The evolution of genes: the chicken preproinsulin gene.

We have characterized a clone carrying a chicken preproinsulin gene, which is present in only one copy in the chicken genome. The gene contains two introns: a 3.5 kb intron interrupting the region encoding the connecting peptide and a 119 bp intron interrupting the DNA corresponding to the 5' non-coding region of the mRNA. This is similar to the structure of rat insulin gene II; therefore it represents the common ancestor. Since the rat insulin gene I lacks a 499 bp intron in the coding region, the rat genes have evolved by a recent gene duplication followed by loss of this intron in one copy. The divergences between insulin gene sequences, and also between globin genes, show that changes at introns and silent positions in coding regions appear very rapidly (7 X 10(-9) substitutions per nucleotide site per year), but that the accumulation of changes in these sites saturates, although not completely, after about 100 million years. From this we conclude that not all of these sites are neutral and that they do not behave as accurate evolutionary clocks over long periods of time. However, nucleotide substitutions leading to amino acid replacements are an excellent clock. Our analysis indicates that this clock is driven by selection.