It is proposed that early in phylogeny a large proportion of amino acid substitutions were selectively neutral, but that bursts of adaptive substitutions during major radiations of life so increased selective constraints that most mutations in modern proteins are detrimental. Recent findings on D N A nucleotide sequences indicate that decreasing rnutation rates further slowed the rate of molecular evolution in the lineage to humans.
An Hypothesis on Neutral
Mutations and Slowing Rates Over twenty years ago the idea was put forward that molecular evolution slowed in the primate lineage which led to
Recent findings indicate that this is the case for amino acid replacements in proteins5, and for base substitutions in both noncoding and coding DNA7-l0 The original findings that suggested the hominoid slowdown idea were immunological. Almost no antigenic divergencies were found throughout the whole ape superfamily Hominoidea on comparing human (Homo), chimpanzee (Pan), gorilla (Gorilla), orangutan (Pongo), and gibbon (Hylobates) serum albumins, whereas marked albumin divergencies were evident within the ungulate family Bovidaeeven within the subfamily B~vinae.'-~ Moreover, for a range of serum proteins, humans showed only small antigenic differences from orangutans and gibbons and, at most, trace differences from gorillas and chimpanzees. Thus, considering the seemingly large amount of morphological evolution in the Hominoidea indicated by traditional taxonomic schemes that divide this superfamily into families Hominidae, Pongidae, and Hylobatidae, the amount of protein evolution distinguishing humans from other hominoids appeared to be surprisingly small.
An hypothesis was proposed', in which a slowdown of rates of protein evolution in the Hominoidea was the culmination of a long-term phylogenetic trend extending from the time of the origin of proteins to the present. This hypothesis, pre-dating the neutralist views of Kimura," postulated that early in phylogeny most amino acid replacements in proteins were selectively neutral. However, a small fraction of substitutions were adaptive and their accumulation over geological epochs, by shaping dense arrays of lock-and-key interaction sites on proteins, increased the number of selective constraints that cause most mutations in modern proteins to be detrimental. The slowdown in rates resulted from proteins having fewer sites where selectively neutral mutations could accumulate.