Journal Article

Revealing Mammalian Evolutionary Relationships by Comparative Analysis of Gene Clusters

Giltae Song, Cathy Riemer, Benjamin Dickins, Hie Lim Kim, Louxin Zhang, Yu Zhang, Chih-Hao Hsu, Ross C. Hardison, NISC Comparative Sequencing Program, Eric D. Green and Webb Miller

in Genome Biology and Evolution

Published on behalf of Society for Molecular Biology and Evolution

Volume 4, issue 4, pages 586-601
Published in print January 2012 |
Published online March 2012 | e-ISSN: 1759-6653 | DOI: https://dx.doi.org/10.1093/gbe/evs032

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Many software tools for comparative analysis of genomic sequence data have been released in recent decades. Despite this, it remains challenging to determine evolutionary relationships in gene clusters due to their complex histories involving duplications, deletions, inversions, and conversions. One concept describing these relationships is orthology. Orthologs derive from a common ancestor by speciation, in contrast to paralogs, which derive from duplication. Discriminating orthologs from paralogs is a necessary step in most multispecies sequence analyses, but doing so accurately is impeded by the occurrence of gene conversion events. We propose a refined method of orthology assignment based on two paradigms for interpreting its definition: by genomic context or by sequence content. X-orthology (based on context) traces orthology resulting from speciation and duplication only, while N-orthology (based on content) includes the influence of conversion events. We developed a computational method for automatically mapping both types of orthology on a per-nucleotide basis in gene cluster regions studied by comparative sequencing, and we make this mapping accessible by visualizing the output. All of these steps are incorporated into our newly extended CHAP 2 package. We evaluate our method using both simulated data and real gene clusters (including the well-characterized α-globin and β-globin clusters). We also illustrate use of CHAP 2 by analyzing four more loci: CCL (chemokine ligand), IFN (interferon), CYP2abf (part of cytochrome P450 family 2), and KIR (killer cell immunoglobulin-like receptors). These new methods facilitate and extend our understanding of evolution at these and other loci by adding automated accurate evolutionary inference to the biologist's toolkit. The CHAP 2 package is freely available from http://www.bx.psu.edu/miller_lab.

Keywords: gene clusters; orthology; conversion; evolutionary inference; KIR

Journal Article.  9536 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology ; Evolutionary Biology ; Genetics and Genomics

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