[1][2][5] The first proposals for the role CNE was in the evolutionary origins of complex macromolecular machines such as the spliceosome, RNA editing machinery, supernumerary ribosomal proteins, chaperones, and more.
[4][6][7] Since then and as an emerging trend of studies in molecular evolution,[8] CNE has been applied to broader features of biology and evolutionary history including some models of eukaryogenesis, the emergence of complex interdependence in microbial communities, and de novo formation of functional elements from non-functional transcripts of junk DNA.
[11] Many evolutionary biologists posit that CNE must be the null hypothesis when explaining the emergence of complex systems to avoid assuming that a trait arose for an adaptive benefit.
Therefore, the emergence of the A:B interaction "presuppresses" the deleterious nature of the mutation, making it a neutral change in the genome that is capable of spreading through the population via random genetic drift.
[13] In this case, the loss of B or the A:B interaction would have a negative effect on fitness and so purifying selection would eliminate individuals where this occurs.
This is explained relative to the original set of CNE models as follows:[1] In the gene-scrambling and RNA pan-editing cases, and in the fragmentation of introns, the initial state of the system (unscrambled, unedited, unfragmented) is unique or rare with regard to some extensive set of combinatorial possibilities (scrambled, edited, fragmented) that may be reached by mutation and (possibly neutral) fixation.
In the gene duplication model, as well as in the explanation for loss of self-splicing and for the origin of protein dependencies in splicing, it is assumed that mutations that reduce activity or affinity or stability are much more common than those with the opposite effect.
In the first scenario, the desired function may still be carried out because the two copies of the gene together (as opposed to having only one) can still produce sufficient product for the job.
This approach is simpler when analyzing complex traits of which evolved more recently and are taxonomically restricted in a few lineages because "derived features can be more easily compared to their sisters and inferred ancestors".
The large majority of organisms do not rely on RNA editing systems, and in the ones that do have it, the need for it is unclear as the optimal solution would be for the DNA sequence to not contain the wrong (or missing) nucleotides at several thousand sites to begin with.
However, a scenario where a primitive RNA editing system gratuitously arose prior to the introduction of errors into the genome is more parsimonious.
Once the RNA editing system arose, the original mitochondrial genome would be able to tolerate previously deleterious substitutions, deletions, and additions without an effect on fitness.
Once a sufficient number of these deleterious mutations took place, the organism would by this point have developed a dependency on the RNA editing system to faithfully correct any inaccurate sequences.
[11][20] Over the course of evolution, many microbial communities have emerged where individual species are not self-sufficient and require the mutualist presence of other microbes to generate crucial nutrients for them.
These dependent microbes have experienced "adaptive gene loss" in the face of being able to derive specific complex nutrients from their environment instead of having to synthesize it directly.
This highly dependent state of many microbes on other organisms is similar to how parasites undergo significant simplification when a large variety of their nutritional needs are available from their hosts.
[21] As a counterpart, W. Ford Doolittle and T. D. P. Brunet proposed the "Gray Queen Hypothesis" to explain the emergence of these communities with CNE.