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Example: Ortholog Prediction

Example: Ortholog Prediction. Orthologs : two genes related by speciation events alone. “the same gene in two species”, typically, same function . Paralogs : two genes related by at least one gene-duplication & divergence event. Homology: an ortholog or a paralog?

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Example: Ortholog Prediction

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  1. Example: Ortholog Prediction • Orthologs: two genes related by speciation events alone. “the same gene in two species”, typically, same function. • Paralogs: two genes related by at least one gene-duplication & divergence event. Homology: an ortholog or a paralog? • Experimentally very hard to answer.

  2. Gene Evolution through Speciation vs. Duplication speciation gene duplication orthologs paralogs

  3. Using Multiple Genomes for Ortholog Cross-Validation • Within a given genome, ortholog should be more similar than paralog (same time of divergence, but divergent functional pressure on paralog). • Completegenome: if there’s an ortholog, you’ll find it! • Multiple genomes: quickly sort out lack-of-ortholog, multiple paralogs, gene-loss problems that could lead you astray.

  4. Cluster of Orthologous Genes Orthologs should be reciprocal best hits. ? Tatusov, Koonin & Lipman, Science278, 631 (1997)

  5. Reciprocal Best Hits Indicate Orthologs Reciprocal best hit Non-reciprocal best hit

  6. Multiple Genomes Screen Out Errors True orthologs should give consistent, reciprocal best-hit pattern as more genomes added. ? Chance of missing a true ortholog, or predicting an incorrect “ortholog”, exponentially decrease as more genomes added.

  7. Simple Ortholog Cluster (found in three genomes) KatG YKR066c sII1987 Catalase peroxidase in E. coli, yeast, Synechocystis, from Tatusov, Koonin & Lipman, Science278, 631 (1997)

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