Linus Pauling Institute

The distribution of functions within genomes of higher organisms relative to processes that lead to the spread of mutations in populations is examined in its general outlines. A number of points are enumerated that collectively put in question the concept of junk DNA: the plausible compatibility of DNA function with rapid substitution rates; the likelihood of superimposed functions along much of eukaryotic DNA; the potential for a merely conditional functionality in sequence repeats; the apparent adoption of macromolecular waste as a strategy for maintaining a function without selective grooming of individual sequence repeats that carry out the function; the likely requirement that any DNA sequence must be "polite" vis-'a-vis (compatible with) functional sequences in its genomic environment; the existence in germ-cell lineages of selective constraints that are not apparent in populations of individuals; and the fact that DNA techtonics - the appearance and disappearance of genomic DNA - are not incompatible with function. It is pointed out that the inverse correlation between functional constraints and rates of substitution cannot be claimed to be pillar of the neutral theory, because it is also predicted from a selectionist viewpoint. The dispensability of functional structures is brought into relation with the concept of reproductive sufficiency the survivability of genotypes in the absence of fitter alleles.