The Presence of the DNA Repair Genes mutM, mutY, mutL, and mutS is Related to Proteome Size in Bacterial Genomes

Abstract

DNA repair is expected to be a modulator of underlying mutation rates, however the major factors affecting the distribution of DNA repair pathways have not been determined. The Proteomic Constraint theory proposes that mutation rates are inversely proportional to the amount of heredity information contained in a genome, which is effectively the proteome. Thus, organisms with larger proteomes are expected to possess more efficient DNA repair. We show that an important factor influencing the presence or absence of four DNA repair genes mutM, mutY, mutL, and mutS is indeed the size of the bacterial proteome. This is true both of intracellular and other bacteria. In addition, the relationship of DNA repair to genome GC content was examined. In principle, if a DNA repair pathway is biased in the types of mutations it corrects, this may alter the genome GC content. The presence of the mismatch repair genes mutL and mutS was not correlated with genome GC content, consistent with their involvement in an unbiased DNA repair pathway. In contrast, the presence of the base excision repair genes mutM and mutY, whose products both correct GC → AT mutations, was positively correlated with genome GC content, consistent with their biased repair mechanism. Phylogenetic analysis however indicates that the relationship between the presence of mutM and mutY genes and genome GC content is not a simple one.

Rate and molecular spectrum of spontaneous mutations in the bacteriumEscherichia colias determined by whole-genome sequencing

“…This observation suggests that the G:C/A:T balance of the genomes of different organisms might be determined, at least in part, by the functioning of their MMR system. In a recent survey of 699 bacterial genomes, about 20% lacked one or more genes in the MMR pathway, but there was no correlation with the G:C content of the genomes (48). Two caveats apply to these results: (i) other repair activities in the cell may compensate for the absence of MMR; and (ii), the presence of the MMR genes does not mean that the system is functioning to the same extent in each organism.…”

hNAG-1 increases lifespan by regulating energy metabolism and insulin/IGF-1/mTOR signaling

“…The long-lived GH-resistant GH receptor (GHR)-KO mice which have high GH level, as well as Ames dwarf and Snell dwarf mice lacking GHexhibit dwarfism, increased subcutaneous adiposity, change in tissue sizes, and increased insulin sensitivity[1, 20]. Although hNAG-1 mice are significantly shorter in body length (Figure 2a) there are no significant differences in tissue sizes, length of femurs or organ weights (data not shown).…”

“…Previously, we have shown that hNAG-1 expression increases metabolic oxidation and thermogenesis in male mice which is responsible, in part, for the resistance of hNAG-1 mice to obesity [14]. Enhanced O 2 consumption and higher heat expenditure are consistent with increased oxidative metabolism and is associated with protection from HFD-induced obesity and enhanced longevity [1, 23]. In this study, heat production is slightly but statistically significant lower during the day in female line 1398 hNAG-1 mice (Figure 3a).…”

“…Aging is characterized by decline in cellular function and is associated with obesity, inflammation, altered energy metabolism, and insulin resistance [1, 2]. Understanding the mechanisms of aging with the goal of increased lifespan remains an area of intensive study.…”

“…The insulin/IGF-1 (IIS) signaling pathway is the most characterized metabolic pathway implicated in aging [2, 3]. Genetic suppression of IIS signaling extends longevity in worms, insects, and mammals [1]. Caloric restriction is the only efficient treatment known to increase mammalian lifespan other than genetic modifications [4].…”