On the Organization of Higher Chromosomes

OHTA and Kimura¹ have argued that only about 6% of the sequences in mammalian DNA can be under the intense selection that has characterized the evolutionary history of the cytochromes c, the globin chains and the histones. From the calculated mutation rate of fibrinopeptides A and B they show that if all genes are subjected to the same mutation rate 8.3 mutations would accumulate per genome per generation. Because 0,5 deleterious mutations per genome per generation is the maximum allowable in an equilibrium population², they conclude that the amount of DNA that codes for informational sequences such as the cytochromes, globins and histones must be no more than 0.5/8.3, or 6%. We are therefore left with the interesting observation that 94% of mammalian nuclear DNA serves a function not under strong selection. These authors make several assumptions, one of which is that the spontaneous mutation rate characteristic of a species is constant over all nucleotide sequences. I suggest here that this assumption is incorrect, for a variety of reasons and that by assuming that spontaneous mutation rates vary sequence by sequence, one can arrive at a plausible organizing principle for the structure of higher chromosomes.