As you all know, Francis Crick was a co-author of the Nobel Prize-winning work on the structure of the DNA molecule, which was first published in 1953. He also played a major role in the subsequent deciphering of the genetic code (with a key study published in 1961), among other important contributions made throughout his career. Notably, he co-authored one of the highly influential “selfish DNA” papers in 1980, which is so often cited as an example of non-genic DNA being dismissed as useless. As I have noted elsewhere, Crick did not dismiss non-coding DNA as useless junk in that paper, but that hasn’t stopped people from (mis-)citing it as such.
In June 1959, two years before publishing the classic Crick, Brenner, et al. experiment (1961) and three years before he was awarded the Nobel Prize (1962), Crick took part in a symposium entitled “Structure and Function of Genetic Elements” at the Brookhaven National Laboratory. His contribution was entitled “The present position of the coding problem”. One of the unexplained observations that he outlined at the time involved a disparity in the base composition (the relative abundance of A, C, G, and T) among species. As he wrote:
“This large variation of DNA composition is very unexpected. The abundance of the various amino acids does not, as far as we know, vary much from organism to organism; leucine is always common, methionine usually rather rare. The small variation of RNA composition is exactly what might be expected; the large variation reported for DNA needs some special explanation”.
In other words, although the amino acids and their relative abundances are quite similar across different species, the DNA in their genomes as a whole differs markedly in base composition. If the genetic code is universal — i.e., the same codons specify the same amino acids across species — then why would base composition be so divergent among taxa?
Crick went on to list six possible explanations, though as he put it, “in my view they all, at the moment, appear unattractive”. The first one is particularly informative with regard to the myth that geneticists remained stubbornly closed-minded about the possibility of function in non-coding DNA until rather recently.
Here is what Crick (1959) said about the possibility that “only part of the DNA codes protein” (emphasis added):
“[Under this possible explanation] it is postulated that the sequences of bases in a DNA molecule are of two types: one makes ‘sense,’ that is, codes an amino acid sequence; the other makes ‘nonsense,’ that is, has some other function. The difficulty of this idea is that the nonsense must make up a rather large fraction of the DNA. If, for example, it is assumed that the base composition of he sense is reflected in that of the total RNA of the organism, then organisms showing extreme base ratios must have a minimum of 35% nonsense in their DNA.
If nonsense exists it can be asked how, in one molecule of DNA, the sense and nonsense are interdispersed. Are they coarsely or finely dispersed? As an example of the former, consider what might happen if dud genes could not be eliminated by genetic deletion. The base composition of such genes might well drift to extreme values because of mutagenic bias within the cell. This explanation is not very likely, and in addition demands that dud genes be reasonable uniformly distributed among DNA molecules.
A possible reason for the fine dispersion of nonsense might be the provision of ‘commas’. For example, these might take the form of segments that could pair by twisting back on themselves when the two chains of the DNA were separated. The base pairs of these regions could vary without altering their function. Alternatively a short sequence of bases, different from species to species but always the same in any one species, might act as a comma.”
Part of the Quotes of interest series.