Epistatic interactions modulate the evolution of mammalian mitochondrial respiratory complex components

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Luisa Azevedo (Author) Other; Joao Carneiro (Author) Other; Barbara van Asch (Author) Other; Ana Moleirinho (Author) Other; Filipe Pereira (Author) Other; Antonio Amorim (Author) FCUP

Journal

Title: BMC Genomics

Vol. 10

Final page: 266

ISSN: 1471-2164

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 31 Citations

Scopus - 29 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-003-J89

DOI: 10.1186/1471-2164-10-266

Abstract (EN): Background: The deleterious effect of a mutation can be reverted by a second-site interacting residue. This is an epistatic compensatory process explaining why mutations that are deleterious in some species are tolerated in phylogenetically related lineages, rendering evident that those mutations are, by all means, only deleterious in the species-specific context. Although an extensive and refined theoretical framework on compensatory evolution does exist, the supporting evidence remains limited, especially for protein models. In this current study, we focused on the molecular mechanism underlying the epistatic compensatory process in mammalian mitochondrial OXPHOS proteins using a combination of in-depth structural and sequence analyses. Results: Modeled human structures were used in this study to predict the structural impairment and recovery of deleterious mutations alone and combined with an interacting compensatory partner, respectively. In two cases, COI and COIII, intramolecular interactions between spatially linked residues restore the folding pattern impaired by the deleterious mutation. In a third case, intermolecular contact between mitochondrial CYB and nuclear CYT I encoded components of the cytochrome bc I complex are likely to restore protein binding. Moreover, we observed different modes of compensatory evolution that have resulted in either a quasi-simultaneous occurrence of a mutation and corresponding compensatory partner, or in independent occurrences of mutations in distinct lineages that were always preceded by the compensatory site. Conclusion: Epistatic interactions between individual replacements involving deleterious mutations seems to follow a parsimonious model of evolution in which genomes hold precompensating states that subsequently tolerate deleterious mutations. This phenomenon is likely to have been constraining the variability at coevolving sites and shaping the interaction between the mitochondrial and the nuclear genome.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12