Rute da Fonseca
Molecular evolution in specific sets of genes
With Rasmus Nielsen @UCBerkeley and Agostinho Antunes @CiimarUp, I examined a number of gene sets in search for explanations of their apparently non-neutral evolution.
Proteins from the mitochondrial oxidative phosphorylation
I looked at the 12 proteins coded by mitochondrial DNA in 41 placental mammalian species [5]. These constitute subunits of the complexes involved in oxidative phosphorylation, a process responsible for producing up to 95% of a eukaryotic cell’s energy. These proteins are therefore under high functional constraints, but, since metabolic requirements vary across species, we have analyzed them looking for potentially modifying selective pressures, by assessing amino acid sequence variation and exploring the functional implications of observed variation in secondary and tertiary protein structures.
HAVCR1
I have also contributed to the understanding of the functional implications of positive selection in specific proteins detected by Kosiol et al [6] after performing a genome-wide scans for positively selected genes in 6 mammalian species. The positively selected sites found on HAVCR1, a cell-surface receptor for hepatitis A and other viruses, are present in regions of the protein believed to play critical roles in binding to viruses or in regulating the immune function of the gene.
Glutathione-transferases
I also investigated how the substrate specificity of glutathione transferases as been shaped by molecular evolution.Protection against oxidative stress seems to be the major driver of positive selection in on of gene-rich subfamilies (mammalian cGSTs).
Gene duplicates are maintained by: i) the diversification of endogenous substrates; ii) differential tissue expression; and iii) increased specificity for a particular molecule.
Apoptosis-related genes
Following the analysis of Kosiol et al [6], I looked at the relationship between the evolution in apoptosis-related genes and their role in diseases such as autoimmune disorders and cancer [7].