kristinsson KT, Gudjonsson SA, / et al.: Fine-scale recombination rate differences between sexes, populations and individuals. / Nature 2010, 467:1099鈥?103. CrossRef
  6. Myers S, Bottolo L, Freeman C, McVean G, Donnelly P: A fine-scale map of recombination rates and hotspots across the human genome. / Science 2005, 310:321鈥?24. CrossRef
  7. Berg IL, Neumann R, Lam KW, Sarbajna S, Odenthal-Hesse L, May CA, Jeffreys AJ: PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans. / Nat Genet 2010, 42:859鈥?63. CrossRef
  8. Myers S, Freeman C, Auton A, Donnelly P, McVean G: A common sequence motif associated with recombination hot spots and genome instability in humans. / Nat Genet 2008, 40:1124鈥?129. CrossRef
  9. Paigen K, Petkov P: Mammalian recombination hot spots: properties, control and evolution. / Nat Rev Genet 2010, 11:221鈥?33. CrossRef
  10. Freudenberg J, Fu YH, Ptacek LJ: Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection? / Eur J Hum Genet 2007, 15:1071鈥?078. CrossRef
  11. Hynes RO, Zhao Q: The evolution of cell adhesion. / J Cell Biol 2000, 150:F89鈥?6. CrossRef
  12. Zhang L, Li WH: Mammalian housekeeping genes evolve more slowly than tissue-specific genes. / Mol Biol Evol 2004, 21:236鈥?39. CrossRef
  13. Winter EE, Goodstadt L, Ponting CP: Elevated rates of protein secretion, evolution, and disease among tissue-specific genes. / Genome Res 2004, 14:54鈥?1. CrossRef
  14. Lercher MJ, Hurst LD: Human SNP variability and mutation rate are higher in regions of high recombination. / Trends Genet 2002, 18:337鈥?40. CrossRef
  15. Hurles M: Gene duplication: the genomic trade in spare parts. / PLoS Biol 2004, 2:E206. CrossRef
  16. Ouedraogo M, Bettembourg C, Bretaudeau A, Sallou O, Diot C, Demeure O, Lecerf F: The Duplicated Genes Database: Identification and Functional Annotation of Co-Localised Duplicated Genes across Genomes. / PLoS One 2012, 7:e50653. CrossRef
  17. Zhang YE, Landback P, Vibranovski MD, Long M: Accelerated recruitment of new brain development genes into the human genome. / PLoS Biol 2011, 9:e1001179. CrossRef
  18. Long M, Betran E, Thornton K, Wang W: The origin of new genes: glimpses from the young and old. / Nat Rev Genet 2003, 4:865鈥?75. CrossRef
  19. Barreiro LB, Marioni JC, Blekhman R, Stephens M, Gilad Y: Functional comparison of innate immune signaling pathways in primates. / PLoS Genet 2010, 6:e1001249. CrossRef
  20. Gibson KR: Evolution of human intelligence: the roles of brain size and mental construction. / Brain Behav Evol 2002, 59:10鈥?0. CrossRef
  21. Dickerson JE, Robertson DL: On the origins of Mendelian disease genes in man: the impact of gene duplication. / Mol Biol Evol 2012, 29:61鈥?9. CrossRef
  22. Kong F, Zhu J, Wu J, Peng J, Wang Y, Wang Q, Fu S, Yuan LL, Li T: dbCRID: a database of chromosomal rearrangements in human diseases. / Nucleic Acids Res 2011, 39:D895鈥?00. CrossRef
  23. Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR: A census of human cancer genes. / Nat Rev Cancer 2004, 4:177鈥?83. CrossRef
  24. Pegoraro L, Palumbo A, Erikson J, Falda M, Giovanazzo B, Emanuel BS, Rovera G, Nowell PC, Croce CM: A 14;18 and an 8;14 chromosome translocation in a cell line derived from an acute B-cell leukemia. / Proc Natl Acad Sci USA 1984, 81:7166鈥?170. CrossRef
  25. Reed JC, Cuddy M, Slabiak T, Croce CM, Nowell PC: Oncogenic potential of bcl-2 demonstrated by gene transfer. / Nature 1988, 336:259鈥?61. CrossRef
  26. Date O, Katsura M, Ishida M, Yoshihara T, Kinomura A, Sueda T, Miyagawa K: Haploinsufficiency of RAD51B causes centrosome fragmentation and aneuploidy in human cells. / Cancer Res 2006, 66:6018鈥?024. CrossRef
  27. Helleday T, Lo J, van Gent DC, Engelward BP: DNA double-strand break repair: from mechanistic understanding to cancer treatment. / DNA Repair (Amst) 2007, 6:923鈥?35. CrossRef
  28. Richardson C, Moynahan ME, Jasin M: Double-strand break repair by interchromosomal recombination: suppression of chromosomal translocations. / Genes Dev 1998, 12:3831鈥?842. CrossRef
  29. Sengstag C: The role of mitotic recombination in carcinogenesis. / Crit Rev Toxicol 1994, 24:323鈥?53. CrossRef
  30. LaFave MC, Sekelsky J: Mitotic recombination: why? when? how? where? / PLoS Genet 2009, 5:e1000411. CrossRef
  31. Debacker K, Kooy RF: Fragile sites and human disease. / Hum Mol Genet 2007, 16 Spec No. 2:R150鈥?58. CrossRef
  32. Bayley JP, Weiss MM, Grimbergen A, van Brussel BT, Hes FJ, Jansen JC, Verhoef S, Devilee P, Corssmit EP, Vriends AH: Molecular characterization of novel germline deletions affecting SDHD and SDHC in pheochromocytoma and paraganglioma patients. / Endocr Relat Cancer 2009, 16:929鈥?37. CrossRef
  33. Goecks J, Nekrutenko A, Taylor J: Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences. / Genome Biol 2010, 11:R86. CrossRef
  34. Karolchik D, Hinrichs AS, Furey TS, Roskin KM, Sugnet CW, Haussler D, Kent WJ: The UCSC Table Browser data retrieval tool. / Nucleic Acids Res 2004, 32:D493鈥?96. CrossRef
  35. Pruitt KD, Tatusova T, Maglott DR: NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. / Nucleic Acids Res 2005, 33:D501鈥?04. CrossRef
  36. Chang CW, Cheng WC, Chen CR, Shu WY, Tsai ML, Huang CL, Hsu IC: Identification of human housekeeping genes and tissue-selective genes by microarray meta-analysis. / PLoS One 2011, 6:e22859. CrossRef
  37. Chen Y, Zhang Y, Yin Y, Gao G, Li S, Jiang Y, Gu X, Luo J: SPD鈥揳 web-based secreted protein database. / Nucleic Acids Res 2005, 33:D169鈥?73. CrossRef
  38. Liu X, Yu X, Zack DJ, Zhu H, Qian J: TiGER: a database for tissue-specific gene expression and regulation. / BMC Bioinformatics 2008, 9:271. CrossRef
  39. Hamosh A, Scott AF, Amberger J, Bocchini C, Valle D, McKusick VA: Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. / Nucleic Acids Res 2002, 30:52鈥?5. CrossRef
  40. Novo FJ, de Mendibil IO, Vizmanos JL: TICdb: a collection of gene-mapped translocation breakpoints in cancer. / BMC Genomics 2007, 8:33. CrossRef
  41. da Huang W, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. / Nat Protoc 2009, 4:44鈥?7. CrossRef
  42. Vilella AJ, Severin J, Ureta-Vidal A, Heng L, Durbin R, Birney E: EnsemblCompara GeneTrees: Complete, duplication-aware phylogenetic trees in vertebrates. / Genome Res 2009, 19:327鈥?35. CrossRef
  43. Wilcoxon F: Individual comparisons by ranking methods. / Biometrics 1945, 1:80鈥?3. CrossRef
  44. Jurka J: Repbase update: a database and an electronic journal of repetitive elements. / Trends Genet 2000, 16:418鈥?20. CrossRef
  
• 作者单位：Tao Zhou (1)
  Zhibin Hu (1)
  Zuomin Zhou (1)
  Xuejiang Guo (1)
  Jiahao Sha (1)
  
  1. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province, 210029, People鈥檚 Republic of China
  

文摘

Background Meiotic recombination events are not randomly located, but rather cluster at hotspot regions. Recently, the fine-scale mapping of genome-wide human recombination hotspots was performed. Here, we systematically analyzed the evolutionary and disease-associated features of hotspots that overlapped with protein-coding genes. Results In this study, we defined hotspot intersected genes as HI genes. We found that HI genes were prone to be located in the extracellular part and were functionally enriched in cell-to-cell communication. Tissue-specific genes and secreted protein encoding genes were overrepresented in HI genes, while housekeeping genes were underrepresented. Compared to slowly evolving housekeeping genes and random genes with lower recombination rates, HI genes evolved faster. The fact that brain and blood specific genes were overrepresented in HI genes indicates that they may be involved in the evolution of human intelligence and the immune system. We also found that genes related to disease were enriched in HI genes, especially genes with disease-associated chromosomal rearrangements. Hotspot sequence motifs were overrepresented in common sequences of HI genes and genes with disease-associated chromosomal rearrangements. We further listed repeat elements that were enriched both in hotspots and genes with disease-associated chromosomal rearrangements. Conclusion HI genes are evolving and may be involved in the generation of key features of human during evolution. Disease-associated genes may be by-products of meiotic recombination. In addition, hotspot sequence motifs and repeat elements showed the connection between meiotic recombination and genes with disease-associated chromosomal rearrangements at the sequence level. Our study will enable us to better understand the evolutionary and biological significance of human meiotic recombination.