Domain architecture conservation in orthologs

by Mr Kristoffer Forslund (Stockholm Bioinformatics Centre)

Wednesday 2 Jun 2010, 16:00 → 17:00 Europe/Stockholm

RB35 (RB35)

As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional transfer between species. However, ortholog identification methods do not take changes in domain architecture into account, which are likely to modulate a protein's function.

To assess the level of domain architectural changes among orthologs we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. Using orthology status predicted by InParanoid, we applied a measure of domain architecture similarity designed for this purpose to both orthologs and non-orthologs and contrasted the resulting scores with the fraction of identical aligned residues between the sequences. We also statistically characterized the type and extent of domain swapping events for orthologous as well as for non-orthologous proteins.

The analysis shows that orthologs as well as the closest non-orthologous homologs generally have very similar domain architectures, even at large evolutionary separation, whereas sequence identity decreases much more rapidly. We demonstrate that orthologs exhibit greater conservation of domain architecture than close non-orthologous homologs, even at equivalent separation with regards to sequence identity. We interpret this as an indication of a selective pressure on orthologs, but not paralogs, to specifically retain domain architecture, required for the proteins to perform their conserved function.