Neutrality tests of conservative-radical amino acid changes in nuclear- and mitochondrially-encoded proteins

Gene. 2000 Dec 30;261(1):115-25. doi: 10.1016/s0378-1119(00)00483-2.


The neutralist-selectionist debate should not be viewed as a dichotomy but as a continuum. While the strictly neutral model suggests a neutralist-selectionist dichotomy, the nearly neutral model is a continuous model spanning strict neutrality through weak selection (Ns approximately 1) to deterministic selection (Ns>3). We illustrate these points with polymorphism and divergence data from a sample of 73 genes (31 mitochondrial, 36 nuclear genes from Drosophila, and six Arabidopsis data sets). In an earlier study we used the McDonald-Kreitman (MK) test to show that amino acid replacement polymorphism in animal mitochondrial genes and Arabidopsis genes show a consistent trend toward negative selection, whereas nuclear genes from Drosophila span a range from negative selection, through neutrality, to positive selection. Here we analyze a subset of these genes (13 Drosophila nuclear, ten mitochondrial, and six Arabidopsis nuclear) for polymorphism and divergence of conservative and radical amino acid replacements (a protein-based conservative-radical MK, or pMK, test). The distinct patterns of selection between the different genomes is not apparent with the pMK test. Different definitions of conservative and radical (based on amino acid polarity, volume or charge) give inconsistent results across genes. We suggest that segregating fitness difference between silent and replacement mutations are more visible to selection than are segregating fitness differences between conservative and radical amino acid mutations. New data on the variation among genes with different opportunities for positive and negative selection are as important to the continuum view of the neutralist-selectionist debate as is the distribution of selection coefficients within individual genes.

Publication types

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

MeSH terms

  • Amino Acids / genetics*
  • Animals
  • Arabidopsis / genetics
  • Base Composition
  • Codon / genetics
  • Conserved Sequence
  • DNA, Mitochondrial / genetics*
  • Drosophila / genetics
  • Evolution, Molecular
  • Gene Frequency
  • Genes / genetics
  • Models, Genetic
  • Mutation
  • Nuclear Proteins / genetics*
  • Polymorphism, Genetic
  • Proteins / genetics*
  • Selection, Genetic


  • Amino Acids
  • Codon
  • DNA, Mitochondrial
  • Nuclear Proteins
  • Proteins