Nucleotide sequence divergence and functional constraint in mRNA evolution.

Comparison of about 50 pairs of homologous nucleotide sequences for different genes revealed that the substitutions between synonymous codons occurred at much higher rates than did amino acid substitutions. Furthermore, five pairs of mRNA sequences for different genes were compared in species that had diverged at the same time. The evolutionary rate of synonymous substitution was estimated to be 5.1 X 10(-9) per site per year on the average and is approximately constant among different genes. It also is suggested that this property would be suitable for a molecular clock to determine the evolutionary relationships and branching order of duplicated genes. Each functional block of the noncoding region evolves with a rate that is almost constant, regardless of the types of genes. The intervening sequence and the 5' portion of the 3' noncoding region show considerable divergence, the extent of which is almost comparable to that in the synonymous codon sites, whereas the other blocks consisting of the 5' noncoding region and the 3' portion of the 3' noncoding region are strongly conserved, showing approximatley half of the divergence of the synonymous sites. This strong sequence preservation might be due to the functional requirements for transcription and modification of mRNA.