Verifying Orthologous Paralogenes using Whole Genome Alignment

Identifying orthologous paralogenes is a fundamental problem in comparative genomics and can facilitate the study of evolutionary history of the species. Existing approaches for locating paralogs make use of local alignment based algorithms such as BLAST. However, there are cases that genes with high alignment scores are not paralogenes. On the other hand, whole genome alignment tools are designed to locate orthologs. Most of these tools are based on some unique substrings (called anchors) in the corresponding orthologous pair to identify them. Intuitively, these tools may not be useful in identifying orthologous paralogenes as paralogenes are very similar and there may not be enough unique anchors. However, our study shows that this is not true. Paralogenes although are similar, they have undergone different mutations. So, there are enough unique anchors for identifying them. Our contributions include the followings. Based on this counter-intuitive finding, we propose to employ the whole genome alignment tools to help verifying paralogenes. Our experiments on five pairs of human-mouse chromosomes show that our approach is effective and can identify most of the mis-classified paralog groups (more than 80%). We verify our finding that whole genome alignment tools are able to locate orthologous paralogenes through a simulation study. The result from the study confirms our finding.