Non-allelic gene conversion enables rapid evolutionary change at multiple regulatory sites encoded by transposable elements

Mutations change genes and provide the raw material for evolution. Genes are sections of DNA that contain the instructions for making proteins or other molecules, and so determine the physical characteristics of each organism. Genetic mutations that increase an organism's number of offspring and chances of survival are more likely to be passed on to future generations. Changes to when or where a gene is switched on (so-called regulatory mutations) can also provide fitness benefits and can therefore be selected for during evolution. Transposable elements are sequences of DNA that are also called ‘jumping genes’ because they can make copies of themselves and these copies of the transposable element can move to other locations in the genome. Some transposable elements contain sequences that switch on nearby genes. If different copies of a transposable element that contains such a regulatory sequence insert themselves in more than one place, it can result in a network of genes that can all be controlled in the same way. The regulatory sequences contained within transposable elements are not always optimal, but they can be fine-tuned through evolution. A fruit fly called Drosophila miranda has a transposable element called ISX that has, over time, placed up to 77 regulatory sequences around one of this species' sex chromosomes. Just as in humans, female flies are XX and males are XY; but having only one copy of the X chromosome means that male flies need to increase the expression of certain genes to produce a full-dose of the molecules made by the genes. This process is called dosage compensation and in 2013 the 77 ISX regulatory sequences on the fruit fly's X chromosome were shown to help recruit the molecular machinery that carries out dosage compensation to nearby genes, albeit inefficiently. Now Ellison and Bachtrog—who also conducted the 2013 study—report how these transposable elements have been fine-tuned to make them more effective for dosage compensation. Ellison and Bachtrog uncovered two mutations that make the ISX transposable element better at recruiting the dosage compensation molecular machinery. ISX spread around different locations along the fly's X chromosome before these mutations arose; this means that initially none of the 77 insertions carried the two mutations, but now 30% of the 77 elements have the mutations in all flies, and 41% have them in only some flies. The same mutations have spread between the different ISX elements because transposable elements with the mutations have been used to directly convert other ISX elements without them. These mutations have also become more common in the fruit fly population by being passed on to offspring and increasing their survival. These two routes have accelerated the fine-tuning of these transposable elements for use in gene regulation. This implies that regulatory sequences derived from transposable elements evolve in a way that is fundamentally different from those that arise by other means, as the direct conversion between these insertions allows fine-tuning mutations to spread more rapidly.