No Evidence of Elevated Germline Mutation Accumulation Under Oxidative Stress in Caenorhabditis elegans

Abstract

Variation in rates of molecular evolution has been attributed to numerous, interrelated causes, including metabolic rate, body size, and generation time. Speculation concerning the influence of metabolic rate on rates of evolution often invokes the putative mutagenic effects of oxidative stress. To isolate the effects of oxidative stress on the germline from the effects of metabolic rate, generation time, and other factors, we allowed mutations to accumulate under relaxed selection for 125 generations in two strains of the nematode Caenorhabditis elegans, the canonical wild-type strain (N2) and a mutant strain with elevated steady-state oxidative stress (mev-1). Contrary to our expectation, the mutational decline in fitness did not differ between N2 and mev-1. This result suggests that the mutagenic effects of oxidative stress in C. elegans are minor relative to the effects of other types of mutations, such as errors during DNA replication. However, mev-1 MA lines did go extinct more frequently than wild-type lines; some possible explanations for the difference in extinction rate are discussed. Lanfear et al. 2007;and Galtier et al. 2009). Usually, it is supposed that organisms with high metabolic rates have higher rates of mutation, and thus faster rates of evolution, than do organisms with low metabolic rates. There are two (not mutually exclusive) ways by which metabolic rate might affect mutation rate. First, organisms with high metabolic rates have shorter generation times (Savage et al. 2004;Bromham 2009) and thus undergo relatively more rounds of DNA replication per generation (Laird et al. 1969;Ellegren 2007;Nikolaev et al. 2007;Thomas et al. 2010) than do organisms with low metabolic rates. If most mutations occur during DNA replication, a positive relationship between metabolic rate and mutation rate, and thus rates of evolution, is expected. Second, the oxygen-centered free radicals that are by-products of aerobic metabolism (Boveris and Chance 1973;Fridovich 2004) can cause oxidative damage to DNA (Hsie et al.

Drift-barrier hypothesis and mutation-rate evolution

“…One potential issue is that mutation-rate estimates are almost always obtained under optimal laboratory growth conditions, raising questions as to whether harsher environmental conditions would result in lower (or higher) levels of replication fidelity. Experimental work in this area has led to mixed results (31)(32)(33), and there is considerable room for further research.…”

Is metabolic rate a universal ‘pacemaker’ for biological processes?

“…Similarly, temperature effects on mutation rate may not be mediated by metabolic rate, but by other processes (e.g. In any case, the proposed mechanism by which metabolic rate may affect mutation rate, namely ROS production, appears to be absent in mammalian cells (Hoffmann et al, 2004) and the nematode Caenorhabditis elegans (Maupas) (Joyner-Matos et al, 2011). In addition, direct tests for associations between RMR and the rates of mutation or molecular evolution have usually produced nonsignificant results (Mooers & Harvey, 1994;Bromham, Rambaut & Harvey, 1996;Gissi et al, 2000;Lanfear et al, 2007;McGaughran & Holland, 2010;Feng et al, 2014).…”

Taller plants have lower rates of molecular evolution

“…Furthermore, although correlative evidence for the metabolic rate hypothesis in animals is mixed [24][25][26] , experiments in animals have shown that oxygen radicals generated in organelles do not damage the nuclear DNA of the same cell 27 , and that germ-line mutations do not accumulate under increased oxidative stress 28 . If the same is true for plants, the metabolic rate hypothesis cannot explain the link we have observed between height and rates of molecular evolution in the nuclear genome.…”