“Natural History” of Ascomycota fungi

November 13, 2007

Nature recently published a paper by Wapinski et. al. entitled “Natural history and evolutionary principles of gene duplication in fungi.”. This was a follow up paper to their ISMB paper “Automatic genome-wide reconstruction of phylogenetic gene trees.” Bioinformatics, 23(13), i549-i558 (2007). DOI: 10.1093/bioinformatics/btm193. In these papers the authors seek to answer the following questions:

  1. How does one clearly identify orthologs?
  2. What genes share a common ancestor?
  3. What happened to them along the way?

The algorithm (SYNERGY) uses sequence similarity, gene order and a given species tree (phylogeny) to reconstruct the underlying evolutionary history of all genes in a large group of species. They define orthogroups as sets of genes in extant species that trace their ancestry to a single gene in the last common ancestor. Their methodology for gene tree construction uses a bottom up greedy approach to identify orthogroups. They do a reasonable job at orthogroup completeness (sensitivity) by allowing many edges in their candidate homology graph (a loose definition of homology). They balance this with soundness of orthogroups (specificity) by refining the coarse relations as they progress through the species tree (a given) … breaking orthogroups in a phylogenetically sound fashion.

This work can be viewed as an extension to the phylogenetic ortholog/paralog resolution work of Christian Zmasek’s (and others). The big advancements to Wapinski’s work are that they include a measure of gene order (synteny) and have constructed their framework to have the scalability and automation of hit clustering approaches (such as reciprocal best blast hits) without their obvious downfalls. Their Bioinformatics paper goes over the details of their algorithm and gives a brief overview of an initial application to 9 Ascomycota fungal genomes. They evaluate their algorithm’s robustness by bootstrapping and its accuracy by a both comparing to curated sets of orthologs and by using simulated data.

The follow-up Nature paper then extends this application to the complete set of 17 genomes of Ascomycota fungi. They define several class of evolutionary patterns: uniform orthogroups are those with no duplications or loss events; persistent orthogroups have at least one gene present in all species; and appearing orthogroups exist only within a subclade of the larger phylogeny. Ancestral orthogroups are present in the clade spanning Hemiascomycota and Euascomycota. They are able to show that groups with functional and/or interacting partners have coherent orthogroups and gene trees. This likely reflects co-evolutionary pressures.

Using a Poisson distribution they identified volatile orthogroups as those deviating significantly from random expectation and uniform orthogroups as those clearly within expectation. They then cross section the volatile and uniform groups with S. cerevisiae GO categories and expression data to ascertain that the uniform groups are enriched for essential growth functions, essential genes, and genes residing in organelles. The volatile genes, on the other hand, are those encoding transporters, receptors, cell wall proteins, and stress responders. This dichotomy is in line with the generally accepted wisdom that the evolutionary pressures on a gene will depend critically on function.

Finally, they add their weight to several recent reoccurring evolutionary conclusions:

  • Biochemical functions rarely diverge but regulation diverges readily
  • New modules do not form by duplicating existing one
  • Duplication modularizes networks by disentangling them (ie. duplicates specialize). [See: Lynch & Force (2000) Genetics 154:459-473.]

Admittedly I initially read the Nature paper and wondered what was the big deal here. Zmasek and Eddy (and others) presented a rigorous phylogenomic solution to the automation of orthology/parology ascertainment over 5 years ago. But on a second reading, I realize that my inital response was short sighted. Wapinski’s work has several advantages over earlier work. First, they incorporate gene order (synteny) into their resolution method. This is possible and advantageous given the large number of fully sequence genomes (which were largely unavailable when Zmasek’s work was published). Second, Wapinski’s pipeline is designed for whole genomes … it is therefore fast and scalable. Finally, Wapinski executed a rigorous and interesting analysis of the Ascomycota which utilized numerous types of data (sequence, synteny, GO categories, expression data) to clearly solidify many evolutionary principles of gene evolution. It will be interesting to see their methodology applied to the larger metazoan genomes.

Wapinski, I., Pfeffer, A., Friedman, N., Regev, A. (2007). Natural history and evolutionary principles of gene duplication in fungi. Nature, 449(7158), 54-61. DOI: 10.1038/nature06107


One Response to ““Natural History” of Ascomycota fungi”

  1. […] Robin reviews recent Nature paper by Ilan Wapinski et al describing the orthogroups. I’ve been remiss in reviewing the paper myself, but they’ve created an important resource in the SYNERGY tool for orthology identification and a database of orthologs of some ascomycete fungi. […]

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