Journal of Molecular Evolution

, Volume 57, Issue 6, pp 737–744 | Cite as

Lineage-Specific Homogenization of the Polyubiquitin Gene Among Human and Great Apes

  • Hiroshi Tachikui
  • Naruya Saitou
  • Toshiaki Nakajima
  • Ikuo Hayasaka
  • Takafumi Ishida
  • Ituro Inoue


Ubiquitin is a highly conserved protein, and is encoded by a multigene family among eukaryote species. The polyubiquitin genes, UbB and UbC, comprise tandem multiple ubiquitin coding units without a spacer region or intron. We determined nucleotide sequences for the UbB and UbC of human, chimpanzee, gorilla, and orangutan. The ubiquitin repeat number of UbB was constant (3) in human and great apes, while that of UbC varied: 6 to 11 for human, 10 to 12 for chimpanzee, 8 for gorilla, and 10 for orangutan. The heterogeneity of the repeat number within closely related hominoid species suggests that a lineage-specific unequal crossover and/or gene duplication occurred. A marked homogenization of UbC occurred in gorilla with a low level of synonymous difference (p s ). The homogenization of UbC also occurred in chimpanzee and less strikingly in human. The first and last ubiquitin coding units of UbC were clustered independently between species, and less affected by homogenization during the hominoid evolution. Therefore, the homogenization of ubiquitin coding units is likely due to an unequal crossing-over inside the ubiquitin units. The lineage-specific homogenization of UbC among closely related species suggests that concerted evolution has a key role in the short-term evolution of UbC.


Ubiquitin Polyubiquitin gene Concerted evolution Birth-and-death evolution 



This work was supported in part by a Research for the Future Program Grant of The Japan Society for the Promotion of Science to I.I and Grants-in-Aid for Scientific Research on priority areas from the Ministry of Education, Culture, Sport, Science, and Technology of Japan to N.S. We thank Ms. Kozue Otaka for her technical assistance.


  1. 1.
    Altschul, SF, Madden, TL, Schaffer, AA, Zhang, J, Zhang, Z, Miller, W, Lipman, DJ 1997Gapped BLAST and PSI-BLAST: A new generation of protein database search programs.Nucleic Acids Res2533893402PubMedGoogle Scholar
  2. 2.
    Apiou, F, Flagiello, D, Cillo, CB, Malfoy, B, Poupon, MF, Dutrillaux, B 1996Fine mapping of human HOX gene clusters.Cytogenet Cell Genet73114115PubMedGoogle Scholar
  3. 3.
    Bailey, WJ, Kim, J, Wagner, GP, Ruddle, FH 1997Phylogenetic reconstruction of vertebrate Hox cluster duplications.Mol Biol Evol14843853PubMedGoogle Scholar
  4. 4.
    Baker, RT, Board, PG 1987The human ubiquitin gene family: Structure of a gene and pseudogenes from the UbB subfamily.Nucleic Acids Res15443463PubMedGoogle Scholar
  5. 5.
    Baker, RT, Board, PG 1989Unequal crossover generates variation in ubiquitin coding unit number at the human UbC polyubiquitin locus.Am J Hum Genet44534542PubMedGoogle Scholar
  6. 6.
    Baker, RT, Board, PG 1991The human ubiquitin-52 amino acid fusion protein gene shares several structural features with mammalian ribosomal protein genes.Nucleic Acids Res1910351040PubMedGoogle Scholar
  7. 7.
    Board, PG, Coggan, M, Baker, RT, Vuust, J, Webb, GC 1992Localization of the human UBC polyubiquitin gene to chromosome band 12q24.3.Genomics12639642PubMedGoogle Scholar
  8. 8.
    Gonzalez, IL, Sylvester, JE 2001Human rDNA: Evolutionary patterns within the genes and tandem arrays derived from multiple chromosomes.Genomics73255263CrossRefPubMedGoogle Scholar
  9. 9.
    Kasahara, M, Hayashi, M, Tanaka, K, Inoko, H, Sugaya, K, Ikemura, T, Ishibashi, T 1996Chromosomal localization of the proteasome Z subunit gene reveals an ancient chromosomal duplication involving the major histocompatibility complex.Proc Natl Acad Sci USA9390969101CrossRefPubMedGoogle Scholar
  10. 10.
    Kawamura, S, Saitou, N, Ueda, S 1992Concerted evolution of the primate immunoglobulin alpha-gene through gene conversion.J Biol Chem26773597367PubMedGoogle Scholar
  11. 11.
    Keeling, PI, Doolittle, WF 1995Concerted evolution in protists: Recent homogenization of a polyubiquitin gene in Trichomonas vaginalis.J Mol Evol41556562PubMedGoogle Scholar
  12. 12.
    Kimura, M 1980A simple method for estimating evolutionary rate of base substitutions through comparative studies of nucleotide sequences.J Mol Evol16111120PubMedGoogle Scholar
  13. 13.
    Kitano, T, Saitou, N 1999Evolution of the Rh blood group genes has experienced gene conversions and positive selection.J Mol Evol49615626PubMedGoogle Scholar
  14. 14.
    Kumar, S, Tamura, K, Jakobsen, IB, Nei, M 2001MEGA2: Molecular Evolutionary Genetics Analysis software.Bioinformatics1712441245PubMedGoogle Scholar
  15. 15.
    Li, WH 1997Molecular evolution.Sinauer AssociatesSunderland, MAGoogle Scholar
  16. 16.
    Liao, D 1999Concerted evolution: Molecular mechanism and biological implications.Am J Hum Genet642430PubMedGoogle Scholar
  17. 17.
    Lund, PK, Moats-Staats, BM, Simmons, JG, Hoyt, E, D’Ercole, AJ, Martin, F, Van Wyk, JJ 1985Nucleotide sequence analysis of a cDNA encoding human ubiquitin reveals that ubiquitin is synthesized as a precursor.J Biol Chem26076097613PubMedGoogle Scholar
  18. 18.
    Nei, M 1987Molecular evolutionary genetics.Columbia University PressNew YorkGoogle Scholar
  19. 19.
    Nei, M, Rogozin, IB, Piontkivska, H 2000Purifying selection and birth-and-death evolution in the ubiquitin gene family.Proc Natl Acad Sci USA971086610871CrossRefPubMedGoogle Scholar
  20. 20.
    Nenoi, M, Mita, K, Ichimura, S, Cartwright, IL 1994Novel structure of a Chinese hamster polyubiquitin gene.Biochim Biophys Acta1204271278CrossRefPubMedGoogle Scholar
  21. 21.
    Nenoi, M, Mita, K, Ichimura, S, Cartwright, IL, Takahashi, E, Yamauchi, M, Tsuji, H 1996Heterogeneous structure of the polyubiquitin gene UbC of HeLa S3 cells.Gene175179185CrossRefPubMedGoogle Scholar
  22. 22.
    Nenoi, M, Mita, K, Ichimura, S, Kawano, A 1998Higher frequency of concerted evolutionary events in rodents than in man at the polyubiquitin gene VNTR locus.Genetics148867876PubMedGoogle Scholar
  23. 23.
    Nenoi, M, Ichimura, S, Mita, K 2000Interspecific comparison in the frequency of concerted evolution at the polyubiquitin gene locus.J Mol Evol51161165PubMedGoogle Scholar
  24. 24.
    Ohno, S 1970Evolution by gene duplication.Springer-VerlagNew YorkGoogle Scholar
  25. 25.
    Pennisi, E 2001Genome duplications: The stuff of evolution?Science29424582460CrossRefPubMedGoogle Scholar
  26. 26.
    Redman, KL, Rechsteiner, M 1989Identification of the long ubiquitin extension as ribosomal protein S27a.Nature338438440CrossRefPubMedGoogle Scholar
  27. 27.
    Saitou, N, Nei, M 1987The neighbor-joining method: A new method for reconstructing phylogenetic trees.Mol Biol Evol4406425PubMedGoogle Scholar
  28. 28.
    Sharp, PM, Li, WH 1987Ubiquitin genes as a paradigm of concerted evolution of tandem repeats.J Mol Evol255864PubMedGoogle Scholar
  29. 29.
    Skrabanek, L, Wolfe, KH 1998Eukaryote genome duplication—Where’s the evidence?Curr Opin Genet Dev8694700Google Scholar
  30. 30.
    Sidow, A 1996Gen(om)e duplications in the evolution of early vertebrates.Curr Opin Genet Dev6715722PubMedGoogle Scholar
  31. 31.
    Tan, Y, Bishoff, ST, Riley, MA 1993Ubiquitins revisited: Further examples of within- and between-locus concerted evolution.Mol Phylogenet Evol2260351Google Scholar
  32. 32.
    Thompson, JD, Higgins, DG, Gibson, TJ 1994CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice.Nucleic Acids Res2246734680PubMedGoogle Scholar
  33. 33.
    Vrana, PE, Wheeler, WC 1996Molecular evolution and phylogenetic utility of the polyubiquitin locus in mammals and higher vertebrates.Mol Phylogenet Evol6259269PubMedGoogle Scholar
  34. 34.
    Webb, GC, Baker, RT, Fagan, K, Board, PG 1990Localization of the human UbB polyubiquitin gene to chromosome band 17p11.l-17p12.Am J Hum Genet46308315PubMedGoogle Scholar
  35. 35.
    Wiborg, O, Pedersen, MS, Wind, A, Berglund, LE, Marcker, KA, Vuust, J 1985The human ubiquitin multigene family: Some genes contain multiple directly repeated ubiquitin coding sequences.EMBO J4755759PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 2003

Authors and Affiliations

  • Hiroshi Tachikui
    • 1
  • Naruya Saitou
    • 2
  • Toshiaki Nakajima
    • 1
  • Ikuo Hayasaka
    • 3
  • Takafumi Ishida
    • 4
  • Ituro Inoue
    • 1
  1. 1.Division of Genetic Diagnosis, Institute of Medical ScienceUniversity of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639Japan
  2. 2.Division of Population GeneticsNational Institute of Genetics, MishimaJapan
  3. 3.SanwaKagaku Kenkyusho Kumamoto Primate Park, KumamotoJapan
  4. 4.Department of Biological Sciences, Graduate School of ScienceUniversity of Tokyo, TokyoJapan

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