Sequence analysis allows functional annotation of tyrosine recombinases in prokaryotic genomes

Abstract

Background: Tyrosine recombinases perform site-specific genetic recombination in bacteria and archaea. They safeguard genome integrity by resolving chromosome multimers, as well as mobilize transposons, phages and integrons, driving dissemination of genetic traits and antibiotic resistance. Despite their abundance and genetic impact, tyrosine recombinase diversity and evolution has not been thoroughly characterized, which greatly hampers their functional classification.Results: Here, we conducted a comprehensive search and comparative analysis of diverse tyrosine recombinases from bacterial, archaeal and phage genomes. We characterized their major phylogenetic groups and show that recombinases of integrons and insertion sequences are closely related to the chromosomal Xer proteins, while integrases of integrative and conjugative elements (ICEs) and phages are more distant.We find that proteins in distinct phylogenetic groups share specific structural features and have characteristic taxonomic distribution. We further trace tyrosine recombinase evolution and propose that phage and ICE integrases originated by acquisition of an Nterminal arm-binding domain. Based on this phylogeny, we classify numerous known ICEs and predict new ones. Conclusions:This work provides a new resource for comparative analysis and functional annotation of tyrosine recombinases. We reconstitute protein evolution and show that adaptation for a role in gene transfer involved acquisition of a specific protein domain, which allows precise regulation of excision and integration. KEYWORDSTyrosine recombinases, integrative and conjugative elements, prokaryotes, evolution, phages BACKGROUND Tyrosine recombinases (TRs) form a large family of proteins that perform site-specific DNA recombination in a wide variety of biological processes [1,2]. They are involved in post-replicative segregation of plasmids and circular chromosomes in bacteria, archaea and phages, protecting genome integrity upon cell division. The highly conserved Xer proteins (e.g. XerC and XerD in E.coli) resolve chromosome multimers formed after DNA replication in prokaryotes (reviewed in [3]), and the Cre recombinase separates 3 dimers of the P1 phage genome (reviewed in [4]). Other TRs act as genetic switches, triggering phenotype variation within bacterial populations via DNA inversion or deletion [5-7]. In addition, TRs drive the mobilization of 'selfish' genetic elements, including various phages and transposons. Some mobile elements hijack host-encoded Xer proteins [8,9], while others encode distinct TRs to promote their own integration and transfer in bacterial genomes. Prominent examples of TR-carrying mobile elements are the integrative and conjugative elements (ICEs), also referred to as conjugative transposons. ICEs combine features of phages and plasmids, because they can both integrate into genomes and disseminate by conjugative transfer [10]. A large number of ICEs and related non-autonomous mobilizable elements are present in diverse bacterial taxa and provide effic...

SMART: recent updates, new developments and status in 2020

“…For this purpose, we bring together a comprehensive set of 68 domains that cover five major recombinase families namely transposase—DDE ( 8 ), relaxase—HUH ( 9 ), casposase—cas1 ( 10 ), (resolvase-) serine and (integrase-) tyrosine recombinase ( 11 ). Thirty-one models for DDE subfamilies, 10 for HUH and 1 for tyrosine recombinase were obtained from Pfam ( 12 ), a set of 20 tyrosine recombinases sub-families from ( 13 ) and six sub-families three belonging to serine, two to HUH and one to Cas1 were newly developed. Based on the association of most of the recombinase sub-families with specific mobile element types or cellular functions, these 68 domains together can be used as seeds for the identification and discrimination of diverse mobile element types namely transposable elements, phages, integrons, conjugative elements (plasmids and Integrative Conjugative Elements—ICE) and casposons.…”

Novel integrative elements and genomic plasticity in ocean ecosystems

“… a ) Maximum likelihood phylogeny of a comprehensive, representative set of Xer-like tyrosine recombinases from bacterial, archaeal and phage genomes as well as those identified in Prochlorococcus genomes in this study. Common types (grey) are labeled according to the classification introduced by Smyshlyaev et al 45 . Integrases found in phages, ICEs (integrative conjugative elements) or other mobile genetic elements (MGEs) and integrases associated with other functions are indicated by navy blue labels.…”

The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications?

“…The simple recombinases include a diversity of functions [157], including phase variation of pili by invertases and the acquisition of antibiotic resistance genes by class 1 integrons, and there are a small number of prophage that also utilize a simple recombinase, as identified for the Brujita Mycobacteriophage [158]. The second major group of tyrosine recombinases differ from the simple recombinases due to the presence of an N-terminal armbinding domain [155,159]. These arm-binding tyrosine recombinases are common to both bacteriophages and other mobile genetic elements such as genomic islands and ICEs [157,160].…”