The origins and early evolution of DNA mismatch repair genes—multiple horizontal gene transfers and co-evolution

Abstract

To understand the evolutionary process of the DNA mismatch repair system, we conducted systematic phylogenetic analysis of its key components, the bacterial MutS and MutL genes and their eukaryotic homologs. Based on genome-wide homolog searches, we identified three new MutS subfamilies (MutS3-5) in addition to the previously studied MutS1 and MutS2 subfamilies. Detailed evolutionary analysis strongly suggests that frequent ancient horizontal gene transfer (HGT) occurred with both MutS and MutL genes from bacteria to eukaryotes and/or archaea. Our results further imply that the origins of mismatch repair system in eukaryotes and archaea are largely attributed to ancient HGT from bacteria instead of vertical evolution. Specifically, the eukaryotic MutS and MutL homologs likely originated from endosymbiotic ancestors of mitochondria or chloroplasts, indicating that not only archaea, but also bacteria are important sources of eukaryotic DNA metabolic genes. The archaeal MutS1 and MutL homologs were also acquired from bacteria simultaneously through HGT. Moreover, the distribution and evolution profiles of the MutS1 and MutL genes suggest that they have undergone long-term coevolution. Our work presents an overall portrait of the evolution of these important genes in DNA metabolism and also provides further understanding about the early evolution of cellular organisms.

Two new subfamilies of DNA mismatch repair proteins (MutS) specifically abundant in the marine environment

“…With over 1000 sequenced genomes from cells and over 1500 genomes from DNA viruses, the available sequence data now cover a wide spectrum of species, which have already helped advancing our understanding of the functions and evolution of protein families such as the MutS family (Eisen, 1998;Lin et al, 2007). However, given the huge diversity of girus genomes , they seem to be still underrepresented in this sequencing effort (Claverie et al, 2006;Claverie and Abergel, 2010); out of the 1500 available viral genomes, only a handful of genomes exceed 350 kb (for example, Mimivirus (1.2 Mb), CroV (730 kb), Emiliania huxleyi virus (407 kb), Paramecium bursaria Chlorella virus NY2A (369 kb), Marseillevirus (368 kb), Canarypox virus (360 kb)).…”

“…The selection of sequences was performed to maximize the coverage of diverse MutS subfamilies, referring to previous publications (Eisen, 1998;Lin et al, 2007), through iterative process involving clustering by BLASTCLUST (Altschul et al, 1997), inspection of sequence alignment and phylogenetic reconstruction. We used T-Coffee version 8.06 (Notredame et al, 2000) for multiple sequence alignment.…”

“…The MutS protein recruits the 'linker protein' MutL and together activates the endonuclease MutH, which nicks specifically the newly synthesized DNA strand to initiate DNA excision and resynthesis pathway. Homologs of E. coli MutS have been found in many species of bacteria, archaea and eukaryotes, and together classified in the MutS family (Eisen, 1998;Lin et al, 2007). In viruses, MutS homologs have only been found in Mimivirus, the closely related Mamavirus (La Scola et al, 2008;Yutin et al, 2009), and more recently in the giant marine virus, Cafeteria roenbergensis virus (CroV) with a 730-kb genome (Fischer et al, 2010).…”

“…With the accumulation of genome sequences and the following phylogenetic studies during the last decade, a significant advance has been made regarding the classification of diverse MutS proteins (Eisen, 1998;Lin et al, 2007). In this study, we use the following naming of the MutS subfamilies, which is adapted from the recent study by Lin et al (Lin et al, 2007).…”

“…In this study, we use the following naming of the MutS subfamilies, which is adapted from the recent study by Lin et al (Lin et al, 2007). In total, 12 subfamilies were previously described to compose the MutS family: 'MutS1/ MSH1' including E. coli MutS and the mitochondria-targeted fungal MutS homolog 1 (MSH1); 'MutS2', known to inhibit recombination in H. pylori (Pinto et al, 2005) and to possess a C-terminal endonuclease domain called the small MutS-related (Smr) domain (Moreira and Philippe, 1999;Fukui et al, 2008); 'MSH2', 'MSH3', 'MSH4', 'MSH5' and 'MSH6/7', found in most eukaryotes (with the exception of MSH7 being a plant-specific paralogous group of MSH6 (Wu et al, 2003)); another plantspecific MSH1 (called 'plt-MSH1' hereafter) with the GIY-YIG endonuclease domain at their C-terminus (Abdelnoor et al, 2006); 'MutS3', 'MutS4' and 'MutS5', recently described but functionally uncharacterized prokaryotic homologs (Lin et al, 2007), and the above mentioned 'MutS7' subfamily represented by the Mimivirus MutS homolog.…”