BACKGROUND: Retrotransposons have been suggested to provide a substrate for non-allelic homologous recombination (NAHR) and thereby promote gene family expansion. Their precise role, however, is controversial. Here we ask whether retrotransposons contributed to the recent expansions of the Androgen-binding protein (Abp) gene families that occurred independently in the mouse and rat genomes. RESULTS: Using dot plot analysis, we found that the most recent duplication in the Abp region of the mouse genome is flanked by L1Md_T elements. Analysis of the sequence of these elements revealed breakpoints that are the relicts of the recombination that caused the duplication, confirming that the duplication arose as a result of NAHR using L1 elements as substrates. L1 and ERVII retrotransposons are considerably denser in the Abp regions than in one Mb flanking regions, while other repeat types are depleted in the Abp regions compared to flanking regions. L1 retrotransposons preferentially accumulated in the Abp gene regions after lineage separation and roughly followed the pattern of Abp gene expansion. By contrast, the proportion of shared vs. lineage-specific ERVII repeats in the Abp region resembles the rest of the genome. CONCLUSIONS: We confirmed the role of L1 repeats in Abp gene duplication with the identification of recombinant L1Md_T elements at the edges of the most recent mouse Abp gene duplication. High densities of L1 and ERVII repeats were found in the Abp gene region with abrupt transitions at the region boundaries, suggesting that their higher densities are tightly associated with Abp gene duplication. We observed that the major accumulation of L1 elements occurred after the split of the mouse and rat lineages and that there is a striking overlap between the timing of L1 accumulation and expansion of the Abp gene family in the mouse genome. Establishing a link between the accumulation of L1 elements and the expansion of the Abp gene family and identification of an NAHR-related breakpoint in the most recent duplication are the main contributions of our study.

Department of Zoology Faculty of Science Charles University Prague Prague 128 43 Czech Republic

Zobrazit více v PubMed

Ohno S. Sex chromosomes and sex-linked genes. Berlin, New York: Springer-Verlag; 1967.

Ohno S. Evolution by gene duplication. New York: Springer Verlag; 1970.

Ponting CP. The functional repertoires of metazoan genomes. Nat Rev Genet. 2008;9(9):689–698. doi: 10.1038/nrg2413. PubMed DOI

Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004;428(6982):493–521. PubMed

Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921. doi: 10.1038/35057062. PubMed DOI

Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P. Initial sequencing and comparative analysis of the mouse genome. Nature. 2002;420(6915):520–562. doi: 10.1038/nature01262. PubMed DOI

Hurst LD, Smith NG. Do essential genes evolve slowly? Curr Biol. 1999;9(14):747–750. doi: 10.1016/S0960-9822(99)80334-0. PubMed DOI

Birtle Z, Goodstadt L, Ponting C. Duplication and positive selection among hominin-specific PRAME genes. BMC Genomics. 2005;6:120. doi: 10.1186/1471-2164-6-120. PubMed DOI PMC

Emes RD, Riley MC, Laukaitis CM, Goodstadt L, Karn RC, Ponting CP. Comparative evolutionary genomics of androgen-binding protein genes. Genome Res. 2004;14(8):1516–1529. doi: 10.1101/gr.2540304. PubMed DOI PMC

Goldstone HM, Stegeman JJ. A revised evolutionary history of the CYP1A subfamily: gene duplication, gene conversion, and positive selection. J Mol Evol. 2006;62(6):708–717. doi: 10.1007/s00239-005-0134-z. PubMed DOI

Johnston CR, O’Dushlaine C, Fitzpatrick DA, Edwards RJ, Shields DC. Evaluation of whether accelerated protein evolution in chordates has occurred before, after, or simultaneously with gene duplication. Mol Biol Evol. 2007;24(1):315–323. PubMed

Nielsen R, Bustamante C, Clark AG, Glanowski S, Sackton TB, Hubisz MJ, Fledel-Alon A, Tanenbaum DM, Civello D, White TJ. A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol. 2005;3(6):e170. doi: 10.1371/journal.pbio.0030170. PubMed DOI PMC

Ponting CP, Goodstadt L. Separating derived from ancestral features of mouse and human genomes. Biochem Soc Trans. 2009;37(Pt 4):734–739. PubMed

Ostertag EM, Kazazian HH Jr. Biology of mammalian L1 retrotransposons. Annu Rev Genet. 2001;35:501–538. doi: 10.1146/annurev.genet.35.102401.091032. PubMed DOI

Babcock M, Pavlicek A, Spiteri E, Kashork CD, Ioshikhes I, Shaffer LG, Jurka J, Morrow BE. Shuffling of genes within low-copy repeats on 22q11 (LCR22) by Alu-mediated recombination events during evolution. Genome Res. 2003;13(12):2519–2532. doi: 10.1101/gr.1549503. PubMed DOI PMC

Bailey JA, Church DM, Ventura M, Rocchi M, Eichler EE. Analysis of segmental duplications and genome assembly in the mouse. Genome Res. 2004;14(5):789–801. doi: 10.1101/gr.2238404. PubMed DOI PMC

Bailey JA, Liu G, Eichler EE. An Alu transposition model for the origin and expansion of human segmental duplications. Am J Hum Genet. 2003;73(4):823–834. doi: 10.1086/378594. PubMed DOI PMC

Tuzun E, Bailey JA, Eichler EE. Recent segmental duplications in the working draft assembly of the brown Norway rat. Genome Res. 2004;14(4):493–506. doi: 10.1101/gr.1907504. PubMed DOI PMC

Giannuzzi G, D’Addabbo P, Gasparro M, Martinelli M, Carelli FN, Antonacci D, Ventura M. Analysis of high-identity segmental duplications in the grapevine genome. BMC Genomics. 2011;12:436. doi: 10.1186/1471-2164-12-436. PubMed DOI PMC

Liu Y, Qin X, Song XZ, Jiang H, Shen Y, Durbin KJ, Lien S, Kent MP, Sodeland M, Ren Y. Bos taurus genome assembly. BMC Genomics. 2009;10:180. doi: 10.1186/1471-2164-10-180. PubMed DOI PMC

She X, Cheng Z, Zollner S, Church DM, Eichler EE. Mouse segmental duplication and copy number variation. Nat Genet. 2008;40(7):909–914. doi: 10.1038/ng.172. PubMed DOI PMC

Zhou Y, Mishra B. Quantifying the mechanisms for segmental duplications in mammalian genomes by statistical analysis and modeling. Proc Natl Acad Sci U S A. 2005;102(11):4051–4056. doi: 10.1073/pnas.0407957102. PubMed DOI PMC

Fitch DH, Bailey WJ, Tagle DA, Goodman M, Sieu L, Slightom JL. Duplication of the gamma-globin gene mediated by L1 long interspersed repetitive elements in an early ancestor of simian primates. Proc Natl Acad Sci U S A. 1991;88(16):7396–7400. doi: 10.1073/pnas.88.16.7396. PubMed DOI PMC

Guo X, Freyer L, Morrow B, Zheng D. Characterization of the past and current duplication activities in the human 22q11.2 region. BMC Genomics. 2011;12:71. doi: 10.1186/1471-2164-12-71. PubMed DOI PMC

Hahn MW, Demuth JP, Han SG. Accelerated rate of gene gain and loss in primates. Genetics. 2007;177(3):1941–1949. doi: 10.1534/genetics.107.080077. PubMed DOI PMC

Murakami H, Aburatani S, Horimoto K. Relationship between segmental duplications and repeat sequences in human chromosome 7. Genome informatics International Conference on Genome Informatics. 2005;16(1):13–21. PubMed

Glusman G, Clifton S, Roe B, Lancet D. Sequence analysis in the olfactory receptor gene cluster on human chromosome 17: recombinatorial events affecting receptor diversity. Genomics. 1996;37(2):147–160. doi: 10.1006/geno.1996.0536. PubMed DOI

Kambere MB, Lane RP. Exceptional LINE density at V1R loci: the Lyon repeat hypothesis revisited on autosomes. J Mol Evol. 2009;68(2):145–159. doi: 10.1007/s00239-008-9195-0. PubMed DOI

Arnheim N. In: Evolution of Genes and Proteins. Nei M, RK K, editor. Sunderland: Sinauer; 1983. Concerted evolution of multigene families; pp. 38–61.

Hurst GD, Werren JH. The role of selfish genetic elements in eukaryotic evolution. Nat Rev Genet. 2001;2(8):597–606. doi: 10.1038/35084545. PubMed DOI

Witherspoon DJ, Watkins WS, Zhang Y, Xing J, Tolpinrud WL, Hedges DJ, Batzer MA, Jorde LB. Alu repeats increase local recombination rates. BMC Genomics. 2009;10:530. doi: 10.1186/1471-2164-10-530. PubMed DOI PMC

Yang S, Arguello JR, Li X, Ding Y, Zhou Q, Chen Y, Zhang Y, Zhao R, Brunet F, Peng L. Repetitive element-mediated recombination as a mechanism for new gene origination in Drosophila. PLoS Genet. 2008;4(1):e3. doi: 10.1371/journal.pgen.0040003. PubMed DOI PMC

Arnheim N, Calabrese P, Tiemann-Boege I. Mammalian meiotic recombination hot spots. Annu Rev Genet. 2007;41:369–399. doi: 10.1146/annurev.genet.41.110306.130301. PubMed DOI

Jurka J, Kohany O, Pavlicek A, Kapitonov VV, Jurka MV. Clustering, duplication and chromosomal distribution of mouse SINE retrotransposons. Cytogenet Genome Res. 2005;110(1–4):117–123. PubMed

Paigen K, Szatkiewicz JP, Sawyer K, Leahy N, Parvanov ED, Ng SH, Graber JH, Broman KW, Petkov PM. The recombinational anatomy of a mouse chromosome. PLoS Genet. 2008;4(7):e1000119. doi: 10.1371/journal.pgen.1000119. PubMed DOI PMC

Shifman S, Bell JT, Copley RR, Taylor MS, Williams RW, Mott R, Flint J. A high-resolution single nucleotide polymorphism genetic map of the mouse genome. PLoS Biol. 2006;4(12):e395. doi: 10.1371/journal.pbio.0040395. PubMed DOI PMC

Smagulova F, Gregoretti IV, Brick K, Khil P, Camerini-Otero RD, Petukhova GV. Genome-wide analysis reveals novel molecular features of mouse recombination hotspots. Nature. 2011;472(7343):375–378. doi: 10.1038/nature09869. PubMed DOI PMC

Song M, Boissinot S. Selection against LINE-1 retrotransposons results principally from their ability to mediate ectopic recombination. Gene. 2007;390(1–2):206–213. PubMed

Paigen K, Petkov P. Mammalian recombination hot spots: properties, control and evolution. Nat Rev Genet. 2010;11(3):221–233. doi: 10.1038/nrg2712. PubMed DOI PMC

Laukaitis CM, Heger A, Blakley TD, Munclinger P, Ponting CP, Karn RC. Rapid bursts of androgen-binding protein (Abp) gene duplication occurred independently in diverse mammals. BMC Evol Biol. 2008;8:46. doi: 10.1186/1471-2148-8-46. PubMed DOI PMC

Karn RC, Laukaitis CM. The mechanism of expansion and the volatility it created in three pheromone gene clusters in the mouse (Mus musculus) genome. Genome Biol Evol. 2009;1:494–503. PubMed PMC

Laukaitis CM, Critser ES, Karn RC. Salivary androgen-binding protein (ABP) mediates sexual isolation in Mus musculus. Evolution. 1997;51(6):2000–2005. doi: 10.2307/2411020. PubMed DOI

Talley HM, Laukaitis CM, Karn RC. Female preference for male saliva: implications for sexual isolation of Mus musculus subspecies. Evolution. 2001;55(3):631–634. doi: 10.1554/0014-3820(2001)055[0631:FPFMSI]2.0.CO;2. PubMed DOI

Laukaitis C, Karn RC. In: Evolution of the House Mouse. Macholan M, Munclinger P, Baird SJ, Pialek JWN, editor. NY: Cambridge University Press; 2012. Recognition of subspecies status mediated by androgen-binding protein (ABP) in the evolution of incipient reinforcement on the European house mouse hybrid zone; pp. 150–190.

Vošlajerová Bímová B, Macholán M, Baird SEB, Munclinger P, Laukaitis CM, Karn RC, Luzynski K, Tucker P, Piálek J. Reinforcement selection acting on the European house mouse hybrid zone. Mol Ecol. 2011;20:2403–2424. doi: 10.1111/j.1365-294X.2011.05106.x. PubMed DOI

Karolchik D, Baertsch R, Diekhans M, Furey TS, Hinrichs A, Lu YT, Roskin KM, Schwartz M, Sugnet CW, Thomas DJ. The UCSC Genome Browser Database. Nucleic Acids Res. 2003;31(1):51–54. doi: 10.1093/nar/gkg129. PubMed DOI PMC

Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W. Human-mouse alignments with BLASTZ. Genome Res. 2003;13(1):103–107. doi: 10.1101/gr.809403. PubMed DOI PMC

R Development Core Team. R: A Language and Environment for Statistical Computing, Reference Index Version 2.13.1. Vienna, Austria: R Foundation for Statistical Computing; 2011.

Smit AFA, Hubley R, Green P. RepeatMasker Open-3.0. 1996-2010. http://www.repeatmasker.org/

Edgar RC. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinforma. 2004;5:113. doi: 10.1186/1471-2105-5-113. PubMed DOI PMC

Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004;32(5):1792–1797. doi: 10.1093/nar/gkh340. PubMed DOI PMC

Paradis E, Claude J, Strimmer K. APE: Analyses of Phylogenetics and Evolution in R language. Bioinformatics. 2004;20(2):289–290. doi: 10.1093/bioinformatics/btg412. PubMed DOI

Katju V, Lynch M. The structure and early evolution of recently arisen gene duplicates in the Caenorhabditis elegans genome. Genetics. 2003;165(4):1793–1803. PubMed PMC

Expansion of the fatty acyl reductase gene family shaped pheromone communication in Hymenoptera

Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes

The Role of Retrotransposons in Gene Family Expansions in the Human and Mouse Genomes