On causal roles and selected effects: our genome is mostly junk

Abstract

The idea that much of our genome is irrelevant to fitness-is not the product of positive natural selection at the organismal level-remains viable. Claims to the contrary, and specifically that the notion of "junk DNA" should be abandoned, are based on conflating meanings of the word "function". Recent estimates suggest that perhaps 90% of our DNA, though biochemically active, does not contribute to fitness in any sequence-dependent way, and possibly in no way at all. Comparisons to vertebrates with much larger and smaller genomes (the lungfish and the pufferfish) strongly align with such a conclusion, as they have done for the last half-century.

Fig. 1

Traits attributable to DNA. We include all effects of DNA that are detectable at some level other than that of the DNA itself (its sequence and amount): that is, all expressions in biochemical, physiological or behavioral phenotype and all measures of activity employed by ENCODE. Some will have a beneficial effect on organismal fitness in that their elimination would have a detrimental effect on survival and reproduction vis-à-vis the wild type, under environmental conditions encountered by the organism. Some will not. Of the former, only selected effect functions (adaptations) were positively selected in the past for their current contribution(s) to fitness, and are now presumably under purifying selection to maintain them. The products of CNE and exaptations are similarly presumed to be under purifying selection but the former were acquired without positive selection as in Fig. 2, while the latter may be the result of positive selection for some organismal function other than their current one, or at some level other than organismal (as in the rare TEs coopted into gene regulation), or result from genetic drift

Fig. 2

Constructive neutral evolution as illustrated by a simple toxin–antitoxin system. Shown are g (the antitoxin gene), h (the toxin gene) and p (a gene producing beneficial phenotype P). When both g and h products are present the phenotype P is expressed, since the g product suppresses (inhibits) the toxic effects of the h product. When g is deleted, h-product toxically inhibits expression of P, leading to the inference that g is essential for the function of P and may have undergone positive selection for the performance of P. But if g in fact were present before the h-product acquired its potential toxicity against P, and “pre-suppressed” such toxicity, no positive selection need be invoked. The suppression by chaperones of the effects of mutations in target proteins is an example of such CNE. In many other systems a simpler evolved dependence of one component “A” on another “B” permitted by the “pre-suppressive” activity of the second on possible, otherwise deleterious, mutations in the first can be imagined [38]. Again the conclusion that B evolved positively to support the activity of A would be unwarranted