PREPONDERANCE OF SLIGHTLY DELETERIOUS POLYMORPHISM IN MITOCHONDRIAL-DNA - NONSYNONYMOUS SYNONYMOUS RATE RATIO IS MUCH HIGHER WITHIN SPECIESTHAN BETWEEN SPECIES/

We estimated synonymous (d(N)) and nonsynonymous (d(S)) substitution r ates for protein-coding genes of the mitochondrial genome from two ind ividuals each of the species human, chimpanzee, and gorilla. The genes were analyzed both separately and in a combined data set. Pairwise se quence comparisons suggest that the d(N)/d(S) rate ratios are about 5- 10 times higher in within-species comparisons than in between-species comparisons. This result is confirmed by a more rigorous likelihood ra tio test, which rejected the null hypothesis that the d(N)/d(S) rate r atios are identical within and between species. The Likelihood models account for the genetic code structure, transition/transversion rate r atio, and codon usage bias and are expected to produce more reliable r esults than the commonly used contingency test. Separate analyses of d ifferent genes show that the d(N)/d(S) rate ratios are higher within s pecies than between species for all 13 mitochondrial genes, with the d ifference being statistically significant for all except three small o r slowly evolving genes. Furthermore, in conserved genes, nonsynonymou s rates within species tend to be higher than the between-species rate s by a greater proportion than in fast-changing genes. Our findings co nfirm and extend earlier results obtained from smaller data sets and s uggest the operation of slightly deleterious mutations throughout the mitochondrial genome in the hominoids. Implications of the results for evolutionary studies and, in particular, for studies of the origin of modern humans, are discussed.