This fine paper notes: 'The interplay between diverse functionalities could in principle result in DNA regions serving three or even more different needs.' Evidence is given that a 'DNA sequence bears signs of competing demands of 1) DNA function, 2) RNA function, and 3) protein function.' It is assumed that the latter demand is primary, so that nucleic level demands are secondary. However, the authors conclude that 'multiple demands on the DNA level coincide with a local decrease of protein structural constraints.' So 'in these dual- or multi-functional DNA regions the changes in the amino acid sequence of the encoded protein segments are restricted by the second functionality.' Thus, which should be considered “primary,” and which “secondary,” is an open question.

The theoretical basis of this extends back to at least 1971 [1]. The needs of proteins and their encoding nucleic acids are different, and there must be evolutionary trade-offs. Indeed, some proteins have acquired additional low complexity amino acid sequences that appear as mere place-holders, existing by default to serve the underlying needs of the encoding nucleic acids [2]. Apart from the pressure to encode a protein in genic regions, the various pressures on genomes include those on base composition (e.g. GC% and purine-loading), and on nucleic acid structure (e.g. stem-loop potential). The latter, like GC%, tends to be "genome-wide" and is not localized to genic sequences [3].

Usually the needs of nucleic acid function dominate. However, when genes are under strong positive selection pressure, or overlap other genes, DNA is forced to compromise. Stem-loop potential may be diverted to introns, which can then be more conserved than the neighboring exons [4].

1. Schaap T (1971) Dual information in DNA and the evolution of the genetic code. J Theor Biol 32:293-298.

2. Xue HY, Forsdyke DR (2003) Low complexity segments in "Plasmodium falciparum" proteins are primarily nucleic acid level adaptations. Mol Biochem Parasitol 128, 21-32.

3. Forsdyke DR (2011) Evolutionary Bioinformatics. New York: Springer.

4. Barrette IH, McKenna S, Taylor DR, Forsdyke DR (2001) Introns resolve the conflict between base order-dependent stem-loop potential and the encoding of RNA or protein: further evidence from overlapping genes. Gene 270: 181-189.