An unusual amino acid substitution within hummingbird cytochrome c oxidase alters a key proton-conducting channel

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, yet exceedingly
rare 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 intriguing alteration encoded by the hummingbird
mitochondrial genome.