Limits...
The adaptive evolution of the mammalian mitochondrial genome.

da Fonseca RR, Johnson WE, O'Brien SJ, Ramos MJ, Antunes A - BMC Genomics (2008)

Bottom Line: ATP6, which has an essential role in rotor performance, showed a high adaptive variation in predicted loop areas.Our study provides insight into the adaptive evolution of the mtDNA genome in mammals and its implications for the molecular mechanism of oxidative phosphorylation.We present a framework for future experimental characterization of the impact of specific mutations in the function, physiology, and interactions of the mtDNA encoded proteins involved in oxidative phosphorylation.

View Article: PubMed Central - HTML - PubMed

Affiliation: REQUIMTE, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal. rute.r.da.fonseca@gmail.com

ABSTRACT

Background: The mitochondria produce up to 95% of a eukaryotic cell's energy through oxidative phosphorylation. The proteins involved in this vital process are under high functional constraints. However, metabolic requirements vary across species, potentially modifying selective pressures. We evaluate the adaptive evolution of 12 protein-coding mitochondrial genes in 41 placental mammalian species by assessing amino acid sequence variation and exploring the functional implications of observed variation in secondary and tertiary protein structures.

Results: Wide variation in the properties of amino acids were observed at functionally important regions of cytochrome b in species with more-specialized metabolic requirements (such as adaptation to low energy diet or large body size, such as in elephant, dugong, sloth, and pangolin, and adaptation to unusual oxygen requirements, for example diving in cetaceans, flying in bats, and living at high altitudes in alpacas). Signatures of adaptive variation in the NADH dehydrogenase complex were restricted to the loop regions of the transmembrane units which likely function as protons pumps. Evidence of adaptive variation in the cytochrome c oxidase complex was observed mostly at the interface between the mitochondrial and nuclear-encoded subunits, perhaps evidence of co-evolution. The ATP8 subunit, which has an important role in the assembly of F0, exhibited the highest signal of adaptive variation. ATP6, which has an essential role in rotor performance, showed a high adaptive variation in predicted loop areas.

Conclusion: Our study provides insight into the adaptive evolution of the mtDNA genome in mammals and its implications for the molecular mechanism of oxidative phosphorylation. We present a framework for future experimental characterization of the impact of specific mutations in the function, physiology, and interactions of the mtDNA encoded proteins involved in oxidative phosphorylation.

Show MeSH

Related in: MedlinePlus

Rotary model for E. coli F1F0 ATPase and variation in the mammalian ATP6 subunit. A) Rotary model for E. coli F1F0 ATPase (see text for details); B) Topological assignment of the sites that present a high number of strong positively selected amino acid properties under positive-destabilizing selection in ATP6 (corresponds to the a subunit in E. coli). The transmembrane domains location is shown in grey (for details see Material and Methods section). The dark grey domain was only predicted by one of the three methods used.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2375446&req=5

Figure 12: Rotary model for E. coli F1F0 ATPase and variation in the mammalian ATP6 subunit. A) Rotary model for E. coli F1F0 ATPase (see text for details); B) Topological assignment of the sites that present a high number of strong positively selected amino acid properties under positive-destabilizing selection in ATP6 (corresponds to the a subunit in E. coli). The transmembrane domains location is shown in grey (for details see Material and Methods section). The dark grey domain was only predicted by one of the three methods used.

Mentions: The proton-gradient that results from H+ pumping into the intermembrane space, is used by ATPase to synthesize ATP. The proton channel is located in the membrane sector (F0) which is connected to the catalytic component (F1), located on the matrix side of the membrane (Figure 12A). The latter, when separated from the membrane, behaves as a soluble ATPase. Large cooperative conformational changes occur in order to couple the passage of protons through the membrane arm and the production of ATP [47,48]. In the proposed mechanism for E. coli ATPase, protons that have accumulated in the periplasm enter the assembly via subunit a (corresponding to ATP6 in yeast [49]). One proton binds between two c subunits (corresponding to ATP9 subunits in yeast [49]). In order for the proton to reach the exit channel, the c subunits (in a total of 10 in E. coli), that are arranged as a cylinder, have to rotate, releasing the proton after 10 steps of proton binding. This rotation movement involves the γ and ε subunits, that remain fixed to the top of one set of c subunits. The rotation of γ within the α/β subunits induces conformational changes that release ATP from the alternating catalytic cycles. The ε subunit (homologous to mitochondrial subunit δ and IF1 regulatory protein) is responsible for determining whether complex V acts as a synthase or catalyses the reverse reaction (pumping protons from the cytoplasm/matrix to the periplasm/intermembrane space) at the expenses of ATP hydrolysis. Subunits b and δ (equivalent to mitochondrial OSCP) keep the α/β subunits in a fixed position. The conservation of ATP6 reflects its key role in the coupling of the proton flow with the rotation of the c subunits: as for the ND complex, the sites with higher variation are located only in the predicted loop regions (Figure 12B).


The adaptive evolution of the mammalian mitochondrial genome.

da Fonseca RR, Johnson WE, O'Brien SJ, Ramos MJ, Antunes A - BMC Genomics (2008)

Rotary model for E. coli F1F0 ATPase and variation in the mammalian ATP6 subunit. A) Rotary model for E. coli F1F0 ATPase (see text for details); B) Topological assignment of the sites that present a high number of strong positively selected amino acid properties under positive-destabilizing selection in ATP6 (corresponds to the a subunit in E. coli). The transmembrane domains location is shown in grey (for details see Material and Methods section). The dark grey domain was only predicted by one of the three methods used.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2375446&req=5

Figure 12: Rotary model for E. coli F1F0 ATPase and variation in the mammalian ATP6 subunit. A) Rotary model for E. coli F1F0 ATPase (see text for details); B) Topological assignment of the sites that present a high number of strong positively selected amino acid properties under positive-destabilizing selection in ATP6 (corresponds to the a subunit in E. coli). The transmembrane domains location is shown in grey (for details see Material and Methods section). The dark grey domain was only predicted by one of the three methods used.
Mentions: The proton-gradient that results from H+ pumping into the intermembrane space, is used by ATPase to synthesize ATP. The proton channel is located in the membrane sector (F0) which is connected to the catalytic component (F1), located on the matrix side of the membrane (Figure 12A). The latter, when separated from the membrane, behaves as a soluble ATPase. Large cooperative conformational changes occur in order to couple the passage of protons through the membrane arm and the production of ATP [47,48]. In the proposed mechanism for E. coli ATPase, protons that have accumulated in the periplasm enter the assembly via subunit a (corresponding to ATP6 in yeast [49]). One proton binds between two c subunits (corresponding to ATP9 subunits in yeast [49]). In order for the proton to reach the exit channel, the c subunits (in a total of 10 in E. coli), that are arranged as a cylinder, have to rotate, releasing the proton after 10 steps of proton binding. This rotation movement involves the γ and ε subunits, that remain fixed to the top of one set of c subunits. The rotation of γ within the α/β subunits induces conformational changes that release ATP from the alternating catalytic cycles. The ε subunit (homologous to mitochondrial subunit δ and IF1 regulatory protein) is responsible for determining whether complex V acts as a synthase or catalyses the reverse reaction (pumping protons from the cytoplasm/matrix to the periplasm/intermembrane space) at the expenses of ATP hydrolysis. Subunits b and δ (equivalent to mitochondrial OSCP) keep the α/β subunits in a fixed position. The conservation of ATP6 reflects its key role in the coupling of the proton flow with the rotation of the c subunits: as for the ND complex, the sites with higher variation are located only in the predicted loop regions (Figure 12B).

Bottom Line: ATP6, which has an essential role in rotor performance, showed a high adaptive variation in predicted loop areas.Our study provides insight into the adaptive evolution of the mtDNA genome in mammals and its implications for the molecular mechanism of oxidative phosphorylation.We present a framework for future experimental characterization of the impact of specific mutations in the function, physiology, and interactions of the mtDNA encoded proteins involved in oxidative phosphorylation.

View Article: PubMed Central - HTML - PubMed

Affiliation: REQUIMTE, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal. rute.r.da.fonseca@gmail.com

ABSTRACT

Background: The mitochondria produce up to 95% of a eukaryotic cell's energy through oxidative phosphorylation. The proteins involved in this vital process are under high functional constraints. However, metabolic requirements vary across species, potentially modifying selective pressures. We evaluate the adaptive evolution of 12 protein-coding mitochondrial genes in 41 placental mammalian species by assessing amino acid sequence variation and exploring the functional implications of observed variation in secondary and tertiary protein structures.

Results: Wide variation in the properties of amino acids were observed at functionally important regions of cytochrome b in species with more-specialized metabolic requirements (such as adaptation to low energy diet or large body size, such as in elephant, dugong, sloth, and pangolin, and adaptation to unusual oxygen requirements, for example diving in cetaceans, flying in bats, and living at high altitudes in alpacas). Signatures of adaptive variation in the NADH dehydrogenase complex were restricted to the loop regions of the transmembrane units which likely function as protons pumps. Evidence of adaptive variation in the cytochrome c oxidase complex was observed mostly at the interface between the mitochondrial and nuclear-encoded subunits, perhaps evidence of co-evolution. The ATP8 subunit, which has an important role in the assembly of F0, exhibited the highest signal of adaptive variation. ATP6, which has an essential role in rotor performance, showed a high adaptive variation in predicted loop areas.

Conclusion: Our study provides insight into the adaptive evolution of the mtDNA genome in mammals and its implications for the molecular mechanism of oxidative phosphorylation. We present a framework for future experimental characterization of the impact of specific mutations in the function, physiology, and interactions of the mtDNA encoded proteins involved in oxidative phosphorylation.

Show MeSH
Related in: MedlinePlus