DEPARTURE FROM NEUTRALITY AT THE MITOCHONDRIAL NADH DEHYDROGENASE SUBUNIT-2 GENE IN HUMANS, BUT NOT IN CHIMPANZEES

To test whether patterns of mitochondrial DNA (mtDNA) variation are co nsistent with a neutral model of molecular evolution, nucleotide seque nces were determined for the 1041 bp of the NADH dehydrogenase subunit 2 (ND2) gene in 20 geographically diverse humans and 20 common chimpa nzees. Contingency tests of neutrality were performed using four mutat ional categories for the ND2 molecule: synonymous and nonsynonymous mu tations in the transmembrane regions, and synonymous and nonsynonymous mutations in the surface regions. The following three topological mut ational categories were also used: intraspecific tips, intraspecific i nteriors, and interspecific fixed differences. The analyses reveal a s ignificantly greater number of nonsynonymous polymorphisms within huma n transmembrane regions than expected based on interspecific compariso ns, and they are inconsistent with a neutral equilibrium model. This p at tern of excess nonsynonymous polymorphism is not seen within chimpa nzees. Statistical tests of neutrality, such as TAJIMA'S D test, and t he D and F tests proposed by FU and LI, indicate an excess of low freq uency polymorphisms in the human data, but not in the chimpanzee data. This is consistent with recent directional selection, a population bo ttleneck or background selection of slightly deleterious mutations in human mtDNA samples. The analyses further support the idea that mitoch ondrial genome evolution is governed by selective forces that have the potential to affect its use as a ''neutral'' marker in evolutionary a nd population genetic studies.