Bridging the gap between chemistry, physiology, and evolution: Quantifying the functionality of sperm whale myoglobin mutants

Abstract

This work merges a large set of previously reported thermochemical data for myoglobin (Mb) mutants with a physiological model of O 2-transport and -storage. The model allows a quantification of the functional proficiency of myoglobin (Mb) mutants under various physiological conditions, i.e. O 2-consumption rate resembling workload, O 2 partial pressure resembling hypoxic stress, muscle cell size, and Mb concentration, resembling different organism-specific and compensatory variables. We find that O 2-storage and -transport are distinct functions that rank mutants and wild type differently depending on O 2 partial pressure. Specifically, the wild type is near-optimal for storage at all conditions, but for transport only at severely hypoxic conditions. At normoxic conditions, low-affinity mutants are in fact better O 2-transporters because they still have empty sites for O 2, giving rise to a larger [MbO 2] gradient (more varying saturation curve). The distributions of functionality reveal that many mutants are near-neutral with respect to function, whereas only a few are strongly affected, and the variation in functionality increases dramatically at lower O 2 pressure. These results together show that conserved residues in wild type (WT) Mb were fixated under a selection pressure of low P O2.