Lack of mismatch correction facilitates genome evolution in mycobacteria.
In silico genome sequence analyses suggested that mycobacteria are devoid of the highly conserved mutLS-based post-replicative mismatch repair system. Here, we present the first biological evidence for the lack of a classical mismatch repair function in mycobacteria. We found that frameshifts, but not general mutation rates are unusually high in Mycobacterium smegmatis. However, despite the absence of mismatch correction, M. smegmatis establishes a strong barrier to recombination between homeologous DNA sequences. We show that 10-12% of DNA sequence heterology restricts initiation of recombination but not extension of heteroduplex DNA intermediates. Together, the lack of mismatch correction and a high stringency of initiation of homologous recombination provide an adequate strategy for mycobacterial genome evolution, which occurs by gene duplication and divergent evolution.
Springer
Burkhard
B
Institut für Medizinische Mikrobiologie, Universität Zürich, Gloriastrasse 30/32, CH-3028 Zürich, Switzerland.
Sander
Peter
P
Sedlacek
Ludwig
L
Hardt
Wolf-Dietrich
WD
Mizrahi
Valerie
V
Schär
Primo
P
Böttger
Erik C
EC
D020137:Base Pair Mismatch; D001483:Base Sequence; D005075:Biological Evolution; D004260:DNA Repair; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D016368:Frameshift Mutation; D020440:Gene Duplication; D016678:Genome; D006801:Humans; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000235:genetics*; D011995:Recombination, Genetic; D012486:Salmonella typhimurium / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit