BMC Genomics BioMed Central 3BR2M0e0Cs2eG,eanrocmhicsarticle x Classification and evolutionary history of the single-strand annealing proteins, RecT, Redβ, ERF and RAD52 Lakshminarayan M Iyer, Eugene V Koonin and L Aravind* Address: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA E-mail: Lakshminarayan M Iyer - lakshmin@ncbi.nlm.nih.gov; Eugene V Koonin - koonin@ncbi.nlm.nih.gov; L Aravind* - aravind@ncbi.nlm.nih.gov *Corresponding author Published: 21 March 2002 BMC Genomics 2002, 3:8 This article is available from: http://www.biomedcentral.com/1471-2164/3/8 Received: 7 January 2002 Accepted: 21 March 2002 © 2002 Iyer et al; licensee BioMed Central Ltd. Verbatim copying and redistribution of this article are permitted in any medium for any purpose, provided this notice is preserved along with the article's original URL. Abstract Background: The DNA single-strand annealing proteins (SSAPs), such as RecT, Redβ, ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways. Recently, they have been shown to form similar helical quaternary superstructures. However, despite the functional similarities between these diverse SSAPs, their actual evolutionary affinities are poorly understood. Results: Using sensitive computational sequence analysis, we show that the RecT and Redβ proteins, along with several other bacterial proteins, form a distinct superfamily. The ERF and Rad52 families show no direct evolutionary relationship to these proteins and define novel superfamilies of their own. We identify several previously unknown members of each of these superfamilies and also report, for the first time, bacterial and viral homologs of Rad52. Additionally, we predict the presence of aberrant HhH modules in RAD52 that are likely to be involved in DNA- binding. Using the contextual information obtained from the analysis of gene neighborhoods, we provide evidence of the interaction of the bacterial members of each of these SSAP superfamilies with a similar set of DNA repair/recombination protein. These include different nucleases or Holliday junction resolvases, the ABC ATPase SbcC and the single-strand-binding protein. We also present evidence of independent assembly of some of the predicted operons encoding SSAPs and in situ displacement of functionally similar genes. Conclusions: There are three evolutionarily distinct superfamilies of SSAPs, namely the RecT/ Redβ, ERF, and RAD52, that have different sequence conservation patterns and predicted folds. All these SSAPs appear to be primarily of bacteriophage origin and have been acquired by numerous phylogenetically distant cellular genomes. They generally occur in predicted operons encoding one or more of a set of conserved DNA recombination proteins that appear to be the principal functional partners of the SSAPs. Introduction Homologous DNA recombination is a fundamental proc- ess in the biochemistry of DNA repair and replication, which contributes to the generation of the genetic diversi- ty critical for natural selection. An important step in the recombination process is the pairing of homologous dou- Page 1 of 11 (page number not for citation purposes)