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

The neutralist-selectionist debate should not be viewed as a dichotomy but as a continuum. While the strictly neutral model suggests a neutralist-sele ctionist dichotomy, the nearly neutral model is a continuous model spanning strict neutrality through weak selection (Ns similar to 1) to deterministi c selection (Ns > 3). We illustrate these points with polymorphism and dive rgence data from a sample of 73 genes (31 mitochondrial, 36 nuclear genes f rom Drosophila, and six Arabidopsis data sets). In an earlier study we used the McDonald-Kreitman (MK) test to show that amino acid replacement polymo rphism in animal mitochondrial genes and Arabidopsis genes show a consisten t trend toward negative selection, whereas nuclear genes from Drosophila sp an a range from negative selection, through neutrality, to positive selecti on. Here we analyze a subset of these genes (13 Drosophila nuclear, ten mit ochondrial, and six Arabidopsis nuclear) for polymorphism and divergence of conservative and radical amino acid replacements (a protein-based conserva tive-radical MK, or pMK, test). The distinct patterns of selection between the different genomes is not apparent with the pMK test. Different definiti ons of conservative and radical (based on amino acid polarity volume or cha rge) give inconsistent results across genes. We suggest that segregating fi tness difference between silent and replacement mutations are more visible to selections than are segregating fitness differences between conservative and radical amino acid and replacement mutations are more visible to selec tion than are segregating fitness differences between conservative and radi cal amino acid mutations. New data on the variation among genes with differ ent opportunities for positive and negative selection are as important to t he continuum view of the neutralist-selectionist debate as is the distribut ion of selection coefficients within individual genes. (C) 2000 Elsevier Sc ience B.V. All rights reserved.