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Global patterns of apparent copy number variation in birds revealed by cross-species comparative genomic hybridization

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Abstract

There is a growing interest in copy number variation (CNV) and the recognition of its importance in phenotype, disease, adaptation and speciation. CNV data is usually ascertained by array-CGH within-species, but similar inter-species comparisons have also been made in primates, mice and domestic mammals. Here, we conducted a broad appraisal of putative cross-species CNVs in birds, 16 species in all, using the standard array-CGH approach. Using a chicken oligonucleotide microarray, we detected 790 apparent CNVs within 135 unique regions and developed a bioinformatic tool ‘CNV Analyser’ for analysing and visualising cross-species data sets. We successfully addressed four hypotheses as follows: (a) Cross-species CNVs (compared to chicken) are, as suggested from preliminary evidence, smaller and fewer in number than in mammals; this ‘dogma’ was rejected in the light of the new evidence. (b) CNVs in birds are likely to have a functional effect through an association with genes; a large proportion of detected regions (70 %) were indeed associated with genes (suggesting functional significance), however, not necessarily more so than in mammals. (c) There are more CNVs in birds with more rearranged karyotypes; this hypothesis was rejected. Indeed, Falco species contained fewer than most with relatively standard (chicken-like) karyotypes. (d) There are more CNVs per megabase on micro-chromosomes than macrochromosomes; this hypothesis was accepted. Indeed, in species with rearranged karyotypes characterised by chromosomal fusions, the fused former microchromosomes still ‘behaved’ as though they were their microchromosomal ancestors. Gene ontology analysis of CNVRs revealed enrichment in immune response and antigen presentation genes and five CNVRs were perfectly correlated with the unique loss of sexual dichromatism in one Galliformes species.

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Abbreviations

CNV:

copy number variation

CNVs:

copy number variants

CNVR:

copy number variable regions

CGH:

comparative genomic hybridization

NAHR:

non allelic homologous recombination

qPCR:

quantitative polymerase chain reaction

FISH:

fluorescence in-situ hybridization

GGA:

Gallus gallus (chicken)

MHC:

major histocompatability complex

References

  • Bailey JA, Eichler EE (2006) Primate segmental duplications: crucibles of evolution, diversity and disease. Nat Rev Genet 7(7):552–564

    Article  PubMed  CAS  Google Scholar 

  • Bed’Hom B, Coullin P, Guillier-Gencik Z, Moulin S, Bernheim A, Volobouev V (2003) Characterization of the atypical karyotype of the black-winged kite Elanus caeruleus (Falconiformes: Accipitridae) by means of classical and molecular cytogenetic techniques. Chromosom Res 11(4):335–343

    Article  Google Scholar 

  • Bonilla AJ, Braun EL, Kimball RT (2010) Comparative molecular evolution and phylogenetic utility of 3′-UTRs and introns in Galliformes. Mol Phylogenet Evol 56(2):536–542

    Article  PubMed  CAS  Google Scholar 

  • Borisov AB, Raeker MO, Kontrogianni-Konstantopoulos A, Yang K, Kurnit DM, Bloch RJ, Russell MW (2003) Rapid response of cardiac obscurin gene cluster to aortic stenosis: differential activation of Rho-GEF and MLCK and involvement in hypertrophic growth. Biochem Biophys Res Commun 310(3):910–918

    Article  PubMed  CAS  Google Scholar 

  • Burt DW (2005) Chicken genome: current status and future opportunities. Genome Res 15(12):1692–1698

    Article  PubMed  CAS  Google Scholar 

  • Burt DW, Bruley C, Dunn IC, Jones CT, Ramage A, Law AS, Morrice DR, Paton IR, Smith J, Windsor D (1999) The dynamics of chromosome evolution in birds and mammals. Nature 402(6760):411–413

    Article  PubMed  CAS  Google Scholar 

  • Chen W-K, Swartz JD, Rush LJ, Alvarez CE (2009) Mapping DNA structural variation in dogs. Genome Res 19(3):500–509

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Colobran R, Pedrosa E, Carretero–Iglesia L, Juan M (2010) Copy number variation in chemokine superfamily: the complex scene of CCL3L–CCL4L genes in health and disease. Clin Exp Immunol 162(1):41–52

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Crooijmans RPMA, Fife MS, Fitzgerald T, Strickland S, Cheng HH, Kaiser P, Redon R, Groenen MAM (2013) Large scale variation in DNA copy number in chicken breeds. BMC Genomics 14:398

    Article  PubMed Central  PubMed  Google Scholar 

  • Da Wei Huang BTS, Lempicki RA (2008) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57

    Article  CAS  Google Scholar 

  • Dalloul RA, Long JA, Zimin AV, Aslam L, Beal K, Bouffard P, Burt DW, Crasta O, Crooijmans RP, Cooper K (2010) Multi-platform next-generation sequencing of the domestic turkey (Meleagris gallopavo): genome assembly and analysis. PLoS Biol 8(9):e1000475

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Dumas L, Kim YH, Karimpour-Fard A, Cox M, Hopkins J, Pollack JR, Sikela JM (2007) Gene copy number variation spanning 60 million years of human and primate evolution. Genome Res 17(9):1266–1277

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Emanuel BS, Saitta SC (2007) From microscopes to microarrays: dissecting recurrent chromosomal rearrangements. Nat Rev Genet 8(11):869–883

    Article  PubMed Central  PubMed  Google Scholar 

  • Ewald S, Livant E (2004) Distinctive polymorphism of chicken B-FI (major histocompatibility complex class I) molecules. Poult Sci 83(4):600–605

    Article  PubMed  CAS  Google Scholar 

  • Fadista J, Nygaard M, Holm L-E, Thomsen B, Bendixen C (2008) A snapshot of CNVs in the pig genome. PLoS One 3(12):e3916

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Fadista J, Thomsen B, Holm L-E, Bendixen C (2010) Copy number variation in the bovine genome. BMC Genomics 11(1):284

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Feuk L, Carson AR, Scherer SW (2006) Structural variation in the human genome. Nat Rev Genet 7(2):85–97

    Article  PubMed  CAS  Google Scholar 

  • Fontanesi L, Martelli P, Beretti F, Riggio V, Dall’Olio S, Colombo M, Casadio R, Russo V, Portolano B (2010) An initial comparative map of copy number variations in the goat (Capra hircus) genome. BMC Genomics 11(1):639

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Fontanesi L, Beretti F, Martelli P, Colombo M, Dall’Olio S, Occidente M, Portolano B, Casadio R, Matassino D, Russo V (2011) A first comparative map of copy number variations in the sheep genome. Genomics 97(3):158–165

    Article  PubMed  CAS  Google Scholar 

  • Fortna A, Kim Y, MacLaren E, Marshall K, Hahn G, Meltesen L, Brenton M, Hink R, Burgers S, Hernandez-Boussard T (2004) Lineage-specific gene duplication and loss in human and great ape evolution. PLoS Biology 2(7):e207

    Article  PubMed Central  PubMed  Google Scholar 

  • Freeman JL, Perry GH, Feuk L, Redon R, McCarroll SA, Altshuler DM, Aburatani H, Jones KW, Tyler-Smith C, Hurles ME (2006) Copy number variation: new insights in genome diversity. Genome Res 16(8):949–961

    Article  PubMed  CAS  Google Scholar 

  • Frey N, Olson EN (2002) Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin family, interacts with multiple Z-disc proteins. J Biol Chem 277(16):13998–14004

    Article  PubMed  CAS  Google Scholar 

  • Graubert TA, Cahan P, Edwin D, Selzer RR, Richmond TA, Eis PS, Shannon WD, Li X, McLeod HL, Cheverud JM (2007) A high-resolution map of segmental DNA copy number variation in the mouse genome. PLoS Genet 3(1):e3

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gregory TR (2005) The evolution of the genome. Academic Press

  • Griffin D, Robertson L, Tempest H, Skinner B (2007) The evolution of the avian genome as revealed by comparative molecular cytogenetics. Cytogenetic Genome Res 117(1–4):64–77

    Article  CAS  Google Scholar 

  • Griffin DK, Robertson LB, Tempest HG, Vignal A, Fillon V, Crooijmans RP, Groenen MA, Deryusheva S, Gaginskaya E, Carré W (2008) Whole genome comparative studies between chicken and turkey and their implications for avian genome evolution. BMC genomics 9(1):168

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hillier LW, Miller W, Birney E, Warren W, Hardison RC, Ponting CP, Bork P, Burt DW, Groenen MA, Delany ME (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432(7018):695–716

    Article  CAS  Google Scholar 

  • Iskow RC, Gokcumen O, Lee C (2012) Exploring the role of copy number variants in human adaptation. Trends in Genetics

  • Jurata LW, Gill GN (1997) Functional analysis of the nuclear LIM domain interactor NLI. Mol Cell Biol 17(10):5688–5698

    PubMed Central  PubMed  CAS  Google Scholar 

  • Kehrer-Sawatzki H, Cooper DN (2008) Molecular mechanisms of chromosomal rearrangement during primate evolution. Chromosom Res 16(1):41–56

    Article  CAS  Google Scholar 

  • Kimball RT, Braun EL (2008) A multigene phylogeny of Galliformes supports a single origin of erectile ability in non–feathered facial traits. J Avian Biol 39(4):438–445

    Google Scholar 

  • Kimball RT, Mary CMS, Braun EL (2011) A macroevolutionary perspective on multiple sexual traits in the Phasianidae (Galliformes). International, journal of evolutionary biology 2011

  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921

    Article  PubMed  CAS  Google Scholar 

  • Lee CW, Hwang I, Park C-S, Lee H, Park D-W, Kang S-J, Lee S-W, Kim Y-H, Park S-W, Park S-J (2012) Expression of ADAMTS-2,-3,-13, and-14 in culprit coronary lesions in patients with acute myocardial infarction or stable angina. J Thromb Thrombolysis 33(4):362–370

    Article  PubMed  CAS  Google Scholar 

  • Liu GE, Hou Y, Zhu B, Cardone MF, Jiang L, Cellamare A, Mitra A, Alexander LJ, Coutinho LL, Dell’Aquila ME (2010) Analysis of copy number variations among diverse cattle breeds. Genome Res 20(5):693–703

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Locke DP, Segraves R, Carbone L, Archidiacono N, Albertson DG, Pinkel D, Eichler EE (2003) Large-scale variation among human and great ape genomes determined by array comparative genomic hybridization. Genome Res 13(3):347–357

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lupski JR (1998) Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet: TIG 14(10):417

    Article  PubMed  CAS  Google Scholar 

  • Mah W, Ko J, Nam J, Han K, Chung WS, Kim E (2010) Selected SALM (synaptic adhesion-like molecule) family proteins regulate synapse formation. J Neurosci 30(16):5559–5568

    Article  PubMed  CAS  Google Scholar 

  • Nanda I, Karl E, Volobouev V, Griffin D, Schartl M, Schmid M (2006) Extensive gross genomic rearrangements between chicken and Old World vultures (Falconiformes: Accipitridae). Cytogenetic Genome Res 112(3–4):286–295

    Article  CAS  Google Scholar 

  • Newman TL, Tuzun E, Morrison VA, Hayden KE, Ventura M, McGrath SD, Rocchi M, Eichler EE (2005) A genome-wide survey of structural variation between human and chimpanzee. Genome Res 15(10):1344–1356

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nishida C, Ishijima J, Kosaka A, Tanabe H, Habermann FA, Griffin DK, Matsuda Y (2008) Characterization of chromosome structures of Falconinae (Falconidae, Falconiformes, Aves) by chromosome painting and delineation of chromosome rearrangements during their differentiation. Chromosom Res 16(1):171–181

    Article  CAS  Google Scholar 

  • Ohno S (1970) Evolution by gene duplication. London: George Alien & Unwin Ltd. Berlin, Heidelberg and New York: Springer-Verlag

  • Olshen AB, Venkatraman E, Lucito R, Wigler M (2004) Circular binary segmentation for the analysis of array–based DNA copy number data. Biostatistics 5(4):557–572

    Article  PubMed  Google Scholar 

  • Perry GH, Tchinda J, McGrath SD, Zhang J, Picker SR, Cáceres AM, Iafrate AJ, Tyler-Smith C, Scherer SW, Eichler EE (2006) Hotspots for copy number variation in chimpanzees and humans. Proc Natl Acad Sci 103(21):8006–8011

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Perry GH, Dominy NJ, Claw KG, Lee AS, Fiegler H, Redon R, Werner J, Villanea FA, Mountain JL, Misra R (2007) Diet and the evolution of human amylase gene copy number variation. Nature genetics 39(10):1256–1260

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, Fiegler H, Shapero MH, Carson AR, Chen W (2006) Global variation in copy number in the human genome. Nature 444(7118):444–454

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Repping S, van Daalen SK, Brown LG, Korver CM, Lange J, Marszalek JD, Pyntikova T, van der Veen F, Skaletsky H, Page DC (2006) High mutation rates have driven extensive structural polymorphism among human Y chromosomes. Nat Genet 38(4):463–467

    Article  PubMed  CAS  Google Scholar 

  • Samonte RV, Eichler EE (2002) Segmental duplications and the evolution of the primate genome. Nat Rev Genet 3(1):65–72

    Article  PubMed  CAS  Google Scholar 

  • Schmid M, Nanda I, Burt DW (2005) Second report on chicken genes and chromosomes 2005. Cytogenetic and Genome Res 109(4):415–479

    Article  CAS  Google Scholar 

  • Skinner B, Griffin D (2011) Intrachromosomal rearrangements in avian genome evolution: evidence for regions prone to breakpoints. Heredity 108(1):37–41

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Skinner B, Robertson L, Tempest H, Langley E, Ioannou D, Fowler K, Crooijmans R, Hall A, Griffin D, Völker M (2009) Comparative genomics in chicken and Pekin duck using FISH mapping and microarray analysis. BMC genomics 10(1):357

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • St Clair D (2009) Copy number variation and schizophrenia. Schizophr Bull 35(1):9–12

    Article  PubMed Central  PubMed  Google Scholar 

  • Stankiewicz P, Lupski JR (2002) Genome architecture, rearrangements and genomic disorders. Trends Genet: TIG 18(2):74

    Article  PubMed  CAS  Google Scholar 

  • Stefansson H, Rujescu D, Cichon S, Pietiläinen OP, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE (2008) Large recurrent microdeletions associated with schizophrenia. Nature 455(7210):232–236

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Szmola R, Kukor Z, Sahin-Tóth M (2003) Human mesotrypsin is a unique digestive protease specialized for the degradation of trypsin inhibitors. J Biol Chem 278(49):48580–48589

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Völker M, Backström N, Skinner BM, Langley EJ, Bunzey SK, Ellegren H, Griffin DK (2010) Copy number variation, chromosome rearrangement, and their association with recombination during avian evolution. Genome Res 20(4):503–511

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wang X, Nahashon S, Feaster TK, Bohannon-Stewart A, Adefope N (2010) An initial map of chromosomal segmental copy number variations in the chicken. BMC Genomics 11(1):351

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wang J, Jiang J, Fu W, Jiang L, Ding X, Liu J-F, Zhang Q (2012) A genome-wide detection of copy number variations using SNP genotyping arrays in swine. BMC Genomics 13(1):273

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Warren WC, Clayton DF, Ellegren H, Arnold AP, Hillier LW, Künstner A, Searle S, White S, Vilella AJ, Fairley S (2010) The genome of a songbird. Nature 464(7289):757–762

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Watson KL, Justice RW, Bryant PJ (1994) Drosophila in cancer research: the first fifty tumor suppressor genes. J Cell Sci Suppl 18:19

    Article  PubMed  CAS  Google Scholar 

  • Workman C, Jensen LJ, Jarmer H, Berka R, Gautier L, Nielser HB, Saxild H-H, Nielsen C, Brunak S, Knudsen S (2002) A new non-linear normalization method for reducing variability in DNA microarray experiments. Genome Biol 3(9):1–16

    Article  Google Scholar 

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Acknowledgements

We thank Wingham Wildlife Park, Kent, Cherry Valley Farms, British United Turkeys, and the Central Veterinary Research Laboratory in Dubai, and the Falcon Hospital Dubai for providing feathers and blood samples from which the DNA samples were extracted.

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Authors and Affiliations

  1. School of Biosciences, University of Kent, Canterbury, UK, CT2 7NJ

    Benjamin M. Skinner, Abdullah Al Mutery, Deborah Smith, Martin Völker, Nilofour Hojjat, Sannaa Raja, Steven Trim & Darren K. Griffin

  2. Department of Pathology, University of Cambridge, Cambridge, UK, CB2 1QP

    Benjamin M. Skinner

  3. Department of Applied Biology, University of Sharjah, Sharjah, United Arab Emirates

    Abdullah Al Mutery

  4. Department of Biology, New Mexico State University, Las Cruces, NM, 88003, USA

    Peter Houde & William J. Boecklen

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  1. Benjamin M. Skinner
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  2. Abdullah Al Mutery
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  3. Deborah Smith
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  4. Martin Völker
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  5. Nilofour Hojjat
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  6. Sannaa Raja
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  7. Steven Trim
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  10. Darren K. Griffin
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Correspondence to Darren K. Griffin.

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Responsible Editors: Darren K. Griffin and Beth A. Sullivan.

Benjamin M. Skinner, Abdullah Al Mutery, and Deborah Smith are joint first authors for this article.

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ESM 1

(XLS 311 kb)

ESM 2

Numbers of CNVRs containing genes in each species, and the proportion of genes that are protein-coding (EPS 2389 kb)

High Resolution Image (JPEG 849 kb)

ESM 3

Heatmap in which gains are shown in green, losses in red, with the brightness proportional to the log2 ratio of the CNV. The animals and CNVs have been clustered, revealing patterns of lineage-specific CNVRs, and demonstrating that losses are more frequently shared across multiple species than gains (EPS 5090 kb)

High Resolution Image (JPEG 1428 kb)

ESM 4

The number of CNVRs which are unique to one species, or which are shared between two or more species. Gains are shared between at most four species; losses are shared with up to 18 species. Shared losses are likely attributable to sequence divergence rather than true copy number change (EPS 1300 kb)

High Resolution Image (JPEG 341 kb)

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Skinner, B.M., Al Mutery, A., Smith, D. et al. Global patterns of apparent copy number variation in birds revealed by cross-species comparative genomic hybridization. Chromosome Res 22, 59–70 (2014). https://doi.org/10.1007/s10577-014-9405-0

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