Resolution of several unsettled problems in genetics depends on the genomic
rate of deleterious mutation, U.Selection against mutations can be a major
factor in evolution only if U greater than or equal to1. Recently, signifi
cant progress has been made in measuring U in multicellular eukaryotes. An
indirect estimate, based on a human-chimpanzee pseudogene comparison, produ
ced U>3 for hominoids. By contrast, an estimate for Drosophila based on com
parison of synonymous protein-coding sites produced U<0.1. However, the Dro
sophila figure might be underestimated because of selection at synonymous s
ites. Perhaps,the best way to measure U is to observe mutations shortly aft
er they appear. So far, this direct approach has been applied only to human
s and Caenorhabditis elegans, yielding high estimates of mutation rates.