A Parsimony Approach to Genome-Wide Ortholog Assignment
The assignment of orthologous genes between a pair of genomes is a fundamental and challenging problem in comparative genomics, since many computational methods for solving various biological problems critically rely on bona fide orthologs as input. While it is usually done using sequence similarity search, we recently proposed a new combinatorial approach that combines sequence similarity and genome rearrangement. This paper continues the development of the approach and unites genome rearrangement events and (post-speciation) duplication events in a single framework under the parsimony principle. In this framework, orthologous genes are assumed to correspond to each other in the most parsimonious evolutionary scenario involving both genome rearrangement and (post-speciation) gene duplication. Besides several original algorithmic contributions, the enhanced method allows for the detection of inparalogs. Following this approach, we have implemented a high-throughput system for ortholog assignment on a genome scale, called MSOAR, and applied it to the genomes of human and mouse. As the result will show, MSOAR is able to find 99 more true orthologs than the INPARANOID program did. We have also compared MSOAR with the iterated exemplar algorithm on simulated data and found that MSOAR performed very well in terms of assignment accuracy. These test results indiate that our approach is very promising for genome-wide ortholog assignment.
KeywordsGene Pair Genome Rearrangement Ancestral Genome Ortholog Pair Orthologous Gene Pair
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- 2.Bairoch, A., et al.: The Universal Protein Resource (UniProt). Nuc. Acids Res. 33, D154–D159 (2005)Google Scholar
- 4.Chen, X., Zheng, J., Fu, Z., Nan, P., Zhong, Y., Lonardi, S., Jiang, T.: Computing the assignment of orthologous genes via genome rearrangement. In: Proc. 3rd Asia Pacific Bioinformatics Conf (APBC 2005), pp. 363–378 (2005)Google Scholar
- 7.Hannenhalli, S., Pevzner, P.: Transforming cabbage into turnip (polynomial algorithm for sorting signed permutations by reversals). In: Proc. 27th Ann. ACM Symp. Theory of Comput (STOC 1995), pp. 178–189 (1995)Google Scholar
- 8.Hannenhalli, S., Pevzner, P.: Transforming men into mice (polynomial algorithm for genomic distance problem). In: Proc. IEEE 36th Symp. Found. of Comp. Sci, pp. 581–592 (1995)Google Scholar
- 10.Koonin, E.: Orthologs, paralogs, and evolutionary genomics. In: Annu. Rev. Genet. (2005)Google Scholar
- 18.Swenson, K., Marron, M., Earnest-DeYoung, J., Moret, B.: Approximating the true evolutionary distance between two genomes. In: Proc. 7th SIA Workshop on Algorithm Engineering & Experiments, pp. 121–125 (2005)Google Scholar
- 20.Storm, C., Sonnhammer, E.: Automated ortholog inference from phylogenetic trees and calculation of orthology reliability. Bioinformatics 18(1) (2002)Google Scholar