RAPID DECLINE IN FITNESS OF MUTATION ACCUMULATION LINES OF GONOCHORISTIC (OUTCROSSING) CAENORHABDITIS NEMATODES

Evolutionary theory predicts that the strength of natural selection to reduce the mutation rate should be stronger in self‐fertilizing than in outcrossing taxa. However, the relative efficacy of selection on mutation rate relative to the many other factors influencing the evolution of any species is poorly understood. To address this question, we allowed mutations to accumulate for ∼100 generations in several sets of “mutation accumulation” (MA) lines in three species of gonochoristic (dieocious) Caenorhabditis (C. remanei, C. brenneri, C. sp. 5) as well as in a dioecious strain of the historically self‐fertile hermaprohodite C. elegans. In every case, the rate of mutational decay is substantially greater in the gonochoristic taxa than in C. elegans (∼4× greater on average). Residual heterozygosity in the ancestral controls of these MA lines introduces some complications in interpreting the results, but circumstantial evidence suggests the results are not primarily due to inbreeding depression resulting from residual segregating variation. The results suggest that natural selection operates to optimize the mutation rate in Caenorhabditis and that the strength (or efficiency) of selection differs consistently on the basis of mating system, as predicted by theory. However, context‐dependent environmental and/or synergistic epistasis could also explain the results.     

How long should angiotensin-converting enzyme inhibitors be given to patients following myocardial infarction: implications of the HOPE trial

Long-term treatment with angiotensin-converting enzyme inhibitors reduces post-infarction morbidity and mortality in patients with left ventricular (LV) systolic dysfunction or symptomatic heart failure. Until recently, the effect of such treatment in patients with preserved LV function has not been known. The results from the Heart Outcome Prevention Evaluation trial have indicated that long-term treatment with ramipril leads to a significant reduction in cardiovascular events in patients with atherosclerotic disease, including those with prior myocardial infarction and preserved LV function. These results suggest that long-term angiotensin-converting enzyme inhibition should also be considered in post-infarction patients with normal cardiac function.