Science China Life Sciences

, Volume 62, Issue 4, pp 467–488 | Cite as

Characterization and evolutionary dynamics of complex regions in eukaryotic genomes

  • José RanzEmail author
  • Bryan Clifton


Complex regions in eukaryotic genomes are typically characterized by duplications of chromosomal stretches that often include one or more genes repeated in a tandem array or in relatively close proximity. Nevertheless, the repetitive nature of these regions, together with the often high sequence identity among repeats, have made complex regions particularly recalcitrant to proper molecular characterization, often being misassembled or completely absent in genome assemblies. This limitation has prevented accurate functional and evolutionary analyses of these regions. This is becoming increasingly relevant as evidence continues to support a central role for complex genomic regions in explaining human disease, developmental innovations, and ecological adaptations across phyla. With the advent of long-read sequencing technologies and suitable assemblers, the development of algorithms that can accommodate sample heterozygosity, and the adoption of a pangenomic-like view of these regions, accurate reconstructions of complex regions are now within reach. These reconstructions will finally allow for accurate functional and evolutionary studies of complex genomic regions, underlying the generation of genotype-phenotype maps of unprecedented resolution.


complex genomic regions sequencing technologies genome assembly structural variation tandem gene duplicates evolutionary novelty 



This work was supported by a National Science Foundation Grant (MCB-1157876) to J.M.R.


  1. Abel, H.J., and Duncavage, E.J. (2013). Detection of structural DNA variation from next generation sequencing data: a review of informatic approaches. Cancer Genets 206, 432–440.Google Scholar
  2. Absalan, F., and Ronaghi, M. (2007). Molecular inversion probe assay. Methods Mol Biol 396, 315–330.Google Scholar
  3. Abu Bakar, S., Hollox, E.J., and Armour, J.A.L. (2009). Allelic recombination between distinct genomic locations generates copy number diversity in human β–defensins. Proc Natl Acad Sci USA 106, 853–858.Google Scholar
  4. Abyzov, A., Urban, A.E., Snyder, M., and Gerstein, M. (2011). CNVnator: An approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing. Genome Res 21, 974–984.Google Scholar
  5. Adams, M.D., Celniker, S.E., Holt, R.A., Evans, C.A, Gocayne, J.D., Amanatides, P.G., Scherer, S.E., Li, P.W., Hoskins, R.A., Galle, R.F., et al. (2000). The genome sequence of Drosophila melanogaster. Science 287, 2185–2195.Google Scholar
  6. Alberts, B. (2008). Molecular Biology of the Cell, 5th edn (New York: Garland Science).Google Scholar
  7. Alkan, C., Coe, B.P., and Eichler, E.E. (2011a). Genome structural variation discovery and genotyping. Nat Rev Genet 12, 363–376.Google Scholar
  8. Alkan, C., Sajjadian, S., and Eichler, E.E. (2011b). Limitations of nextgeneration genome sequence assembly. Nat Methods 8, 61–65.Google Scholar
  9. Ananiev, E.V., Chamberlin, M.A., Klaiber, J., and Svitashev, S. (2005). Microsatellite megatracts in the maize (Zea mays L.) genome. Genome 48, 1061–1069.Google Scholar
  10. Andersson, D.I., Jerlström–Hultqvist, J., and Näsvall, J. (2015). Evolution of new functions de novo and from preexisting genes. Cold Spring Harb Perspect Biol 7, a017996.Google Scholar
  11. Anhuf, D., Eggermann, T., Rudnik–Schöneborn, S., and Zerres, K. (2003). Determination of SMN1 and SMN2 copy number using TaqMan™ technology. Hum Mutat 22, 74–78.Google Scholar
  12. Arabidopsis Genome Initiative. (2000). Analysis of the genome sequence of the flowering plant Arabidopsis thaliana, Nature 408, 796–815.Google Scholar
  13. Arguello, J.R., Chen, Y., Yang, S., Wang, W., and Long, M. (2006). Origination of an X–linked testes chimeric gene by illegitimate recombination in Drosophila. PLoS Genet 2, e77.Google Scholar
  14. Arguello, J.R., and Connallon, T. (2011). Gene duplication and ectopic gene conversion in Drosophila. Genes 2, 131–151.Google Scholar
  15. Assogba, B.S., Milesi, P., Djogbénou, L.S., Berthomieu, A., Makoundou, P., Baba–Moussa, L.S., Fiston–Lavier, A.S., Belkhir, K., Labbé, P., and Weill, M. (2016). The ace–1 locus is amplified in all resistant anopheles gambiae mosquitoes: fitness consequences of homogeneous and heterogeneous duplications. PLoS Biol 14, e2000618.Google Scholar
  16. Baltimore, D. (1981). Gene conversion: some implications for immunoglobulin genes. Cell 24, 592–594.Google Scholar
  17. Bankevich, A., Nurk, S., Antipov, D., Gurevich, A.A., Dvorkin, M., Kulikov, A.S., Lesin, V.M., Nikolenko, S.I., Pham, S., Prjibelski, A.D., et al. (2012). SPAdes: a new genome assembly algorithm and its applications to single–cell sequencing. J Comput Biol 19, 455–477.Google Scholar
  18. Bass, C., and Field, L.M. (2011). Gene amplification and insecticide resistance. Pest Manag Sci 67, 886–890.Google Scholar
  19. Bellos, E., Johnson, M.R., and Coin, L.J.M. (2012). cnvHiTSeq: integrative models for high–resolution copy number variation detection and genotyping using population sequencing data. Genome Biol 13, R120.Google Scholar
  20. Bennett–Baker, P.E., and Mueller, J.L. (2017). CRISPR–mediated isolation of specific megabase segments of genomic DNA. Nucleic Acids Res 45, e165.Google Scholar
  21. Bentley, D.R., Balasubramanian, S., Swerdlow, H.P., Smith, G.P., Milton, J., Brown, C.G., Hall, K.P., Evers, D.J., Barnes, C.L., Bignell, H.R., et al. (2008). Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456, 53–59.Google Scholar
  22. Bergthorsson, U., Andersson, D.I., and Roth, J.R. (2007). Ohno’s dilemma: Evolution of new genes under continuous selection. Proc Natl Acad Sci USA 104, 17004–17009.Google Scholar
  23. Berlin, K., Koren, S., Chin, C.S., Drake, J.P., Landolin, J.M., and Phillippy, A.M. (2015). Assembling large genomes with single–molecule sequencing and locality–sensitive hashing. Nat Biotechnol 33, 623–630.Google Scholar
  24. Béziat, V., Traherne, J.A., Liu, L.L., Jayaraman, J., Enqvist, M., Larsson, S., Trowsdale, J., and Malmberg, K.J. (2013). Influence of KIR gene copy number on natural killer cell education. Blood 121, 4703–4707.Google Scholar
  25. Bleidorn, C. (2016). Third generation sequencing: technology and its potential impact on evolutionary biodiversity research. Systatics Biodiversity 14, 1–8.Google Scholar
  26. Bresler, M., Sheehan, S., Chan, A.H., and Song, Y.S. (2012). Telescoper: de novo assembly of highly repetitive regions. Bioinformatics 28, i311–i317.Google Scholar
  27. Buermans, H.P.J., Vossen, R.H.A.M., Anvar, S.Y., Allard, W.G., Guchelaar, H.J., White, S.J., den Dunnen, J.T., Swen, J.J., and van der Straaten, T. (2017). Flexible and scalable full–length CYP2D6 long amplicon PacBio sequencing. Human Mutat 38, 310–316.Google Scholar
  28. Campbell, P.J., Stephens, P.J., Pleasance, E.D., O’Meara, S., Li, H., Santarius, T., Stebbings, L.A., Leroy, C., Edkins, S., Hardy, C., et al. (2008). Identification of somatically acquired rearrangements in cancer using genome–wide massively parallel paired–end sequencing. Nat Genet 40, 722–729.Google Scholar
  29. Cardoso–Moreira, M., Arguello, J.R., Gottipati, S., Harshman, L.G., Grenier, J.K., and Clark, A.G. (2016). Evidence for the fixation of gene duplications by positive selection in Drosophila. Genome Res 26, 787–798.Google Scholar
  30. Carpenter, D., Dhar, S., Mitchell, L.M., Fu, B., Tyson, J., Shwan, N.A.A., Yang, F., Thomas, M.G., and Armour, J.A.L. (2015). Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes. Human Mol Genets 24, 3472–3480.Google Scholar
  31. Carvalho, C.M.B., and Lupski, J.R. (2016). Mechanisms underlying structural variant formation in genomic disorders. Nat Rev Genet 17, 224–238.Google Scholar
  32. Casola, C., Ganote, C.L., and Hahn, M.W. (2010). Nonallelic gene conversion in the genus Drosophila. Genetics 185, 95–103.Google Scholar
  33. Chaisson, M.J.P., Huddleston, J., Dennis, M.Y., Sudmant, P.H., Malig, M., Hormozdiari, F., Antonacci, F., Surti, U., Sandstrom, R., Boitano, M., et al. (2015a). Resolving the complexity of the human genome using single–molecule sequencing. Nature 517, 608–611.Google Scholar
  34. Chaisson, M.J.P., Wilson, R.K., and Eichler, E.E. (2015b). Genetic variation and the de novo assembly of human genomes. Nat Rev Genet 16, 627–640.Google Scholar
  35. Chakraborty, M., Baldwin–Brown, J.G., Long, A.D., and Emerson, J.J. (2016). Contiguous and accurate de novo assembly of metazoan genomes with modest long read coverage. Nucleic Acids Res 15, gkw654.Google Scholar
  36. Chakraborty, M., VanKuren, N.W., Zhao, R., Zhang, X., Kalsow, S., and Emerson, J.J. (2018). Hidden genetic variation shapes the structure of functional elements in Drosophila. Nat Genet 50, 20–25.Google Scholar
  37. Charrier, C., Joshi, K., Coutinho–Budd, J., Kim, J.E., Lambert, N., de Marchena, J., Jin, W.L., Vanderhaeghen, P., Ghosh, A., Sassa, T., et al. (2012). Inhibition of SRGAP2 function by its human–specific paralogs induces neoteny during spine maturation. Cell 149, 923–935.Google Scholar
  38. Chen, K., Wallis, J.W., McLellan, M.D., Larson, D.E., Kalicki, J.M., Pohl, C.S., McGrath, S.D., Wendl, M.C., Zhang, Q., Locke, D.P., et al. (2009). BreakDancer: an algorithm for high–resolution mapping of genomic structural variation. Nat Methods 6, 677–681.Google Scholar
  39. Chen, S., Krinsky, B.H., and Long, M. (2013). New genes as drivers of phenotypic evolution. Nat Rev Genet 14, 645–660.Google Scholar
  40. Chin, C.S., Alexander, D.H., Marks, P., Klammer, A.A., Drake, J., Heiner, C., Clum, A., Copeland, A., Huddleston, J., Eichler, E.E., et al. (2013). Nonhybrid, finished microbial genome assemblies from long–read SMRT sequencing data. Nat Methods 10, 563–569.Google Scholar
  41. Chin, C.S., Peluso, P., Sedlazeck, F.J., Nattestad, M., Concepcion, G.T., Clum, A., Dunn, C., O’Malley, R., Figueroa–Balderas, R., Morales–Cruz, A., et al. (2016). Phased diploid genome assembly with singlemolecule real–time sequencing. Nat Methods 13, 1050–1054.Google Scholar
  42. Chung, H., Bogwitz, M.R., McCart, C., Andrianopoulos, A., Ffrench–Constant, R.H., Batterham, P., and Daborn, P.J. (2007). Cis–regulatory elements in the Accord retrotransposon result in tissue–specific expression of the Drosophila melanogaster insecticide resistance gene Cyp6g1. Genetics 175, 1071–1077.Google Scholar
  43. Church, D.M., Goodstadt, L., Hillier, L.W., Zody, M.C., Goldstein, S., She, X., Bult, C.J., Agarwala, R., Cherry, J.L., DiCuccio, M., et al. (2009). Lineage–specific biology revealed by a finished genome assembly of the mouse. PLoS Biol 7, e1000112.Google Scholar
  44. Clarke, J., Wu, H.C., Jayasinghe, L., Patel, A., Reid, S., and Bayley, H. (2009). Continuous base identification for single–molecule nanopore DNA sequencing. Nat Nanotech 4, 265–270.Google Scholar
  45. Clifton, B.D., Librado, P., Yeh, S.D., Solares, E.S., Real, D.A., Jayasekera, S.U., Zhang, W., Shi, M., Park, R.V., Magie, R.D., et al. (2017). Rapid functional and sequence differentiation of a tandemly repeated speciesspecific multigene family in Drosophila. Mol Biol Evol 34, 51–65.Google Scholar
  46. Conrad, D.F., and Hurles, M.E. (2007). The population genetics of structural variation. Nat Genet 39, S30–S36.Google Scholar
  47. Conrad, D.F., Pinto, D., Redon, R., Feuk, L., Gokcumen, O., Zhang, Y., Aerts, J., Andrews, T.D., Barnes, C., Campbell, P., et al. (2010). Origins and functional impact of copy number variation in the human genome. Nature 464, 704–712.Google Scholar
  48. C. elegans Sequencing Consortium. (1998). Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282, 2012–2018.Google Scholar
  49. Deng, C., Cheng, C.H.C., Ye, H., He, X., and Chen, L. (2010). Evolution of an antifreeze protein by neofunctionalization under escape from adaptive conflict. Proc Natl Acad Sci USA 107, 21593–21598.Google Scholar
  50. Dennis, M.Y., Harshman, L., Nelson, B.J., Penn, O., Cantsilieris, S., Huddleston, J., Antonacci, F., Penewit, K., Denman, L., Raja, A., et al. (2017). The evolution and population diversity of human–specific segmental duplications. Nat ecol evol 1, 0069.Google Scholar
  51. Dennis, M.Y., Nuttle, X., Sudmant, P.H., Antonacci, F., Graves, T.A., Nefedov, M., Rosenfeld, J.A., Sajjadian, S., Malig, M., Kotkiewicz, H., et al. (2012). Evolution of human–specific neural SRGAP2 genes by incomplete segmental duplication. Cell 149, 912–922.Google Scholar
  52. Des Marais, D.L., and Rausher, M.D. (2008). Escape from adaptive conflict after duplication in an anthocyanin pathway gene. Nature 454, 762–765.Google Scholar
  53. Dopman, E.B., and Hartl, D.L. (2007). A portrait of copy–number polymorphism in Drosophila melanogaster. Proc Natl Acad Sci USA 104, 19920–19925.Google Scholar
  54. Dujon, B. (2010). Yeast evolutionary genomics. Nat Rev Genet 11, 512–524.Google Scholar
  55. Dunn, B., Richter, C., Kvitek, D.J., Pugh, T., and Sherlock, G. (2012). Analysis of the Saccharomyces cerevisiae pan–genome reveals a pool of copy number variants distributed in diverse yeast strains from differing industrial environments. Genome Res 22, 908–924.Google Scholar
  56. Earl, D., Bradnam, K., St. John, J., Darling, A., Lin, D., Fass, J., Yu, H.O. K., Buffalo, V., Zerbino, D.R., Diekhans, M., et al. (2011). Assemblathon 1: a competitive assessment of de novo short read assembly methods. Genome Res 21, 2224–2241.Google Scholar
  57. Eid, J., Fehr, A., Gray, J., Luong, K., Lyle, J., Otto, G., Peluso, P., Rank, D., Baybayan, P., Bettman, B., et al. (2009). Real–time DNA sequencing from single polymerase molecules. Science 323, 133–138.Google Scholar
  58. Eirin–Lopez, J.M., Rebordinos, L., Rooney, A.P., and Rozas, J. (2012). The birth–and–death evolution of multigene families revisited. Genome Dynam 7, 170–196.Google Scholar
  59. Emerson, J.J., Cardoso–Moreira, M., Borevitz, J.O., and Long, M. (2008). Natural selection shapes genome–wide patterns of copy–number polymorphism in Drosophila melanogaster. Science 320, 1629–1631.Google Scholar
  60. Ersfeld, K. (2004). Fiber–FISH: fluorescence in situ hybridization on stretched DNA. Methods Mol Biol 270, 395–402.Google Scholar
  61. Faucon, F., Dusfour, I., Gaude, T., Navratil, V., Boyer, F., Chandre, F., Sirisopa, P., Thanispong, K., Juntarajumnong, W., Poupardin, R., et al. (2015). Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing. Genome Res 25, 1347–1359.Google Scholar
  62. Fawcett, J.A., and Innan, H. (2015). Spreading good news. eLife 4, e07108.Google Scholar
  63. Feyereisen, R., Dermauw, W., and Van Leeuwen, T. (2015). Genotype to phenotype, the molecular and physiological dimensions of resistance in arthropods. Pesticide Biochem Physiol 121, 61–77.Google Scholar
  64. Fiddes, I.T., Lodewijk, G.A., Mooring, M., Bosworth, C.M., Ewing, A.D., Mantalas, G.L., Novak, A.M., van den Bout, A., Bishara, A., Rosenkrantz, J.L., et al. (2018). Human–specific NOTCH2NL genes affect Notch signaling and cortical neurogenesis. Cell 173, 1356–1369. e22.Google Scholar
  65. Florio, M., Albert, M., Taverna, E., Namba, T., Brandl, H., Lewitus, E., Haffner, C., Sykes, A., Wong, F.K., Peters, J., et al. (2015). Humanspecific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science 347, 1465–1470.Google Scholar
  66. Force, A., Lynch, M., Pickett, F.B., Amores, A., Yan, Y.L., and Postlethwait, J. (1999). Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151, 1531–1545.Google Scholar
  67. Francino, M.P. (2005). An adaptive radiation model for the origin of new gene functions. Nat Genet 37, 573–578.Google Scholar
  68. Gabrieli, T., Sharim, H., Fridman, D., Arbib, N., Michaeli, Y., and Ebenstein, Y. (2018). Selective nanopore sequencing of human BRCA1 by Cas9–assisted targeting of chromosome segments (CATCH). Nucleic Acids Res 46, e87.Google Scholar
  69. Gao, L.Z., and Innan, H. (2004). Very low gene duplication rate in the yeast genome. Science 306, 1367–1370.Google Scholar
  70. Gnerre, S., Maccallum, I., Przybylski, D., Ribeiro, F.J., Burton, J.N., Walker, B.J., Sharpe, T., Hall, G., Shea, T.P., Sykes, S., et al. (2011). High–quality draft assemblies of mammalian genomes from massively parallel sequence data. Proc Natl Acad Sci USA 108, 1513–1518.Google Scholar
  71. Golicz, A.A., Batley, J., and Edwards, D. (2016). Towards plant pangenomics. Plant Biotechnol J 14, 1099–1105.Google Scholar
  72. Green, P. (1997). Against a whole–genome shotgun. Genome Res 7, 410–417.Google Scholar
  73. Gu, W., Zhang, F., and Lupski, J.R. (2008). Mechanisms for human genomic rearrangements. PathoGenetics 1, 4.Google Scholar
  74. Gu, Z., Steinmetz, L.M., Gu, X., Scharfe, C., Davis, R.W., and Li, W.H. (2003). Role of duplicate genes in genetic robustness against null mutations. Nature 421, 63–66.Google Scholar
  75. Guillemaud, T., Lenormand, T., Bourguet, D., Chevillon, C., Pateur, N., and Raymond, M. (1998). Evolution of resistance in Culex pipiens: allele replacemente and changing environment. Evolution 52, 443–453.Google Scholar
  76. Gurevich, A., Saveliev, V., Vyahhi, N., and Tesler, G. (2013). QUAST: quality assessment tool for genome assemblies. Bioinformatics 29, 1072–1075.Google Scholar
  77. Hahn, M.W. (2009). Distinguishing among evolutionary models for the maintenance of gene duplicates. J Hered 100, 605–617.Google Scholar
  78. Hahn, M.W., Han, M.V., and Han, S.G. (2007). Gene family evolution across 12 Drosophila genomes. PLoS Genet 3, e197.Google Scholar
  79. Harewood, L., Chaignat, E., and Alexandre., R. (2012). Structural variation and its effects on expresson. Methods Mol Biol 838, 173–186.Google Scholar
  80. Hastings, P.J., Lupski, J.R., Rosenberg, S.M., and Ira, G. (2009). Mechanisms of change in gene copy number. Nat Rev Genet 10, 551–564.Google Scholar
  81. Hemingway, J., Hawkes, N.J., McCarroll, L., and Ranson, H. (2004). The molecular basis of insecticide resistance in mosquitoes. Insect Biochem Mol Biol 34, 653–665.Google Scholar
  82. Hendrickson, H., Slechta, E.S., Bergthorsson, U., Andersson, D.I., and Roth, J.R. (2002). Amplification–mutagenesis: Evidence that “directed” adaptive mutation and general hypermutability result from growth with a selected gene amplification. Proc Natl Acad Sci USA 99, 2164–2169.Google Scholar
  83. Hindson, B.J., Ness, K.D., Masquelier, D.A., Belgrader, P., Heredia, N.J., Makarewicz, A.J., Bright, I.J., Lucero, M.Y., Hiddessen, A.L., Legler, T.C., et al. (2011). High–throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem 83, 8604–8610.Google Scholar
  84. Hollox, E.J. (2008). Copy number variation of beta–defensins and relevance to disease. Cytogenet Genome Res 123, 148–155.Google Scholar
  85. Hollox, E.J. (2012). The challenges of studying complex and dynamic regions of the human genome. Methods Mol Biol 838, 187–207.Google Scholar
  86. Hollox, E.J., and Abujaber, R. (2017). Evolution and diversity of defensins in vertebrates. In Evolutionary Biology: Self/Nonself Evolution, Species and Complex Traits Evolution, Methods and Concepts, P. Pontarotti, ed. (Cham, Switzerland: Springer), pp. 27–50.Google Scholar
  87. Hollox, E.J., Barber, J.C.K., Brookes, A.J., and Armour, J.A.L. (2008a). Defensins and the dynamic genome: What we can learn from structural variation at human chromosome band 8p23.1. Genome Res 18, 1686–1697.Google Scholar
  88. Hollox, E.J., Huffmeier, U., Zeeuwen, P.L.J.M., Palla, R., Lascorz, J., Rodijk–Olthuis, D., van de Kerkhof, P.C.M., Traupe, H., de Jongh, G., den Heijer, M., et al. (2008b). Psoriasis is associated with increased β–defensin genomic copy number. Nat Genet 40, 23–25.Google Scholar
  89. Hormozdiari, F., Alkan, C., Eichler, E.E., and Sahinalp, S.C. (2009). Combinatorial algorithms for structural variation detection in highthroughput sequenced genomes. Genome Res 19, 1270–1278.Google Scholar
  90. Hoskins, R.A., Carlson, J.W., Kennedy, C., Acevedo, D., Evans–Holm, M., Frise, E., Wan, K.H., Park, S., Mendez–Lago, M., Rossi, F., et al. (2007). Sequence finishing and mapping of Drosophila melanogaster heterochromatin. Science 316, 1625–1628.Google Scholar
  91. Huddleston, J., and Eichler, E.E. (2016). An incomplete understanding of human genetic variation. Genetics 202, 1251–1254.Google Scholar
  92. Huddleston, J., Ranade, S., Malig, M., Antonacci, F., Chaisson, M., Hon, L., Sudmant, P.H., Graves, T.A., Alkan, C., Dennis, M.Y., et al. (2014). Reconstructing complex regions of genomes using long–read sequencing technology. Genome Res 24, 688–696.Google Scholar
  93. Hughes, A.L. (1994). The evolution of functionally novel proteins after gene duplication. Proc R Soc Lond B 256, 119–124.Google Scholar
  94. Innan, H. (2003). A two–locus gene conversion model with selection and its application to the human RHCE and RHD genes. Proc Natl Acad Sci USA 100, 8793–8798.Google Scholar
  95. Innan, H. (2009). Population genetic models of duplicated genes. Genetica 137, 19–37.Google Scholar
  96. Innan, H., and Kondrashov, F. (2010). The evolution of gene duplications: classifying and distinguishing between models. Nat Rev Genet 11, 97–108.Google Scholar
  97. Iqbal, Z., Caccamo, M., Turner, I., Flicek, P., and McVean, G. (2012). De novo assembly and genotyping of variants using colored de Bruijn graphs. Nat Genet 44, 226–232.Google Scholar
  98. Istrail, S., Sutton, G.G., Florea, L., Halpern, A.L., Mobarry, C.M., Lippert, R., Walenz, B., Shatkay, H., Dew, I., Miller, J.R., et al. (2004). Wholegenome shotgun assembly and comparison of human genome assemblies. Proc Natl Acad Sci USA 101, 1916–1921.Google Scholar
  99. James, C.P., Bajaj–Elliott, M., Abujaber, R., Forya, F., Klein, N., David, A. L., Hollox, E.J., and Peebles, D.M. (2018). Human beta defensin (HBD) gene copy number affects HBD2 protein levels: impact on cervical bactericidal immunity in pregnancy. Eur J Hum Genet 26, 434–439.Google Scholar
  100. Jayaswal, V., Jimenez, J., Magie, R., Nguyen, K., Clifton, B., Yeh, S., and Ranz, J.M. (2018). A species–specific multigene family mediates differential sperm displacement in Drosophila melanogaster. Evolution 72, 399–403.Google Scholar
  101. Jiang, W., Johnson, C., Jayaraman, J., Simecek, N., Noble, J., Moffatt, M. F., Cookson, W.O., Trowsdale, J., and Traherne, J.A. (2012a). Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors. Genome Res 22, 1845–1854.Google Scholar
  102. Jiang, W., Johnson, C., Simecek, N., López–Álvarez, M.R., Di, D., Trowsdale, J., and Traherne, J.A. (2016). qKAT: a high–throughput qPCR method for KIR gene copy number and haplotype determination. Genome Med 8, 99.Google Scholar
  103. Jiang, W., Zhao, X., Gabrieli, T., Lou, C., Ebenstein, Y., and Zhu, T.F. (2015). Cas9–assisted targeting of chromosome segments CATCH enables one–step targeted cloning of large gene clusters. Nat Commun 6, 8101.Google Scholar
  104. Jiang, Y., Wang, Y., and Brudno, M. (2012b). PRISM: pair–read informed split–read mapping for base–pair level detection of insertion, deletion and structural variants. Bioinformatics 28, 2576–2583.Google Scholar
  105. Jugulam, M., Niehues, K., Godar, A.S., Koo, D.H., Danilova, T., Friebe, B., Sehgal, S., Varanasi, V.K., Wiersma, A., Westra, P., et al. (2014). Tandem amplification of a chromosomal segment harboring 5–enolpyruvylshikimate–3–phosphate synthase locus confers glyphosate resistance in Kochia scoparia. Plant Physiol 166, 1200–1207.Google Scholar
  106. Kaessmann, H. (2010). Origins, evolution, and phenotypic impact of new genes. Genome Res 20, 1313–1326.Google Scholar
  107. Kajitani, R., Toshimoto, K., Noguchi, H., Toyoda, A., Ogura, Y., Okuno, M., Yabana, M., Harada, M., Nagayasu, E., Maruyama, H., et al. (2014). Efficient de novo assembly of highly heterozygous genomes from whole–genome shotgun short reads. Genome Res 24, 1384–1395.Google Scholar
  108. Katju, V. (2012). In with the old, in with the new: the promiscuity of the duplication process engenders diverse pathways for novel gene creation. Int J Evol Biol 2012(2), 1–24.Google Scholar
  109. Katju, V., and Bergthorsson, U. (2013). Copy–number changes in evolution: rates, fitness effects and adaptive significance. Front Genet 4, 273.Google Scholar
  110. Kondrashov, F.A. (2010). Gene dosage and duplication. In Evolution after Gene Duplication, K. Dittmar, and D. Liberles, ed. (Wiley–Blackwell), pp. 57–76.Google Scholar
  111. Kondrashov, F.A. (2012). Gene duplication as a mechanism of genomic adaptation to a changing environment. Proc R Soc B–Biol Sci 279, 5048–5057.Google Scholar
  112. Korbel, J.O., Abyzov, A., Mu, X.J., Carriero, N., Cayting, P., Zhang, Z., Snyder, M., and Gerstein, M.B. (2009). PEMer: a computational framework with simulation–based error models for inferring genomic structural variants from massive paired–end sequencing data. Genome Biol 10, R23.Google Scholar
  113. Korbel, J.O., Urban, A.E., Affourtit, J.P., Godwin, B., Grubert, F., Simons, J.F., Kim, P.M., Palejev, D., Carriero, N.J., Du, L., et al. (2007). Pairedend mapping reveals extensive structural variation in the human genome. Science 318, 420–426.Google Scholar
  114. Koren, S., Schatz, M.C., Walenz, B.P., Martin, J., Howard, J.T., Ganapathy, G., Wang, Z., Rasko, D.A., McCombie, W.R., Jarvis, E.D., et al. (2012). Hybrid error correction and de novo assembly of single–molecule sequencing reads. Nat Biotechnol 30, 693–700.Google Scholar
  115. Koren, S., Walenz, B.P., Berlin, K., Miller, J.R., Bergman, N.H., and Phillippy, A.M. (2017). Canu: scalable and accurate long–read assembly via adaptive k–mer weighting and repeat separation. Genome Res 27, 722–736.Google Scholar
  116. Krsticevic, F.J., Schrago, C.G., and Carvalho, A.B. (2015). Long–read single molecule sequencing to resolve tandem gene copies: The Mst77Y region on the Drosophila melanogaster Y chromosome. G3 5, 1145–1150.Google Scholar
  117. Kulathinal, R.J., Sawyer, S.A., Bustamante, C.D., Nurminsky, D., Ponce, R., Ranz, J.M., and Hartl, D.L. (2004). Selective sweep in the evolution of a new sperm–specific gene in Drosophila. In Selective Sweep, D. Nurminsky, ed. (Austin, Texas: Kluwer Academic/Plenum Publishers), pp. 1–12.Google Scholar
  118. Kurtz, S., Phillippy, A., Delcher, A.L., Smoot, M., Shumway, M., Antonescu, C., and Salzberg, S.L. (2004). Versatile and open software for comparing large genomes.. Genome Biol 5, R12.Google Scholar
  119. Labbé, P., Berthomieu, A., Berticat, C., Alout, H., Raymond, M., Lenormand, T., and Weill, M. (2007). Independent duplications of the acetylcholinesterase gene conferring insecticide resistance in the mosquito Culex pipiens. Mol Biol Evol 24, 1056–1067.Google Scholar
  120. Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., Baldwin, J., Devon, K., Dewar, K., Doyle, M., FitzHugh, W., et al. (2001). Initial sequencing and analysis of the human genome. Nature 409, 860–921.Google Scholar
  121. Layer, R.M., Chiang, C., Quinlan, A.R., and Hall, I.M. (2014). LUMPY: a probabilistic framework for structural variant discovery. Genome Biol 15, R84.Google Scholar
  122. Li, H. (2016). Minimap and miniasm: fast mapping and de novo assembly for noisy long sequences. Bioinformatics 32, 2103–2110.Google Scholar
  123. Lin, Y., Yuan, J., Kolmogorov, M., Shen, M.W., Chaisson, M., and Pevzner, P.A. (2016). Assembly of long error–prone reads using de Bruijn graphs. Proc Natl Acad Sci USA 113, e8396–E8405.Google Scholar
  124. Livak, K.J., and Schmittgen, T.D. (2001). Analysis of relative gene expression data using real–time quantitative PCR and the 2−ΔΔCT method. Methods 25, 402–408.Google Scholar
  125. Long, M., VanKuren, N.W., Chen, S., and Vibranovski, M.D. (2013). New gene evolution: little did we know. Annu Rev Genet 47, 307–333.Google Scholar
  126. Luo, R., Liu, B., Xie, Y., Li, Z., Huang, W., Yuan, J., He, G., Chen, Y., Pan, Q., Liu, Y., et al. (2012). SOAPdenovo2: an empirically improved memory–efficient short–read de novo assembler. GigaScience 1, 18.Google Scholar
  127. Lupski, J.R. (1998). Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genets 14, 417–422.Google Scholar
  128. Lupski, J.R., and Stankiewicz, P. (2005). Genomic disorders: Molecular mechanisms for rearrangements and conveyed phenotypes. PLoS Genet 1, e49–633.Google Scholar
  129. Mardis, E.R. (2013). Next–generation sequencing platforms. Annu Rev Anal Chem 6, 287–303.Google Scholar
  130. Margulies, M., Egholm, M., Altman, W.E., Attiya, S., Bader, J.S., Bemben, L.A., Berka, J., Braverman, M.S., Chen, Y.J., Chen, Z., et al. (2005). Genome sequencing in microfabricated high–density picolitre reactors. Nature 437, 376–380.Google Scholar
  131. Marques–Bonet, T., Girirajan, S., and Eichler, E.E. (2009). The origins and impact of primate segmental duplications. Trends Genets 25, 443–454.Google Scholar
  132. Martin, M.P., Bashirova, A., Traherne, J., Trowsdale, J., and Carrington, M. (2003). Cutting edge: Expansion of the KIR locus by unequal crossing over. J Immunol 171, 2192–2195.Google Scholar
  133. Martins, W.F.S., Subramaniam, K., Steen, K., Mawejje, H., Liloglou, T., Donnelly, M.J., and Wilding, C.S. (2017). Detection and quantitation of copy number variation in the voltage–gated sodium channel gene of the mosquito Culex quinquefasciatus. Sci Rep 7, 5821.Google Scholar
  134. McCoy, R.C., Taylor, R.W., Blauwkamp, T.A., Kelley, J.L., Kertesz, M., Pushkarev, D., Petrov, D.A., and Fiston–Lavier, A.S. (2014). Illumina TruSeq synthetic long–reads empower de novo assembly and resolve complex, highly–repetitive transposable elements. PLoS ONE 9, e106689.Google Scholar
  135. McKernan, K.J., Peckham, H.E., Costa, G.L., McLaughlin, S.F., Fu, Y., Tsung, E.F., Clouser, C.R., Duncan, C., Ichikawa, J.K., Lee, C.C., et al. (2009). Sequence and structural variation in a human genome uncovered by short–read, massively parallel ligation sequencing using two–base encoding. Genome Res 19, 1527–1541.Google Scholar
  136. Medvedev, P., Stanciu, M., and Brudno, M. (2009). Computational methods for discovering structural variation with next–generation sequencing. Nat Methods 6, S13–S20.Google Scholar
  137. Miller, J.R., Zhou, P., Mudge, J., Gurtowski, J., Lee, H., Ramaraj, T., Walenz, B.P., Liu, J., Stupar, R.M., Denny, R., et al. (2017). Hybrid assembly with long and short reads improves discovery of gene family expansions. BMC Genomics 18, 541.Google Scholar
  138. Mohajeri, K., Cantsilieris, S., Huddleston, J., Nelson, B.J., Coe, B.P., Campbell, C.D., Baker, C., Harshman, L., Munson, K.M., Kronenberg, Z.N., et al. (2016). Interchromosomal core duplicons drive both evolutionary instability and disease susceptibility of the Chromosome 8p23.1 region. Genome Res 26, 1453–1467.Google Scholar
  139. Mouches, C., Pasteur, N., Berge, J.B., Hyrien, O., Raymond, M., de Saint Vincent, B.R., de Silvestri, M., and Georghiou, G.P. (1986). Amplification of an esterase gene is responsible for insecticide resistance in a California Culex mosquito. Science 233, 778–780.Google Scholar
  140. Waterston, R.H., Lindblad–Toh, K., Birney, E., Rogers, J., Abril, J.F., Agarwal, P., Agarwala, R., Ainscough, R., Alexandersson, M., et al. (2002). Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562.Google Scholar
  141. Myers, E.W., Sutton, G.G., Delcher, A.L., Dew, I.M., Fasulo, D.P., Flanigan, M.J., Kravitz, S.A., Mobarry, C.M., Reinert, K.H.J., Remington, K.A., et al. (2000). A whole–genome assembly of Drosophila. Science 287, 2196–2204.Google Scholar
  142. Nagylaki, T., and Petes, T.D. (1982). Intrachromosomal gene conversion and the maintenance of sequence homogeneity among repeated genes. Genetics 100, 315–337.Google Scholar
  143. Näsvall, J., Sun, L., Roth, J.R., and Andersson, D.I. (2012). Real–time evolution of new genes by innovation, amplification, and divergence. Science 338, 384–387.Google Scholar
  144. Nei, M., and Rooney, A.P. (2005). Concerted and birth–and–death evolution of multigene families. Annu Rev Genet 39, 121–152.Google Scholar
  145. Nguyen, D.Q., Webber, C., Hehir–Kwa, J., Pfundt, R., Veltman, J., and Ponting, C.P. (2008). Reduced purifying selection prevails over positive selection in human copy number variant evolution. Genome Res 18, 1711–1723.Google Scholar
  146. Nguyen, H.T., Boocock, J., Merriman, T.R., and Black, M.A. (2016). SRBreak: A read–depth and split–read framework to identify breakpoints of different events inside simple copy–number variable regions. Front Genet 7, 160.Google Scholar
  147. Nijkamp, J.F., van den Broek, M.A., Geertman, J.M.A., Reinders, M.J.T., Daran, J.M.G., and de Ridder, D. (2012). De novo detection of copy number variation by co–assembly. Bioinformatics 28, 3195–3202.Google Scholar
  148. Nurminsky, D., De Aguiar, D., Bustamante, C.D., and Hartl, D.L. (2001). Chromosomal effects of rapid gene evolution in Drosophila melanogaster. Science 291, 128–130.Google Scholar
  149. Nurminsky, D.I., Nurminskaya, M.V., De Aguiar, D., and Hartl, D.L. (1998). Selective sweep of a newly evolved sperm–specific gene in Drosophila. Nature 396, 572–575.Google Scholar
  150. Nuttle, X., Giannuzzi, G., Duyzend, M.H., Schraiber, J.G., Narvaiza, I., Sudmant, P.H., Penn, O., Chiatante, G., Malig, M., Huddleston, J., et al. (2016). Emergence of a Homo sapiens–specific gene family and chromosome 16p11.2 CNV susceptibility. Nature 536, 205–209.Google Scholar
  151. Nuttle, X., Huddleston, J., O’Roak, B.J., Antonacci, F., Fichera, M., Romano, C., Shendure, J., and Eichler, E.E. (2013). Rapid and accurate large–scale genotyping of duplicated genes and discovery of interlocus gene conversions. Nat Meth 10, 903–909.Google Scholar
  152. O’Roak, B.J., Vives, L., Fu, W., Egertson, J.D., Stanaway, I.B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., et al. (2012). Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science 338, 1619–1622.Google Scholar
  153. Obbard, D.J., Maclennan, J., Kim, K.W., Rambaut, A., O’Grady, P.M., and Jiggins, F.M. (2012). Estimating divergence dates and substitution rates in the Drosophila phylogeny. Mol Biol Evol 29, 3459–3473.Google Scholar
  154. Ohno, S. (1970). Evolution by Gene Duplication (New York: Springer–Verlag).Google Scholar
  155. Ohta, T. (1982). Allelic and nonallelic homology of a supergene family.. Proc Natl Acad Sci USA 79, 3251–3254.Google Scholar
  156. Osada, N., and Innan, H. (2008). Duplication and gene conversion in the Drosophila melanogaster genome. PLoS Genet 4, e1000305.Google Scholar
  157. Owen, R.P., Sangkuhl, K., Klein, T.E., and Altman, R.B. (2009). Cytochrome P450 2D6. Pharmacogenet Genomics 19, 559–562.Google Scholar
  158. Parham, P. (2005). Influence of KIR diversity on human immunity. Adv Exp Med Biol 560, 47–50.Google Scholar
  159. Parham, P., Norman, P.J., Abi–Rached, L., and Guethlein, L.A. (2012). Human–specific evolution of killer cell immunoglobulin–like receptor recognition of major histocompatibility complex class I molecules. Philos Trans R Soc B–Biol Sci 367, 800–811.Google Scholar
  160. Parra, G., Bradnam, K., and Korf, I. (2007). CEGMA: a pipeline to accurately annotate core genes in eukaryotic genomes. Bioinformatics 23, 1061–1067.Google Scholar
  161. Perry, G.H., Dominy, N.J., Claw, K.G., Lee, A.S., Fiegler, H., Redon, R., Werner, J., Villanea, F.A., Mountain, J.L., Misra, R., et al. (2007). Diet and the evolution of human amylase gene copy number variation. Nat Genet 39, 1256–1260.Google Scholar
  162. Pillai, S., Gopalan, V., and Lam, A.K.Y. (2017). Review of sequencing platforms and their applications in phaeochromocytoma and paragangliomas. Crit Rev Oncol/Hematol 116, 58–67.Google Scholar
  163. Pinheiro, L.B., Coleman, V.A., Hindson, C.M., Herrmann, J., Hindson, B. J., Bhat, S., and Emslie, K.R. (2012). Evaluation of a droplet digital polymerase chain reaction format for DNA copy number quantification. Anal Chem 84, 1003–1011.Google Scholar
  164. Pirooznia, M., Goes, F.S., and Zandi, P.P. (2015). Whole–genome CNV analysis: advances in computational approaches. Front Genet 06, 138.Google Scholar
  165. Ponce, R., and Hartl, D.L. (2006). The evolution of the novel Sdic gene cluster in Drosophila melanogaster. Gene 376, 174–183.Google Scholar
  166. Ponchel, F., Toomes, C., Bransfield, K., Leong, F.T., Douglas, S.H., Field, S.L., Bell, S.M., Combaret, V., Puisieux, A., Mighell, A.J., et al. (2003). Real–time PCR based on SYBR–Green I fluorescence: an alternative to the TaqMan assay for a relative quantification of gene rearrangements, gene amplifications and micro gene deletions.. BMC Biotechnol 3, 18.Google Scholar
  167. Pyo, C.W., Wang, R., Vu, Q., Cereb, N., Yang, S.Y., Duh, F.M., Wolinsky, S., Martin, M.P., Carrington, M., and Geraghty, D.E. (2013). Recombinant structures expand and contract inter and intragenic diversification at the KIR locus. BMC Genomics 14, 89.Google Scholar
  168. Ranz, J.M., and Parsch, J. (2012). Newly evolved genes: moving from comparative genomics to functional studies in model systems. Bioessays 34, 477–483.Google Scholar
  169. Ranz, J.M., Ponce, A.R., Hartl, D.L., and Nurminsky, D. (2003). Origin and evolution of a new gene expressed in the Drosophila sperm axoneme. Genetica 118, 233–244.Google Scholar
  170. Rausch, T., Zichner, T., Schlattl, A., Stütz, A.M., Benes, V., and Korbel, J. O. (2012). DELLY: structural variant discovery by integrated pairedend and split–read analysis. Bioinformatics 28, i333–i339.Google Scholar
  171. Raymond, M., Poulin, E., Boiroux, V., Dupont, E., and Pasteur, N. (1993). Stability of insecticide resistance due to amplification of esterase genes in Culex pipiens. Heredity 70, 301–307.Google Scholar
  172. Redon, R., Ishikawa, S., Fitch, K.R., Feuk, L., Perry, G.H., Andrews, T.D., Fiegler, H., Shapero, M.H., Carson, A.R., Chen, W., et al. (2006). Global variation in copy number in the human genome. Nature 444, 444–454.Google Scholar
  173. Reisner, W., Larsen, N.B., Silahtaroglu, A., Kristensen, A., Tommerup, N., Tegenfeldt, J.O., and Flyvbjerg, H. (2010). Single–molecule denaturation mapping of DNA in nanofluidic channels. Proc Natl Acad Sci USA 107, 13294–13299.Google Scholar
  174. Remnant, E.J., Good, R.T., Schmidt, J.M., Lumb, C., Robin, C., Daborn, P. J., and Batterham, P. (2013). Gene duplication in the major insecticide target site, Rdl, in Drosophila melanogaster. Proc Natl Acad Sci USA 110, 14705–14710.Google Scholar
  175. Ritz, A., Bashir, A., Sindi, S., Hsu, D., Hajirasouliha, I., and Raphael, B.J. (2014). Characterization of structural variants with single molecule and hybrid sequencing approaches. Bioinformatics 30, 3458–3466.Google Scholar
  176. Rodrigo, G., and Fares, M.A. (2018). Intrinsic adaptive value and early fate of gene duplication revealed by a bottom–up approach. eLife 7, e29739.Google Scholar
  177. Rogers, R.L., Bedford, T., and Hartl, D.L. (2009). Formation and longevity of chimeric and duplicate genes in Drosophila melanogaster. Genetics 181, 313–322.Google Scholar
  178. Rogers, R.L., Cridland, J.M., Shao, L., Hu, T.T., Andolfatto, P., and Thornton, K.R. (2014). Landscape of standing variation for tandem duplications in Drosophila yakuba and Drosophila simulans. Mol Biol Evol 31, 1750–1766.Google Scholar
  179. Salzberg, S.L., Phillippy, A.M., Zimin, A., Puiu, D., Magoc, T., Koren, S., Treangen, T.J., Schatz, M.C., Delcher, A.L., Roberts, M., et al. (2012). GAGE: A critical evaluation of genome assemblies and assembly algorithms. Genome Res 22, 557–567.Google Scholar
  180. Sedlazeck, F.J., Rescheneder, P., Smolka, M., Fang, H., Nattestad, M., von Haeseler, A., and Schatz, M.C. (2018). Accurate detection of complex structural variations using single–molecule sequencing. Nat Methods 15, 461–468.Google Scholar
  181. She, X., Liu, G., Ventura, M., Zhao, S., Misceo, D., Roberto, R., Cardone, M.F., Rocchi, M., Rocchi, M., Green, E.D., et al. (2006). A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a great–ape expansion of intrachromosomal duplications. Genome Res 16, 576–583.Google Scholar
  182. Simão, F.A., Waterhouse, R.M., Ioannidis, P., Kriventseva, E.V., and Zdobnov, E.M. (2015). BUSCO: assessing genome assembly and annotation completeness with single–copy orthologs. Bioinformatics 31, 3210–3212.Google Scholar
  183. Sindi, S.S., Onal, S., Peng, L.C., Wu, H.T., and Raphael, B.J. (2012). An integrative probabilistic model for identification of structural variation in sequencing data. Genome Biol 13, R22.Google Scholar
  184. Spofford, J.B. (1969). Heterosis and the evolution of duplications. Am Natist 103, 407–432.Google Scholar
  185. Stancu, M.C., van Roosmalen, M.J., Renkens, I., Nieboer, M.M., Middelkamp, S., de Ligt, J., Pregno, G., Giachino, D., Mandrile, G., Espejo Valle–Inclan, J., et al. (2017). Mapping and phasing of structural variation in patient genomes using nanopore sequencing. Nat Commun 8, 1326.Google Scholar
  186. Staňková, H., Hastie, A.R., Chan, S., Vrána, J., Tulpová, Z., Kubaláková, M., Visendi, P., Hayashi, S., Luo, M., Batley, J., et al. (2016). BioNano genome mapping of individual chromosomes supports physical mapping and sequence assembly in complex plant genomes. Plant Biotechnol J 14, 1523–1531.Google Scholar
  187. Stranger, B.E., Forrest, M.S., Dunning, M., Ingle, C.E., Beazley, C., Thorne, N., Redon, R., Bird, C.P., de Grassi, A., Lee, C., et al. (2007). Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315, 848–853.Google Scholar
  188. Sudmant, P.H., Rausch, T., Gardner, E.J., Handsaker, R.E., Abyzov, A., Huddleston, J., Zhang, Y., Ye, K., Jun, G., Hsi–Yang Fritz, M., et al. (2015). An integrated map of structural variation in 2,504 human genomes. Nature 526, 75–81.Google Scholar
  189. Tettelin, H., Masignani, V., Cieslewicz, M.J., Donati, C., Medini, D., Ward, N.L., Angiuoli, S.V., Crabtree, J., Jones, A.L., Durkin, A.S., et al. (2005). Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: Implications for the microbial “pangenome”. Proc Natl Acad Sci USA 102, 13950–13955.Google Scholar
  190. Traherne, J.A., Martin, M., Ward, R., Ohashi, M., Pellett, F., Gladman, D., Middleton, D., Carrington, M., and Trowsdale, J. (2010). Mechanisms of copy number variation and hybrid gene formation in the KIR immune gene complex. Human Mol Genets 19, 737–751.Google Scholar
  191. Trappe, K., Emde, A.K., Ehrlich, H.C., and Reinert, K. (2014). Gustaf: Detecting and correctly classifying SVs in the NGS twilight zone. Bioinformatics 30, 3484–3490.Google Scholar
  192. Traut, W., Rahn, I.M., Winking, H., Kunze, B., and Weichenhan, D. (2001). Evolution of a 6–20. Mb long–range repeat cluster in the genus Mus. Chromosoma 110, 247–252.Google Scholar
  193. VanKuren, N.W., and Long, M. (2018). Gene duplicates resolving sexual conflict rapidly evolved essential gametogenesis functions. Nat Ecol Evol 2, 705–712.Google Scholar
  194. Veitia, R.A. (2002). Exploring the etiology of haploinsufficiency. Bioessays 24, 175–184.Google Scholar
  195. Venter, J.C., Adams, M.D., Myers, E.W., Li, P.W., Mural, R.J., Sutton, G. G., Smith, H.O., Yandell, M., Evans, C.A., Holt, R.A., et al. (2001). The sequence of the human genome. Science 291, 1304–1351.Google Scholar
  196. Voskoboynik, A., Neff, N.F., Sahoo, D., Newman, A.M., Pushkarev, D., Koh, W., Passarelli, B., Fan, H.C., Mantalas, G.L., Palmeri, K.J., et al. (2013). The genome sequence of the colonial chordate, Botryllus schlosseri. eLife 2, e00569.Google Scholar
  197. Walker, B.J., Abeel, T., Shea, T., Priest, M., Abouelliel, A., Sakthikumar, S., Cuomo, C.A., Zeng, Q., Wortman, J., Young, S.K., et al. (2014). Pilon: an integrated tool for comprehensive microbial variant detection and genome assembly improvement. PLoS ONE 9, e112963.Google Scholar
  198. Walsh, J.B. (1987). Sequence–dependent gene conversion: can duplicated genes diverge fast enough to escape conversion? Genetics 117, 543–557.Google Scholar
  199. Weber, J.L., and Myers, E.W. (1997). Human whole–genome shotgun sequencing. Genome Res 7, 401–409.Google Scholar
  200. Weichenhan, D., Kunze, B., Winking, H., van Geel, M., Osoegawa, K., de Jong, P.J., and Traut, W. (2001). Source and component genes of a 6–20. Mb gene cluster in the house mouse. Mamm Genome 12, 590–594.Google Scholar
  201. Wondji, C.S., Irving, H., Morgan, J., Lobo, N.F., Collins, F.H., Hunt, R.H., Coetzee, M., Hemingway, J., and Ranson, H. (2009). Two duplicated P450 genes are associated with pyrethroid resistance in Anopheles funestus, a major malaria vector. Genome Res 19, 452–459.Google Scholar
  202. Xi, R., Hadjipanayis, A.G., Luquette, L.J., Kim, T.M., Lee, E., Zhang, J., Johnson, M.D., Muzny, D.M., Wheeler, D.A., Gibbs, R.A., et al. (2011). Copy number variation detection in whole–genome sequencing data using the Bayesian information criterion. Proc Natl Acad Sci USA 108, e1128–E1136.Google Scholar
  203. Xie, C., and Tammi, M.T. (2009). CNV–seq, a new method to detect copy number variation using high–throughput sequencing. BMC BioInf 10, 80.Google Scholar
  204. Yao, R., Zhang, C., Yu, T., Li, N., Hu, X., Wang, X., Wang, J., and Shen, Y. (2017). Evaluation of three read–depth based CNV detection tools using whole–exome sequencing data. Mol Cytogenet 10, 30.Google Scholar
  205. Ye, C., Hill, C.M., Wu, S., Ruan, J., and Ma, Z.S. (2016). DBG2OLC: Efficient assembly of large genomes using long erroneous reads of the third generation sequencing technologies. Sci Rep 6, 31900.Google Scholar
  206. Ye, K., Schulz, M.H., Long, Q., Apweiler, R., and Ning, Z. (2009). Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired–end short reads. Bioinformatics 25, 2865–2871.Google Scholar
  207. Yeh, S.D., Do, T., Abbassi, M., and Ranz, J.M. (2012a). Functional relevance of the newly evolved sperm dynein intermediate chain multigene family in Drosophila melanogaster males. Commun Integrat Biol 5, 462–465.Google Scholar
  208. Yeh, S.D., Do, T., Chan, C., Cordova, A., Carranza, F., Yamamoto, E.A., Abbassi, M., Gandasetiawan, K.A., Librado, P., Damia, E., et al. (2012b). Functional evidence that a recently evolved Drosophila sperm-specific gene boosts sperm competition. Proc Natl Acad Sci USA 109, 2043–2048.Google Scholar
  209. Yoon, S., Xuan, Z., Makarov, V., Ye, K., and Sebat, J. (2009). Sensitive and accurate detection of copy number variants using read depth of coverage. Genome Res 19, 1586–1592.Google Scholar
  210. Zhang, B., Sambono, J.L., Morgan, J.A.T., Venus, B., Rolls, P., and Lew–Tabor, A.E. (2016). An evaluation of quantitative PCR assays (TaqMan® and SYBR Green) for the detection of Babesia bigemina and Babesia bovis, and a novel fluorescent–ITS1–PCR capillary electrophoresis method for genotyping B. bovis isolates. Vet Sci 3, 23.Google Scholar
  211. Zhang, F., Carvalho, C.M.B., and Lupski, J.R. (2009). Complex human chromosomal and genomic rearrangements. Trends Genets 25, 298–307.Google Scholar
  212. Zhang, J., Wang, J., and Wu, Y. (2012). An improved approach for accurate and efficient calling of structural variations with low–coverage sequence data. BMC BioInf 13, S6.Google Scholar
  213. Zhang, Z.D., Du, J., Lam, H., Abyzov, A., Urban, A.E., Snyder, M., and Gerstein, M. (2011). Identification of genomic indels and structural variations using split reads. BMC Genomics 12, 375.Google Scholar
  214. Zhao, M., Wang, Q., Wang, Q., Jia, P., and Zhao, Z. (2013). Computational tools for copy number variation (CNV) detection using next–generation sequencing data: features and perspectives. BMC BioInf 14, S1.Google Scholar
  215. Zhao, Q., Feng, Q., Lu, H., Li, Y., Wang, A., Tian, Q., Zhan, Q., Lu, Y., Zhang, L., Huang, T., et al. (2018). Pan–genome analysis highlights the extent of genomic variation in cultivated and wild rice. Nat Genet 50, 278–284.Google Scholar
  216. Zhou, J., Lemos, B., Dopman, E.B., and Hartl, D.L. (2011). Copy–number variation: the balance between gene dosage and expression in Drosophila melanogaster. Genome Biol Evol 3, 1014–1024.Google Scholar
  217. Zimin, A.V., Marçais, G., Puiu, D., Roberts, M., Salzberg, S.L., and Yorke, J.A. (2013). The MaSuRCA genome assembler. Bioinformatics 29, 2669–2677.Google Scholar
  218. Zimin, A.V., Puiu, D., Luo, M.C., Zhu, T., Koren, S., Marçais, G., Yorke, J. A., Dvořák, J., and Salzberg, S.L. (2017). Hybrid assembly of the large and highly repetitive genome of Aegilops tauschii, a progenitor of bread wheat, with the MaSuRCA mega–reads algorithm. Genome Res 27, 787–792.Google Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Ecology and Evolutionary BiologyUniversity of CaliforniaIrvineUSA

Personalised recommendations