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

Dasmeh, Pouria; Kepp, Kasper Planeta

doi:10.1016/j.cbpa.2011.07.027

Cited by 20 publications

(24 citation statements)

References 39 publications

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“…In the present experiments, and similar to results from previous experiments (Pedersen et al, 2010), both O 2 consumption and twitch force were substantially lower at 9-12% O 2 than at 49% O 2 (see Table 1), indicating that the heart preparations were in a hypoxic state. This implies that Mb would be partly deoxygenated and thus that Mb-facilitated O 2 diffusion would be more critical (Gros et al, 2010;Dasmeh and Kepp, 2012). Our results agree with previous studies on fish and mammalian hearts (Bailey and Driedzic, 1986;Wittenberg and Wittenberg, 1989;Gros et al, 2010) in supporting an important role for Mb in maintaining mitochondrial O 2 consumption during hypoxia.…”

Section: Discussionsupporting

confidence: 93%

“…NOS inhibition removes the endogenous NO production, which in turn eliminates NO-scavenging by Mb and thus allows isolation of the role of Mb in O 2 supply. All experiments were performed under hypoxic conditions as previous studies (Bailey and Driedzic, 1986;Gros et al, 2010;Dasmeh and Kepp, 2012) have shown a significant role of Mb in O 2 supply only at low PO 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Mb facilitates intracellular O 2 diffusion by picking up O 2 near the cell membrane, traversing the cytosol, unloading O 2 near the mitochondria and diffusing back to the cell membrane to initiate another cycle (Wittenberg and Wittenberg, 1987), a mechanism that is especially important in linking O 2 supply from the blood with O 2 consumption in the muscle during hypoxia (Gros et al, 2010;Dasmeh and Kepp, 2012). Another important physiological role of Mb in the mammalian heart is to function as a dioxygenase enzyme and effectively scavenge reactive nitric oxide (NO) by oxidizing it into nitrate (Brunori, 2001;Flögel et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Myoglobin-dependent O2 consumption of the hypoxic trout heart

Helbo

Fago

Gesser

2013

Comparative Biochemistry and Physiology Part A: Molecular &

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Myoglobin-dependent O2 consumption of the hypoxic trout heart

Helbo

Fago

Gesser

2013

Comparative Biochemistry and Physiology Part A: Molecular &

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“…We used Mb as the model protein because its main functional phenotype (i.e., O 2 -binding as measured by the O 2 pressure at half Mb saturation [P 50 ]) is almost constant in mammals (Dasmeh and Kepp 2012), which is also reflected in the conservation of the important functional residues (Suzuki and Imai 1998; Scott et al 2000). Many of these sites are close to the heme group and are accordingly under strong purifying selection.…”

Section: Introductionmentioning

confidence: 99%

The Influence of Selection for Protein Stability on dN/dS Estimations

Dasmeh

Serohijos

Kepp

et al. 2014

Genome Biology and Evolution

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Understanding the relative contributions of various evolutionary processes—purifying selection, neutral drift, and adaptation—is fundamental to evolutionary biology. A common metric to distinguish these processes is the ratio of nonsynonymous to synonymous substitutions (i.e., dN/dS) interpreted from the neutral theory as a null model. However, from biophysical considerations, mutations have non-negligible effects on the biophysical properties of proteins such as folding stability. In this work, we investigated how stability affects the rate of protein evolution in phylogenetic trees by using simulations that combine explicit protein sequences with associated stability changes. We first simulated myoglobin evolution in phylogenetic trees with a biophysically realistic approach that accounts for 3D structural information and estimates of changes in stability upon mutation. We then compared evolutionary rates inferred directly from simulation to those estimated using maximum-likelihood (ML) methods. We found that the dN/dS estimated by ML methods (ωML) is highly predictive of the per gene dN/dS inferred from the simulated phylogenetic trees. This agreement is strong in the regime of high stability where protein evolution is neutral. At low folding stabilities and under mutation-selection balance, we observe deviations from neutrality (per gene dN/dS > 1 and dN/dS < 1). We showed that although per gene dN/dS is robust to these deviations, ML tests for positive selection detect statistically significant per site dN/dS > 1. Altogether, we show how protein biophysics affects the dN/dS estimations and its subsequent interpretation. These results are important for improving the current approaches for detecting positive selection.

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“…Besides O 2 storage and diffusion (Gros et al, 2010;Wittenberg and Wittenberg, 2003;Dasmeh and Kepp, 2012), other functions of Mb, associated with the protection against damaging effects of hypoxia and reoxygenation, have been discovered in recent years (Shiva et al, 2007;Hendgen-Cotta et al, 2008;Flögel et al, 2004). Specifically, deoxygenated Mb is able to reduce nitrite, an endogenous product of nitric oxide (NO) metabolism, to NO (Shiva et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Functional properties of myoglobins from five whale species with different diving capacities

Helbo

Fago

2012

Journal of Experimental Biology

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SUMMARYWhales show an exceptionally wide range of diving capabilities and many express high amounts of the O 2 carrier protein myoglobin (Mb) in their muscle tissues, which increases their aerobic diving capacity. Although previous studies have mainly focused on the muscle Mb concentration and O 2 carrying capacity as markers of diving behavior in whales, it still remains unexplored whether whale Mbs differ in their O 2 affinities and nitrite reductase and peroxidase enzymatic activities, all functions that could contribute to differences in diving capacities. In this study, we have measured the functional properties of purified Mbs from five toothed whales and two baleen whales and have examined their correlation with average dive duration. Results showed that some variation in functional properties exists among whale Mbs, with toothed whale Mbs having higher O 2 affinities and nitrite reductase activities (similar to those of horse Mb) compared with baleen whale Mbs. However, these differences did not correlate with average dive duration. Instead, a significant correlation was found between whale Mb concentration and average duration and depth of dives, and between O 2 affinity and nitrite reductase activity when including horse Mb. Despite the fact that the functional properties showed little species-specific differences in vitro, they may still contribute to enhancing diving capacity as a result of the increased muscle Mb concentration found in extreme divers. In conclusion, Mb concentration rather than specific functional reactivities may support whale diving performance.

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

Cited by 20 publications

References 39 publications

Myoglobin-dependent O2 consumption of the hypoxic trout heart

Myoglobin-dependent O2 consumption of the hypoxic trout heart

The Influence of Selection for Protein Stability on dN/dS Estimations

Functional properties of myoglobins from five whale species with different diving capacities

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