Phylogenetic analysis principles

Principles of phylogenetic analysis

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Further reading and resources

Powell et al. (2014) eggNOG v4.0: nested orthology inference across 3686 organisms. Nucleic Acids Res 42:D231-9. (pmid: 24297252)

[ PubMed ] [ DOI ] With the increasing availability of various 'omics data, high-quality orthology assignment is crucial for evolutionary and functional genomics studies. We here present the fourth version of the eggNOG database (available at http://eggnog.embl.de) that derives nonsupervised orthologous groups (NOGs) from complete genomes, and then applies a comprehensive characterization and analysis pipeline to the resulting gene families. Compared with the previous version, we have more than tripled the underlying species set to cover 3686 organisms, keeping track with genome project completions while prioritizing the inclusion of high-quality genomes to minimize error propagation from incomplete proteome sets. Major technological advances include (i) a robust and scalable procedure for the identification and inclusion of high-quality genomes, (ii) provision of orthologous groups for 107 different taxonomic levels compared with 41 in eggNOGv3, (iii) identification and annotation of particularly closely related orthologous groups, facilitating analysis of related gene families, (iv) improvements of the clustering and functional annotation approach, (v) adoption of a revised tree building procedure based on the multiple alignments generated during the process and (vi) implementation of quality control procedures throughout the entire pipeline. As in previous versions, eggNOGv4 provides multiple sequence alignments and maximum-likelihood trees, as well as broad functional annotation. Users can access the complete database of orthologous groups via a web interface, as well as through bulk download.

Wolf & Koonin (2012) A tight link between orthologs and bidirectional best hits in bacterial and archaeal genomes. Genome Biol Evol 4:1286-94. (pmid: 23160176)

[ PubMed ] [ DOI ] Orthologous relationships between genes are routinely inferred from bidirectional best hits (BBH) in pairwise genome comparisons. However, to our knowledge, it has never been quantitatively demonstrated that orthologs form BBH. To test this "BBH-orthology conjecture," we take advantage of the operon organization of bacterial and archaeal genomes and assume that, when two genes in compared genomes are flanked by two BBH show statistically significant sequence similarity to one another, these genes are bona fide orthologs. Under this assumption, we tested whether middle genes in "syntenic orthologous gene triplets" form BBH. We found that this was the case in more than 95% of the syntenic gene triplets in all genome comparisons. A detailed examination of the exceptions to this pattern, including maximum likelihood phylogenetic tree analysis, showed that some of these deviations involved artifacts of genome annotation, whereas very small fractions represented random assignment of the best hit to one of closely related in-paralogs, paralogous displacement in situ, or even less frequent genuine violations of the BBH-orthology conjecture caused by acceleration of evolution in one of the orthologs. We conclude that, at least in prokaryotes, genes for which independent evidence of orthology is available typically form BBH and, conversely, BBH can serve as a strong indication of gene orthology.

Salichos & Rokas (2011) Evaluating ortholog prediction algorithms in a yeast model clade. PLoS ONE 6:e18755. (pmid: 21533202)

[ PubMed ] [ DOI ] BACKGROUND: Accurate identification of orthologs is crucial for evolutionary studies and for functional annotation. Several algorithms have been developed for ortholog delineation, but so far, manually curated genome-scale biological databases of orthologous genes for algorithm evaluation have been lacking. We evaluated four popular ortholog prediction algorithms (MultiParanoid; and OrthoMCL; RBH: Reciprocal Best Hit; RSD: Reciprocal Smallest Distance; the last two extended into clustering algorithms cRBH and cRSD, respectively, so that they can predict orthologs across multiple taxa) against a set of 2,723 groups of high-quality curated orthologs from 6 Saccharomycete yeasts in the Yeast Gene Order Browser. RESULTS: Examination of sensitivity [TP/(TP+FN)], specificity [TN/(TN+FP)], and accuracy [(TP+TN)/(TP+TN+FP+FN)] across a broad parameter range showed that cRBH was the most accurate and specific algorithm, whereas OrthoMCL was the most sensitive. Evaluation of the algorithms across a varying number of species showed that cRBH had the highest accuracy and lowest false discovery rate [FP/(FP+TP)], followed by cRSD. Of the six species in our set, three descended from an ancestor that underwent whole genome duplication. Subsequent differential duplicate loss events in the three descendants resulted in distinct classes of gene loss patterns, including cases where the genes retained in the three descendants are paralogs, constituting 'traps' for ortholog prediction algorithms. We found that the false discovery rate of all algorithms dramatically increased in these traps. CONCLUSIONS: These results suggest that simple algorithms, like cRBH, may be better ortholog predictors than more complex ones (e.g., OrthoMCL and MultiParanoid) for evolutionary and functional genomics studies where the objective is the accurate inference of single-copy orthologs (e.g., molecular phylogenetics), but that all algorithms fail to accurately predict orthologs when paralogy is rampant.

Koonin (2005) Orthologs, paralogs, and evolutionary genomics. Annu Rev Genet 39:309-38. (pmid: 16285863)

[ PubMed ] [ DOI ] Orthologs and paralogs are two fundamentally different types of homologous genes that evolved, respectively, by vertical descent from a single ancestral gene and by duplication. Orthology and paralogy are key concepts of evolutionary genomics. A clear distinction between orthologs and paralogs is critical for the construction of a robust evolutionary classification of genes and reliable functional annotation of newly sequenced genomes. Genome comparisons show that orthologous relationships with genes from taxonomically distant species can be established for the majority of the genes from each sequenced genome. This review examines in depth the definitions and subtypes of orthologs and paralogs, outlines the principal methodological approaches employed for identification of orthology and paralogy, and considers evolutionary and functional implications of these concepts.