Biochemical Genetics

, Volume 38, Issue 5, pp 177–196

Functional Correlation in Amino Acid Residue Mutations of Yeast Iso-2-Cytochrome c that Is Consistent with the Prediction of the Concomitantly Variable Codon Theory in Cytochrome c Evolution

  • Alice Fisher
  • Ying Shi
  • Alice Ritter
  • James A. Ferretti
  • Gloria Perez-Lamboy
  • Mona Shah
  • Joseph Shiloach
  • Hiroshi Taniuchi
Article

DOI: 10.1023/A:1001977630789

Cite this article as:
Fisher, A., Shi, Y., Ritter, A. et al. Biochem Genet (2000) 38: 177. doi:10.1023/A:1001977630789

Abstract

Fitch and Markowitz' theory of concomitantly variable codons (covarions) in evolution predicted the existence of functional correlation in amino acid residue mutations among present-day cytochromes c. Mutational analysis was carried out on yeast iso-2-cytochrome c, where hydrophobic core residues I20, M64, L85, and M98 and surface residue L9 were mutated, in selected combinations, to those found in mammalian and bird cytochromes c. The functionality assay is based upon the ability of yeast cells to grow in YPGE medium. Furthermore, experiments on the single M64L and M98L mutations as well as the double M64L/M98L mutation using NMR showed that the effects of these mutations are to perturb the structural integrity of the protein. We identified functional correlation in two cases of a pair of residue mutations, the I20 → V and M98 → L pair and the L9 → I and L85 → I pair. In both cases, only one of the two alternative, putative evolutionary pathways leads to a functional protein and the corresponding pairs of residue mutations are among those found in present-day cytochromes c. Since valine is predicted to be at position 20 in the ancestral form of cytochrome c, the present data provide an explanation for the ancient requirement of leucine rather than methionine in position 98. The present data provide further evidence for the role of those specific atom–atom interactions in directing a pathway in the evolutionary changes of the amino acid sequence that have taken place in cytochrome c, in accordance with Fitch and Markowitz.

%cytochrome c evolutionfunctional correlationcovarion phenomenonyeast iso-2-cytochrome c mutation.

Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Alice Fisher
    • 1
  • Ying Shi
    • 1
  • Alice Ritter
    • 2
  • James A. Ferretti
    • 2
  • Gloria Perez-Lamboy
    • 1
  • Mona Shah
    • 1
  • Joseph Shiloach
    • 3
  • Hiroshi Taniuchi
    • 1
  1. 1.Laboratory of Chemical BiologyNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBethesda
  2. 2.Laboratory of Biophysical ChemistryNational Heart, Lung and Blood Institute, National Institutes of HealthBethesda
  3. 3.Laboratory of Cellular and Development BiologyNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBethesda