Identifying orthologs with OMA: A primer

Abstract

The Orthologous Matrix (OMA) is a method and database that allows users to identify orthologs among many genomes. OMA provides three different types of orthologs: pairwise orthologs, OMA Groups and Hierarchical Orthologous Groups (HOGs). This Primer is organized in two parts. In the first part, we provide all the necessary background information to understand the concepts of orthology, how we infer them and the different subtypes of orthology in OMA, as well as what types of analyses they should be used for. In the second part, we describe protocols for using the OMA browser to find a specific gene and its various types of orthologs. By the end of the Primer, readers should be able to (i) understand homology and the different types of orthologs reported in OMA, (ii) understand the best type of orthologs to use for a particular analysis; (iii) find particular genes of interest in the OMA browser; and (iv) identify orthologs for a given gene. The data can be freely accessed from the OMA browser at https://omabrowser.org.

Keywords: Comparative genomics; Hierarchical orthologous groups; OMA; Orthologous Matrix; orthology; phylogenetics.

Figure 1.. How the OMA algorithm infers pairwise orthologs.

Figure 2.. An example of OMA’s inference of pairwise orthologs, HOGs, and OMA Groups.

The species tree and genomes are used as input for the OMA pipeline ( A– B), which results initially in pairs of orthologs ( D). The pairwise orthologs are then used to build orthologous groups ( E), which are subsequently clustered into HOGs ( F) or OMA Groups ( G). Each grouping method results in slightly different pairs of orthologs ( D, H, I).

Figure 3.. An example set of nested HOGs (HOGs 1–3).

( A) A hypothetical gene tree between a gene family in three different species. Each node on this reconciled gene tree is either a speciation node or a duplication node (star). HOGs are formed at each taxonomic level, two HOGs at the mammalian level, and one at the tetrapoda level. ( B) HOG-derived ortholog pairs at each taxonomic level. At the tetrapod level, the ortholog pairs are more numerous. One common pitfall may be to incorrectly infer an orthologous pair at the tetropoda level between the blue dog gene and the red human gene. However, these genes can be traced back to a duplication event rather than a speciation event, and thus are paralogs. The HOG-derived orthologs at the mammalian level are more fine-grained because the duplication event has already taken place.

Figure 4.. Searching for a gene identifier using the OMA browser.

Figure 5.. Gene information for the human S100P gene in OMA.

Shown are the General Information and IDs and Cross-references sections in the Information tab on the OMA browser. This tab also contains the Domain Architecture, Gene Ontology, Protein Sequence and Coding Sequence sections (not shown).

Figure 6.. OMA rat p53 gene entry.

Tabs located under the heading link to orthologs. From left to right: ‘Orthologs’ links to pairwise orthologs and indicates the number of orthologs, ‘Hierarchical Orthologous Groups’ to HOGs, and ‘OMA Groups’ to OMA Groups.

Figure 7.. Partial list of pairwise orthologs for the rat p53 gene entry in OMA.

Figure 8.. Partial list of orthologs in OMA group containing the rat p53 gene entry.

Figure 9.. Partial list of members of the HOG containing the rat p53 gene entry open at level of Chordata.

Figure 10.. Orthology inference plays a central role in a variety of genomic analyses.

Reproduced from Glover et al. , Advances and Applications in the Quest for Orthologs, Molecular Biology and Evolution, msz150.

Figure 11.. Comparison of pairwise, HOG-derived orthologs and OMA group-derived orthologs for the rat p53 gene entry.

RATNO03710 (P53_RAT) is found in both the root-level OMA HOG:0430403 and OMA Group RCPHHQS, but is obviously not listed in the pairwise orthologs. It has thus been excluded from the comparison.