RT Journal Article SR Electronic T1 An unusual amino acid substitution within hummingbird cytochrome c oxidase alters a key proton-conducting channel JF bioRxiv FD Cold Spring Harbor Laboratory SP 610915 DO 10.1101/610915 A1 Cory D. Dunn A1 Bala Anı Akpınar A1 Vivek Sharma YR 2020 UL http://biorxiv.org/content/early/2020/05/14/610915.abstract AB Hummingbirds in flight exhibit the highest metabolic rate of all vertebrates. The bioenergetic requirements associated with sustained hovering flight raise the possibility of unique amino acid substitutions that would enhance aerobic metabolism. Here, we have identified a non-conservative substitution within the mitochondria-encoded cytochrome c oxidase subunit I (COI) that is fixed within hummingbirds, but not among other vertebrates. This unusual change is also rare among metazoans, but can be identified in several clades with diverse life histories. We performed atomistic molecular dynamics simulations using bovine and hummingbird COI models, thereby bypassing experimental limitations imposed by the inability to modify mtDNA in a site-specific manner. Intriguingly, our findings suggest that COI amino acid position 153 (bovine numbering system) provides control over the hydration and activity of a key proton channel in COX. We discuss potential phenotypic outcomes linked to this alteration encoded by the hummingbird mitochondrial genome.Competing Interest StatementThe authors have declared no competing interest.