Hamming’s first class research

PLoS Computational Biology has a regular series on “Ten Simple Rules”. Last week the series stole their ten simple rules from Richard Hamming’s 1986 Bell Communications Research Colloquium Seminar transcript. The PLoS editorial brings attention to this wonderful transcript which should be read by everyone.

Orthologous TFs have different functions and regulate different genes.

A recent PLoS Comp. Bio paper by Price, Dehal and Arkin (2007) looked at the evolution of transcription factors — focusing on the ability of bi-directional blast hits (BBH) to predict orthology. Their findings (in brief):

1. BBHs of TFs from distantly related bacteria are usually not evolutionary orthologs.
2. False orthologs typically respond to different signals and regulate different genes.
3. True evolutionary orthologs typically have (nearly) conserved function.
4. Regulatory networks evolve more rapidly than previously thought, as even closely in closely related species specific predictions are incorrect.

Anyone who has followed the literature on gene duplication evolution, the orthology inference problem, or TF binding/motif evolution should not be surprised by their findings. Predicting the associations of a particular TF with targets might not even be inferrable in detail (even in closely related sequences) if the “neutral binding” / “neutral turnover” model is true.

M. Eisen’s work in the twelve Drosophilia species emphasizes this point as well — since the two points he raised at the recent RECOMB meeting on Regulatory Genomics were that (1) most binding may be neutral and (2) distant enhancers with very different patterns of binding events can still drive correct patterning in Drosophilia. I am reminded of G. Wray who stated (in his Jan 2005 Symposium on Complex Life Histories in Marine Bathic Invertebrates) that the “picture of cis-regulatory sequence evolution that is emerging is one of dynamic change at the level of sequence comparison, coupled with long-term conservation of expression profiles.”

Price, M.N., Dehal, P.S., Arkin, A.P. (2007). Orthologous Transcription Factors in Bacteria Have Different Functions and Regulate Different Genes. PLoS Computational Biology, 3(9), e175. DOI: 10.1371/journal.pcbi.0030175

Evolutionary Dynamics of Language

A pair of letters appeared in this week’s Nature which are quite interesting. Pagel et. al. have a piece on how the frequency of word-use predicts the rate of lexical change in Indo-European history [Nature 449:717-721]. This is complemented by the Lieberman et. al. piece on quantifying the evolutionary dynamics of language [Nature 449:713-716], which focuses in on the use of conjugation. There is also a corresponding News and Views written by W. Tecumseh Fitch which puts these two papers into the context of the larger field of linguistics.

Modeling Gene Regulatory Networks

Goutsias and Lee have a paper in Curr. Pharma Design (2007) 13:1415-1436 which is an interesting mix of a review with some new results. I’ll focus here on their review of computational and experimental approaches, as I think they do a pretty good job of categorizing approaches to the network modeling problem. Their “gets us grants” application is to try to tackle colon cancer as the system of interest … but I refer you to their paper for those details.