Bridging the gap between chemistry, physiology, and evolution: Quantifying the functionality of sperm whale myoglobin mutants
This work merges a large set of previously reported thermochemical data for myoglobin (Mb) mutants with a physiological model of O2-transport and -storage. The model allows a quantification of the functional proficiency of myoglobin (Mb) mutants under various physiological conditions, i.e. O2-consum...
| Published in: | Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology |
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| Main Authors: | , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
2011
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| Subjects: | |
| Online Access: | https://orbit.dtu.dk/en/publications/657df0a5-fb2b-4470-b0b7-dfc1a82a508b https://doi.org/10.1016/j.cbpa.2011.07.027 |
| Summary: | This work merges a large set of previously reported thermochemical data for myoglobin (Mb) mutants with a physiological model of O2-transport and -storage. The model allows a quantification of the functional proficiency of myoglobin (Mb) mutants under various physiological conditions, i.e. O2-consumption rate resembling workload, O2 partial pressure resembling hypoxic stress, muscle cell size, and Mb concentration, resembling different organism-specific and compensatory variables. We find that O2-storage and -transport are distinct functions that rank mutants and wild type differently depending on O2 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 O2-transporters because they still have empty sites for O2, giving rise to a larger [MbO2] 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 O2 pressure. These results together show that conserved residues in wild type (WT) Mb were fixated under a selection pressure of low PO2. |
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