Selfish genes, the phenotype, paradigm and genome evolution

Francis Crick and Leslie Orgel, Nature, 1980
Source | Archive.org

Francis Crick was a molecular biologist famous for discovering DNA. In 1980 he and chemist Leslie Orgel argued for large amounts of junk DNA based on selfish DNA, the C-value paradox, and because it just didn't seem to be used:

In summary, then, there is a large amount of evidence which suggests, but does not prove, that much DNA in higher organisms is little better than junk...

Although it is an old idea that much DNA in higher organisms has no specific function, and although it has been suggested before that this nonspecific DNA may rise to levels which are acceptable or even advantageous to an organism, depending on certain features of its life style, we feel that to regard much of this nonspecific DNA as selfish DNA is genuinely different from most earlier proposals... While proper care should be exercised both in labeling as selfish DNA every piece of DNA whose function is not immediately apparent and in invoking plausible but unproven hypotheses concerning the details of natural selection, the idea seems a useful one to bear in mind when exploring the complexities of the genomes of higher organisms. It could well make sense of many of the puzzles and paradoxes which have arisen over the last 10 or 15 years.

In the paper they also estimate a useless sequence of 1000 bases would have a selective disadvantage of 10^-6 and it would take 10⁶ to 10⁸ years for selection to remove it, while duplications arise and fix much more quickly. Moreso, some sequences (which they label selfish DNA) are predisposed to duplicate more often and selection favors them over sequences which are not. Therefore they predict large amounts of junk DNA.

They also argue that most DNA must be junk because so little of it codes for proteins:

the majority of DNA sequences in most higher organisms do not code for protein since they do not occur at all in messenger RNA. Nor is it very plausible that all this extra DNA is needed for gene control, although some portion of it surely must be.

As well as repeating the C-Value paradox:

There is a striking connection between DNA content per cell and the minimum generation time of the plant. In brief, if such an angiosperm has more than 10 pg of DNA per cell, it is unlikely to be an ephemeral (that is, a plant with a short generation time). If it is a diploid and has more than 30pg of DNA, it is highly likely to be an obligate perennial rather than an annual or ephemeral. The converse, however, is not true, there being a fair number of perennials with DNA content of less than 30pg and a few with less than 10pg. A clear picture emerges that if a herbaceous plant has too much DNA it cannot have a short generation time.... [in salamanders] species with the longer developmental times often have higher C values.... genome size sets a limit beyond which development cannot be accelerated...

We also have to account for the vast amount of DNA found in certain species, such as lilies and salamanders, which may amount to as much as 20 times that found in the human genome. It seems totally implausible that the number of radically different genes needed in a salamander is 20 times that in a man.