Friday, February 16, 2007

Antisense and evolution

Since I'm digging up old Kenster stories I thought I should mention this one...While the switch from the RNA world to the DNA->RNA->protein world remains a mystery there is no shortage of opinion on how that transition might have happened. One of such theories states that there is actually a structural link between RNA sequence and protein sequence. So for example if you were to take the receptor RNA and take the antisense strand of that receptor, it would generate a peptide that would be sticky to the receptor, however it has long been debunked: "We followed an approach which predicts that translation of two complementary RNA strands into protein generates pairs of "antisense" peptides which bind each other with specific and high affinity (Bost et al. Proc. Natl. Acad. Sci. (1985) 82, 1372). We used human parathormone as an experimental example, and we analysed by computer homologies between antisense peptide sequences and their published receptor sequences. We conclude that there is no experimental indication that parathormone binds to a synthetic peptide, the sequence of which was derived from the antisense RNA sequence. Based on homology scores and antigenicity indexes (Hopp) the analysis shows that the peptide ligand itself, or a random artificial peptide, are as good candidates as the antisense peptide in producing antibodies, presumably recognizing the receptor. We therefore question the general applicability of this approach"

Some people also beleive that the antisense strand has the capacity of encoding functional peptides and may be important during evolution for the formation of new genes when there is an inversion: "The question whether the noncoding DNA strand had or still has the capability for encoding functional polypeptides has been addressed in several articles. The theoretical background of the views advocating this idea arose from two groups of findings. One of them was based on various observations implying that the genetic code was adapted for double-strand coding. The other group of theories arose from the observation of gene-length overlapping open reading frames (O-ORFs) on the antisense DNA strand in a number of genes. In fact, the above theories, which I term selectionist, conceive a novel conception of gene evolution, proposing that new genes can be created by the utilization of antisense DNA strand. In contrast, neutralist theory claims that the O-ORFs are mere by-products of evolutionary processes acting to create special codon usage and base distribution patterns in the coding sequences"