Continuing the discussion from Gauger: Alternate Reading Frames Unlike Human Design:
This is an excellent paper worth discussing further.
A strong characteristic observed in most viruses is an abundance of overlapping open reading frames (ORFs). Many of these ORFs lack a known function . Overlapping is a universal phenomenon, ubiquitous throughout the entire tree of life, including mammals , yet only in viruses it is present in a major scale . Gene overlapping originates from various mechanisms, most notably the use of alternative start codons, ribosomal read-throughs and frame shifts . The tendency for overlapping events is even higher in RNA viruses and in viruses with shorter genomes [29, 30].
Several studies have suggested various explanations for the abundance of overlapping genes (OGs) in viruses. One theory states that since viruses (especially RNA viruses) have a high mutation rate, overlapping events can increase their fitness in various ways . For example, OGs can act as a safety mechanism by amplifying the deleterious effect of mutations occurring within them, thus quickly eliminating such mutations from the viral population .
Another theory argues that overlapping has a role in gene regulation by providing an inherent mechanism for coordinated expression. In support of this theory is the presence of OGs that are functionally related or coupled by a regulatory circuit (e.g., a feedback loop) [28, 32].
A third theory describes overlapping as an effective mechanism for generating novel genes, by introducing a new reading frame on top of an existing one . According to this theory, pairs of OGs are usually composed of an old well-founded gene, and a novel gene that was overprinted on top of it [2, 33].
The most accepted theory argues for genome compression as the driving evolutionary force [1, 28, 34, 35]. Multiple arguments were raised to explain the need of viruses to have compact genomes: (i) The high mutation rate of viruses prevents them from having a long genome, as the likelihood of a deleterious mutation in each generation is length dependent . (ii) The advantage for infectivity of shorter genome that lead to faster replication. (iii) The physical size constraint imposed by the capsid’s volume . The physical size constraint is argued to be most dominant in icosahedral viruses due to the discrete nature of the T number, allowing only non-continuous changes in capsid size [34, 36]. Small viruses are also argued to be subject to an even greater evolutionary pressure towards compactness, hence their high abundance of overlapping .
The motivation for this study is to systematically assess the different theories that aim to explain long-term evolution.
Thanks for pointing to this article @Zachary_Ardern.