Journal of Molecular Evolution

, Volume 59, Issue 3, pp 329–339 | Cite as

Comparative Genetics of Functional Trinucleotide Tandem Repeats in Humans and Apes

  • Aida M. Andrés
  • Marta Soldevila
  • Oscar Lao
  • Víctor Volpini
  • Naruya Saitou
  • Howard T Jacobs
  • Ikuo Hayasaka
  • Francesc Calafell
  • Jaume BertranpetitEmail author


Several human neurodegenerative disorders are caused by the expansion of polymorphic trinucleotide repeat regions. Many of these loci are functional short tandem repeats (STRs) located in brain-expressed genes, and their study is thus relevant from both a medical and an evolutionary point of view. The aims of our study are to infer the comparative pattern of variation and evolution of this set of loci in order to show species-specific features in this group of STRs and on their potential for expansion (therefore, an insight into evolutionary medicine) and to unravel whether any human-specific feature may be identified in brain-expressed genes involved in human disease. We analyzed the variability of the normal range of seven expanding STR CAG/CTG loci (SCA1, SCA2, SCA3-MJD, SCA6, SCA8, SCA12, and DRPLA) and two nonexpanding polymorphic CAG loci (KCNN3 and NCOA3) in humans, chimpanzees, gorillas, and orangutans. The study showed a general conservation of the repetitive tract and of the polymorphism in the four species and high heterogeneity among loci distributions. Humans present slightly larger alleles than the rest of species but a more relevant difference appears in variability levels: Humans are the species with the largest variance, although only for the expanding loci, suggesting a relationship between variability levels and expansion potential. The sequence analysis shows high levels of sequence conservation among species, a lack of correspondence between interruption patterns and variability levels, and signs of conservative selective pressure for some of the STR loci. Only two loci (SCA1 and SCA8) show a human specific distribution, with larger alleles than the rest of species. This could account, at the same time, for a human-specific trait and a predisposition to disease through expansion.


Spinocerebellar ataxia Trinucleotide repeat expansion Short tandem repeat evolution Primates 



We thank Monica Vallés for her technical support and Anna Pérez-Lezaun for her technical help and feedback. The authors would like to especially thank Arcadi Navarro for reading the manuscript and for his help with statistical comparisons, Michael Greenacre for statistical help, Lynn B. Jorde, Pascal Gagneux, and Mar Albà for reading an early version of the manuscript, and Lynda Vigilant, Pascal Gagneux, and Anne C. Stone for helpful advice on primate subspecies determination. Tanzanian human samples were kindly supplied by Dr. Clara Menéndez from the Unitat d’Epidemiologia i Bioestadística (Hospital Clínic, Barcelona). Primate samples were supplied by the Barcelona Zoo (under the agreement of the Primate DNA Bank with the Pompeu Fabra University), Ikuo Hayasaka, and Dr. Takafumi Ishida of the University of Tokyo (Japan) or obtained from the Institute of Zoology (London), Coriell Cell Repositories (CCR), and European Collection of Cell Cultures (ECACC). This study was supported by the Dirección General de Investigación (Spanish Goverment), Grants SAF 2001-0772 to J.B. and BOS2001-0794 to F.C., and Grants-in-Aids to Priority Area from MEXT, Japan, to N.S. A.M.A. was financially supported by a fellowship from Generalitat de Catalunya, 2000FI 00686.

Supplementary material

s00239-004-2628-5_esm.pdf (159 kb)
Additional Information.


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Aida M. Andrés
    • 1
  • Marta Soldevila
    • 1
  • Oscar Lao
    • 1
  • Víctor Volpini
    • 2
  • Naruya Saitou
    • 3
  • Howard T Jacobs
    • 4
  • Ikuo Hayasaka
    • 5
  • Francesc Calafell
    • 1
  • Jaume Bertranpetit
    • 1
    Email author
  1. 1.Unitat de Biologia Evolutiva, Facultat de Ciències de la Salut i de la VidaUniversitat Pompeu FabraBarcelonaSpain
  2. 2.Molecular Genetics DepartmentCancer Research Institute BarcelonaSpain
  3. 3.Division of Population GeneticsNational Institute of GeneticsMishimaJapan
  4. 4.Institute of Medical Technology and Tampere University HospitalUniversity of TampereTampereFinland
  5. 5.Sanwa Kagaku, Kenkyusho Kumamoto Primate ParkMisumiJapan

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