BODY SIZE, METABOLIC-RATE, GENERATION TIME, AND THE MOLECULAR CLOCK

There is increasing evidence for variation in rates of nucleotide subs titution among divergent taxonomic groups. Here, we summarize publishe d rate data and show a strong relationship between substitution rate a nd body size. For instance, rates of nuclear and mtDNA evolution are s low in whales, intermediate in primates, and fast in rodents. A simila r relationship exists for poikilothermic vertebrates. However, these t axa have slower mtDNA substitution rates overall than do homeotherms o f similar size. A number of physiological and life history variables a re highly correlated with body size. Of these, generation time and met abolic rate explain some patterns of rate heterogeneity equally well. In many cases, however, differences in metabolic rate explain importan t exceptions to the generation time model. Correlation between metabol ic rate and nucleotide substitution may be mediated by (i) the mutagen ic effects of oxygen radicals that are abundant by-products of aerobic respiration, and (ii) increased rates of DNA synthesis and nucleotide replacement in organisms with higher metabolic rates. Both of these f actors increase mutation rate by decreasing the ''nucleotide generatio n time,'' the average length of time before a nucleotide is copied eit her through replication or repair. Reconsideration of the generation t ime hypothesis to include physiological effects such as metabolic rate improves the theoretical underpinnings of molecular evolution.