9700982 Lewontin ATP is the high-energy molecule used to drive nearly all metabolic processes and is produced in subcellular compartments called mitochondria, which have small circular DNA molecules determining some of the proteins required for its synthesis. The remainder of the proteins needed for ATP synthesis are specified in chromosomal DNA which resides in the nucleus. The pattern of mitochondrial DNA sequence change varies dramatically in related groups of vertebrate species, which could be due either to variation in mutation rate or to variation in functional constraint on proteins specified by that DNA. The funded research is intended to distinguish between these two hypotheses by examining the rate of DNA change in some of the nuclear (chromosomal) genes encoding proteins involved in ATP synthesis in these same vertebrate species. The mutational hypothesis predicts no relationship in rate of substitution between nuclear and mitochondrial genes, since the nuclear genes are not exposed to mitochondrial mutation rates, while the functional hypothesis does predict a relationship, since proteins responsible for ATP synthesis function in the same context irrespective of gene location. The distribution between nuclear and mitochondrial locations of the DNA specifying the proteins involved in ATP synthesis raises many interesting questions about the coordination of function of these proteins. This research explores one aspect of this coordination by asking whether patterns of similarity and difference in mitochondrial DNA sequence between species are echoed in functionally related nuclear DNA sequence between those same species. In addition, this research introducing a novel approach to the problem, one based on variation in rate of DNA sequence change.
