Understanding the meaning of protein sequence evolution.
Barry Williams, Jayne Selegue, Sean Carroll
Lab of Molecular Biology, University of Wisconsin, 1525 Linden Dr., Madison, WI, 53706, USA
There is currently a disconnect among biologists as to the meaning of protein sequence divergence. Evolutionary biologists debate whether amino acid replacements are neutral, nearly neutral, or fixed by selection. Molecular biologists study mutations in conserved sites with large fitness effects, but have not considered the functional contribution of non-conserved sites. Ecologists measure large selection coefficients on natural phenotypic variation, but have yet to understand the nature of the underlying mutations. One common element that is missing is knowledge of the fitness effects of amino acid replacements fixed among species during evolutionary divergence. The evolution of yeasts in the genus Saccharomyces provides a unique opportunity to examine such effects. We created several orthologous gene replacements and developed a sensitive competition assay to measure their relative fitness in vivo. The data show that even large numbers of substitutions are collectively of slight effect and could only be fixed by selection in very large populations.
Return to YGM 2004 Home at SGD