Adaptive evolution of cytochrome c oxidase subunit VIII in anthropoid primates

Allon Goldberg, Derek E. Wildman, Timothy R. Schmidt, Maik Hüttemann, Morris Goodman, Mark L. Weiss, Lawrence I. Grossman

Research output: Contribution to journalArticlepeer-review


Cytochrome c oxidase (COX) is a 13-subunit protein complex that catalyzes the last step in mitochondrial electron transfer in mammals. Of the 10 subunits encoded by nuclear DNA (three are mtDNA products), some are expressed as tissue- and/or development- specific isoforms. For COX subunit VIII, previous work showed that expression of the contractile muscle-specific isoform gene, COX8H, is absent in humans and Old World monkeys, and the other isoform gene, COX8L, is expressed ubiquitously. Here, we show that COX8H is transcribed in most primate clades, but its expression is absent in catarrhines, that is, in Old World monkeys and hominids (apes, including humans), having become a pseudogene in the stem of the catarrhines. The ubiquitously expressed isoform, COX8L, underwent nonsynonymous rate acceleration and elevation in the ratio of nonsynonymous/synonymous changes in the stem of anthropoid primates (New World monkeys and catarrhines), possibly setting the stage for loss of the heart-type (H) isoform. The most rapidly evolving region of VIII-L is one that interacts with COX I, suggesting that the changes are functionally coadaptive. Because accelerated rates of nonsynonymous substitutions in anthropoids such as observed for COX8L are also shown by genes for at least 13 other electron transport chain components, these encoded amino acid replacements may be viewed as part of a series of coadaptive changes that optimized the anthropoid biochemical machinery for aerobic energy metabolism. We argue that these changes were linked to the evolution of an expanded neocortex in anthropoid primates.

Original languageEnglish (US)
Pages (from-to)5873-5878
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - May 13 2003
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Adaptive evolution of cytochrome c oxidase subunit VIII in anthropoid primates'. Together they form a unique fingerprint.

Cite this