It has been suggested that humans may suffer a high genomic deleterious mut
ation rate(1,2). Here we test this hypothesis by applying a variant of a mo
lecular approach(3) to estimate the deleterious mutation rate in hominids f
rom the level of selective constraint in DNA sequences. Under conservative
assumptions, we estimate that an average of 4.2 amino-acid-altering mutatio
ns per diploid per generation have occurred in the human lineage since huma
ns separated from chimpanzees. Of these mutations, we estimate that at leas
t 38% have been eliminated by natural selection, indicating that there have
been more than 1.6 new deleterious mutations per diploid genome per genera
tion. Thus, the deleterious mutation rate specific to protein-coding sequen
ces alone is close to the upper limit tolerable by a species such as humans
that has a low reproductive rate(4), indicating that the effects of delete
rious mutations may have combined synergistically, Furthermore, the level o
f selective constraint in hominid protein-coding sequences is atypically lo
w, A large number of slightly deleterious mutations may therefore have beco
me fixed in hominid lineages.