XI.6.2.3 The fact that the number of nucleotides in a repetitive motif cannot usually be divided by three facilitates protein structure reconstruction after a frame-shift mutation
Susumo Ohno, who carried out the most research on the internal periodicity of gene sequences, pointed out the fact that, although there are usually various numbers of nucleotides in repetitive oligonucleotides, multiples of three are not frequently encountered (Ohno 1985).If we admit that the sequences were formed under conditions when the triplet code already existed, then this property of genes can be considered to be a defense against drastic changes in the structure of proteins that would otherwise occur through the influence of frameshift mutations.If, for example, a gene is constructed as a tandem repetition of the octanucleotide AATGCCAT,
AATGCCAT AATGCCAT AATGCCAT AATGCCAT...,
and nucleotide A is inserted in position 2, the sequence of triplets changes from the sequence
AAT GCC ATA ATG CCA TAA TGC CAT AAT GCC ATA...
to the sequence
AAA TGC CAT AAT GCC ATA ATG CCA TAA TGC CAT...
It is apparent that the new sequence of triplets corresponds to the old sequence of triplets beginning with the fourth triplet.If the number of nucleotides in one repetition were divisible by three, the original sequence of triplets would never be renewed.
The possibility of renewal of the original sequence is not in contradiction with what was said in the previous section dealing with the formation of new proteins by a reading-frame shift.In present-day genes, most of the original periodicity has been almost eliminated as a consequence of accumulation of a great many mutations.Thus, following a frameshift mutation, the original sequence of aminoacids in the protein will certainly not be renewed.However, the periodicity could have been much greater in the initial stages of evolution.Because of the expected greater frequency of occurrence of frameshift mutations in this period of biological evolution and because of the lower precision of replication and proteosynthesis, the role of a process capable of ensuring greater resistance of the system to frameshift mutations could have been substantially greater at that time.