title: 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).
authors: Technical University of Denmark, DTU Chemistry, Kemitorvet 206, Kongens Lyngby, Denmark.
authors: Pouria
authors: P
authors: Dasmeh
authors: Kasper P
authors: KP
authors: Kepp
mesh_terms: D000818:Animals; D004242:Diving / Q000502:physiology*; D019143:Evolution, Molecular; D006801:Humans; D032342:Muscle Cells / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D009211:Myoglobin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D010313:Partial Pressure; D012641:Selection, Genetic; D050661:Sperm Whale; D014907:Whales / Q000378:metabolism / Q000502:physiology*
chemical_list: D009211:Myoglobin; D010100:Oxygen