Journal of Molecular Evolution

, Volume 33, Issue 1, pp 34–41 | Cite as

Multigene families and the evolution of complexity

  • Tomoko Ohta


Higher organisms are complex, and their developmental processes are controlled by the sequential expression of genes that often form multigene families. Facts are surveyed on how functional diversity of genes is related to duplication of genes or segments of genes, by emphasizing that diversity is often enhanced by alternate splicing and proteolytic cleavage involving duplicated genes or gene segments. Analyses of a population genetics model for the origin of gene families suggest that positive Darwinian selection is needed for acquiring gene families with desirable functions. Based on these considerations, examples that show acceleration of amino acid substitution relative to synonymous change during evolutionary processes are surveyed. Some of such examples strongly suggest that positive selection has worked. In other cases it is difficult to judge whether or not acceleration is caused by positive Darwinian selection. As a general pattern, acceleration of amino acid substitution is often found to be related to gene duplication. It is thought that complexity and diversity of gene function have been advantageous in the long evolutionary course of higher organisms.

Key words

Gene duplication Progressive evolution Acceleration of amino acid substitutions 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987a) Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329:506–512CrossRefPubMedGoogle Scholar
  2. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987b) The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329:512–518CrossRefPubMedGoogle Scholar
  3. Bodmer WF (1981) The William Allan Memorial Award address: Gene clusters, genome organization, and complex phenotypes. When the sequence is known, what will it mean? Am J Hum Genet 33:664–682PubMedGoogle Scholar
  4. Bothwell ALM, Paskind M, Reth M, Imanishi-Kari T, Rajewsky K, Baltimore D (1981) Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a γ2a variable region. Cell 24:625–637CrossRefPubMedGoogle Scholar
  5. Breitbart RE, Andreadis A, Nadal-Ginard B (1987) Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from signel genes. Annu Rev Biochem 56:467–495CrossRefPubMedGoogle Scholar
  6. Britten RJ (1986) Rates of DNA sequence evolution differ between taxonomic groups. Science 231:1393–1398PubMedGoogle Scholar
  7. Creighton TE, Darby NJ (1989) Functional evolutionary divergence of proteolytic enzymes and their inhibitors. Trends Biochem Sci 14:319–324CrossRefPubMedGoogle Scholar
  8. de Jong WW, Hendriks W, Mulders JWM, Bloemendal H (1989) Evolution of eye lens crystallins: the stress connection. Trends Biochem Sci 14:365–368CrossRefPubMedGoogle Scholar
  9. Ebina Y, Ellis L, Jarnagin K, Edery M, Graf L, Clauser E, Ou J-H, Masiarz F, Kan YW, Goldfine ID, Roth RA, Rutter WJ (1985) The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. Cell 40:747–758CrossRefPubMedGoogle Scholar
  10. Gillespie JH (1986) Variability of evolutionary rates of DNA. Genetics 113:1077–1091PubMedGoogle Scholar
  11. Goldsmith MR, Kafatos FC (1984) Developmentally regulated genes in silkmoths. Annu Rev Genet 18:443–487CrossRefPubMedGoogle Scholar
  12. Goodman M (1976) Protein sequences in phylogeny. In: Ayala FJ (ed) Molecular evolution. Sinauer Associates, Sunderland, MA, pp 141–159Google Scholar
  13. Goodman M, Czelusniak J, Koop BF, Tagle DA, Slightom JL (1987) Globins: a case study in molecular phylogeny. Proc Cold Spring Harbor Symp Quant Biol 52:875–890Google Scholar
  14. Hoffman S, Edelman GM (1983) Kinetics of homophilic binding by embryonic and adult forms of the neural cell adhesion molecule. Proc Natl Acad Sci USA 80:5762–5766PubMedGoogle Scholar
  15. Hughes AL, Nei M (1988) Pattern of nucleotide substitution at major histocompatibility complex loci reveals overdominant selection. Nature 335:167–170CrossRefPubMedGoogle Scholar
  16. Hughes AL, Nei M (1989) Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection. Proc Natl Acad Sci USA 86:958–962PubMedGoogle Scholar
  17. Hunter T (1987) A thousand and one protein kinases. Cell 50:823–829CrossRefPubMedGoogle Scholar
  18. Jollès J, Pollès P, Bowman BH, Prager EM, Stewart C-B, Wilson AC (1989) Episodic evolution in the stomach lysozymes of ruminants. J Mol Evol 28:528–535PubMedGoogle Scholar
  19. Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, LondonGoogle Scholar
  20. Kimura M, Ohta T (1971) Theoretical aspects of population genetics. Princeton University Press, PrincetonGoogle Scholar
  21. Klein J, Figueroa F (1986) Evolution of the major histocompatibility complex. CRC Crit Rev Immunol 6:295–386Google Scholar
  22. Lalanne JL, Bregegere F, Delarbre C, Abastado JP, Gachelin G, Kourilsky P (1982) Comparison of nucleotide sequences of mRNAs belonging to the mouse H-2 multigene family. Nucleic Acids Res 10:1039–1049PubMedGoogle Scholar
  23. Li W-H (1985) Accelerated evolution following gene duplication and its implication for the neutralist-selectionist controversy. In: Ohta T, Aoki K (eds) Population genetics and molecular evolution. Springer, Berlin, pp 333–352Google Scholar
  24. Li W-H, Gojobori T (1983) Rapid evolution of goat and sheep globin genes following gene duplication. Mol Biol Evol 1:94–108PubMedGoogle Scholar
  25. Markert CL (1987) Isozymes and the regulatory structure of the genome. In: Markert CL (ed) Current topics in biological and medical research, vol 14. Molecular and cellular biology, Alan R. Liss. New York, pp 1–17Google Scholar
  26. Noda M, Furutani Y, Takahashi H, Toyosato M, Hirose T, Inayama S, Nakanishi S, Numa S (1982) Cloning and sequencing analysis of cDNA for bovine adrenal preproenkephalin. Nature 295:202–206CrossRefPubMedGoogle Scholar
  27. O'Brien SJ, Goldman D, Merril CR, Bush M (1983) The cheetah is depauperate in genetic variation. Science 221:459–462Google Scholar
  28. Ohta T (1980) Evolution and variation of multigene families. Lecture notes in biomathematics, vol 37. Springer-Verlag, BerlinGoogle Scholar
  29. Ohta T (1983) On the evolution of multigene families. Theor Pop Biol 23:216–240CrossRefGoogle Scholar
  30. Ohta T (1987) Simulating evolution by gene duplication. Genetics 115:207–213PubMedGoogle Scholar
  31. Ohta T (1988a) Further simulation studies on evolution by gene duplication. Evolution 42:375–386Google Scholar
  32. Ohta T (1988b) Time for acquiring a new gene by duplication. Proc Natl Acad Sci USA 85:3509–3512PubMedGoogle Scholar
  33. Ohta T (1988c) Multigene and supergene families. In: Harvey PH, Partridge L (eds) Oxford surveys in evolutionary biology, vol 5. Oxford University Press, Oxford, pp 41–65Google Scholar
  34. Ohta T (1991) Evolution of multigene family — a case of dynamically evolving genes at major histocompatibility complex. In: Osawa S, Honjo T (eds) Evolution of life. Springer, Berlin (in press)Google Scholar
  35. Perutz MF (1983) Species adaptation in a protein molecule. Mol Biol Evol 1:1–28PubMedGoogle Scholar
  36. Rasmussen N (1987) A new model of developmental constraints as applied to theDrosophila system. J Theor Biol 127:271–299PubMedGoogle Scholar
  37. Savage DE, Russell DE (1983) Mammalian paleofaunas of the world. Addison-Wesley, Reading MAGoogle Scholar
  38. Scheller RH, Jackson JF, McAllister LB, Schwartz JH, Kandel ER, Axel R (1982) A family of genes that codes for ELH, a neuropeptide eliciting a stereotyped pattern of behavior inAplysia. Cell 28:707–719CrossRefPubMedGoogle Scholar
  39. Sheppard HW, Gutman GA (1981) Allelic forms of rat κ chain genes: evidence for strong selection at the level of nucleotide sequence. Proc Natl Acad Sci USA 78:7064–7068PubMedGoogle Scholar
  40. Stewart C-B, Schilling JW, Wilson AC (1987) Adaptive evolution in the stomach lysozymes of foregut fermenters. Nature 330:401–404CrossRefPubMedGoogle Scholar
  41. Streilein JW, Duncan WR (1983) On the anomalous nature of the major histocompatibility complex in Syrian hamsters, Hm-1. Trans Proc 15:1540–1545Google Scholar
  42. Walsh JB (1987) Sequence-dependent gene conversion: can duplicated genes diverge fast enough to escape conversion? Genetics 117:543–557PubMedGoogle Scholar
  43. Wistow GJ, Mulders JWM, de Jong WW (1987) The enzyme lactate dehydrogenase as a structural protein in avian and crocodilian lenses. Nature 326:622–624CrossRefPubMedGoogle Scholar
  44. Yokoyama S, Yokoyama R (1990) Molecular evolution of visual pigment genes and other G-protein-coupled receptor genes. In: Takahata N, Crow JF (eds) Population biology of genes and molecules. Baifukan, Tokyo, pp 307–322Google Scholar
  45. Zuckerkandl E, Pauling L (1965) Evolutionary divergence and convergence in proteins. In: Bryson V, Vogel HJ (eds) Evolving genes and proteins. Academic Press, New York, pp 97–166Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1991

Authors and Affiliations

  • Tomoko Ohta
    • 1
  1. 1.National Institute of GeneticsMishimaJapan

Personalised recommendations