Knowing how introns originated should greatly enhance our understanding of the information we carry in our DNA. Gilbert’s suggestion that introns initially arose to facilitate recombination still stands, though not for the reason he gave. Reanney’s alternative, that evolution, from the early “RNA world” to today’s DNA-based world, would require the ability to detect and correct errors by recombination, now seems more likely. Consistent with this, introns are richer than exons in the potential to extrude the stem-loop structures needed for (...) the homology search that can lead to heteroduplex formation and the recognition of base mismatches. In nucleic acid sequences that were unable concomitantly to encode sufficient stem-loop potential, protein-encoding potential was constrained to arise as segments (exons) interrupted by segments rich in stem-loop potential (introns). Thus, sequences with properties that we now deem intronic are likely to have preceded the emergence of exons. (shrink)

Graphical AbstractMuller found halving gene dosage, as in males with one X chromosome, did not affect specific gene function. Why then was dosage “compensated?” This paradox was solved by invoking collective gene functions such as self/not self discrimination afforded by protein aggregation pressure. This predicts female susceptibility to autoimmune disease.

Sightings of the revolutionary comet that appeared in the skies of evolutionary biology in 1976—the selfish gene—date back to the 19th and early 20th centuries. It became generally recognized that genes were located on chromosomes and compete with each other in a manner consistent with the later appellation “selfish.” Chromosomes were seen as disruptable by the apparently random “cut and paste” process known as recombination. However, each gene was only a small part of its chromosome. On a statistical basis a (...) gene should escape disruption for many generations. This led George Williams and Richard Dawkins to a new definition of the gene, differing from conventional biochemical definitions in that there were no consistent genic boundaries. There had been no previous sightings of another revolutionary, albeit less verbally spectacular, comet that appeared in 1975—the homostability principle of Akiyoshi Wada. Each gene has a base composition “accent” that distinguishes it from its neighbors. We now see that recombination can be triggered by the shift in base composition at genic boundaries. Hence, the Williams-Dawkins definition approaches the conventional definitions. (shrink)

The function of meiotic recombination has remained controversial, despite recent inroads into mechanisms. Ideas concerning a possible role of recombination in the elimination or efficient incorporation of mutations have been backed by theoretical studies but have lacked empirical support. Recent investigations into the basis for local variations in recombination frequency in yeast have uncovered a strong association between recombination initiation sites and transcriptional regulatory sequences. Other recent studies indicate a strong correlation between transcription and mutation rates in yeast genes. Taken (...) together, these data imply that distributions of recombination and mutation frequencies may be strongly correlated. This suggests that recombination may be targeted to genomic sites of high mutation frequency; such a ‘mutation‐tracking’ function would clearly aid in the shuffling of mutations to break up unfavorable and create favorable allelic combinations. Moreover, recent insights into the mechanism of gene conversion in yeast reveal a very strong inherent bias in favor of alleles on the non‐initiating homolog. Combined with mutation tracking, these findings suggest a novel and general mechanism by which allelic gene conversion may act to eliminate mutations. (shrink)