Epistatic interactions: how strong in disease and evolution?

Trends Genet. 2006 Nov;22(11):581-5. doi: 10.1016/j.tig.2006.08.001. Epub 2006 Sep 5.

Abstract

When the chimpanzee genome sequence was released, human deleterious alleles associated with simple mendelian diseases were observed as wild-type alleles in six genes (AIRE, MKKS, MLH1, MYOC, OTC and PRSS1). The absence of recognizable phenotypic effects in chimpanzee, contrary to the clinical effect observed in humans, is attributed to epistatic interactions (compensation) between potentially deleterious and compensatory alleles. In this report we investigate the possible evolutionary histories by which substitution of alternative variants in these six genes either ameliorates or avoids pathological consequences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AIRE Protein
  • Adaptation, Biological
  • Adaptor Proteins, Signal Transducing
  • Alleles
  • Animals
  • Biological Evolution*
  • Carrier Proteins / genetics
  • Cytoskeletal Proteins / genetics
  • Dosage Compensation, Genetic
  • Epistasis, Genetic*
  • Eye Proteins / genetics
  • Genetic Diseases, Inborn / genetics*
  • Glycoproteins / genetics
  • Group II Chaperonins
  • Humans
  • Models, Molecular
  • Molecular Chaperones / genetics
  • MutL Protein Homolog 1
  • Mutation
  • Nuclear Proteins / genetics
  • Pan troglodytes / genetics
  • Recombination, Genetic*
  • Transcription Factors / genetics
  • Trypsin
  • Trypsinogen / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Eye Proteins
  • Glycoproteins
  • MKKS protein, human
  • MLH1 protein, human
  • Molecular Chaperones
  • Nuclear Proteins
  • Transcription Factors
  • trabecular meshwork-induced glucocorticoid response protein
  • Trypsinogen
  • PRSS1 protein, human
  • Trypsin
  • Group II Chaperonins
  • MutL Protein Homolog 1