Decision letter: Har-P, a short P-element variant, weaponizes P-transposase to severely impair Drosophila development

Abstract

DNA provides the instructions needed for life, a role that relies on it being a very stable and organized molecule. However, some sections of DNA are able to move from one place in the genome to another. When these “mobile genetic elements” move they may disrupt other genes and cause disease. For example, a mobile section of DNA known as the P-element causes a condition called gonadal dysgenesis in female fruit flies, leading to infertility. Only certain strains of fruit flies carry P-elements and the severity of gonadal dysgenesis in their daughters varies. For example, when male fruit flies of a strain known as Harwich (or Har for short) is crossed with female fruit flies that do not contain P-elements, all of their daughters develop severe gonadal dysgenesis and are infertile. However, if the cross is done the other way around, and female Har flies mate with males that do not contain P-elements, the daughters are fertile because the Har mothers provide their daughters with protective molecules that silence the P-elements. But it was a mystery as to why the P-elements from the Har fathers always caused such severe gonadal dysgenesis in all the daughters. Here, Srivastav et al. bred fruit flies to create offspring that had different pieces of Har DNA in a genetic background that was normally free from P-elements; they then analyzed the ‘hybrid’ offspring to identify which pieces of the Har genome caused gonadal dysgenesis in the daughter flies. These experiments showed that Har flies possess a very short variant of the P-element (named “Har-P”) that is more mobile than other variants. However, the Har-P variants still depended on an enzyme known as P-transposase encoded by the full-length P-elements to move around the genome. Further experiments showed that other strains of fruit flies that cause severe gonadal dysgenesis also had very short P-element variants that were almost identical to Har-P. These findings may explain why Har and some other strains of fruit flies drive severe gonadal dysgenesis. In the future, it may be possible to transfer P-transposase and Har-P into mosquitoes, ticks and other biting insects to make them infertile and help reduce the spread of certain diseases in humans.