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.

Low dissolved O2, or hypoxia, is becoming increasingly prevalent in aquatic habitats and is considered to be stressful for aerobic organisms. However, hypoxia also can be beneficial by decreasing cellular stress, particularly that related to free radicals. Therefore, an animal’s ideal habitat may have the minimum O2 necessary to sustain aerobic metabolism, with excess O2 increasing the need to scavenge free radicals and repair free radical damage. Here we show that a natural population of small (<9 mm shell length) freshwater clams (genus Sphaerium Scopoli, 1777) lives along a dissolved O2 gradient from extreme hypoxia to moderate hypoxia. We tested the hypothesis that clams living in extreme hypoxia would have higher reproductive success than clams that live in moderate hypoxia. Clam abundance was highest in water with very low dissolved O2, conditions previously demonstrated to decrease cellular stress. The internally brooding clams reproduced year-round and had higher reproductive output in extreme hypoxia than in moderate hypoxia. The findings demonstrate that the apparent cellular-level benefits of hypoxia may translate into increased fitness, especially for small organisms.