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Evolutionary Analysis of Domain ArrangeMents (EVADAM); Evolutionäre Analyse von Domänenarrangements

Subject Area Bioinformatics and Theoretical Biology
Term from 2008 to 2013
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 69260766
 
Final Report Year 2015

Final Report Abstract

Protein evolution can, to a large extent, be described as the rearrangement of modules, typically structural domains. Many modules are versatile as they occur in many different combinations, or linear arrangements. Their sequence signatures, e.g. HMM profiles, are stored in databases such as PRODOM or Pfam. Proteins can thus not only be represented as strings of amino acids but also as strings of domain IDs (IDentifiers) taken from these data bases. Only recently it emerged that this representation is efficient and useful, for example for finding bio-medically important links or constructing phylogenies. This project is embedded in a larger effort as we also develop methods to investigate arrangements and their evolution by reconstructing their phylogenies, multiple alignments and visualisation tools. In a series of papers we have shown that: • Domains are frequently lost in a stochastic manner, i.e. at a fairly constant rate reminiscent of the molecular clock principle. • Novel domains arise rarely but if they arrive they are only fixed if they confer strong adaptive benefits and, consequently, are replicated within the lineage. • Therefore, novel domains and their radiation establish a third way to detect adaptation by comparative genome analysis and complements KaKs and family expansion/reduction. • Fusions and terminal losses dominate the creation of novel arrangements. • Rates on overall are very similar across several and very diverse clades. • The rates can – and will – be used to develop future methods for deep phylogeny reconstruction • These insights so far have been used and will continued to be used for genome analysis.

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