Evolution of resistance to natural gene drive systems – RESIST

Genomes can generally be viewed as cohesive units, in which most genes cooperate to increase organismal fitness, by making positive contributions to survival and reproduction of organisms. This cooperation largely arises because most genes are fairly transmitted from one generation to the next (e.g., diploid individuals transmit both alleles of a gene with equal likelihood). However, some genetic elements play by their own rules, biasing inheritance in their favour at the expense of the rest of the genome. By being overrepresented in an organism’s progeny, these selfish genetic elements can spread in a population over successive generations, even though they may be harmful to individuals. A plethora of such “drivers” have been reported in the literature and they are nearly ubiquitous in animals and plants. They can be located in the nucleus (e.g., meiotic drivers and transposable elements) or in the cytoplasm (e.g., selfish mitochondria and heritable symbionts) of cells. Appreciation of selfish genetic elements as an important source of evolutionary change and novelty has developed relatively recently. Over the past years, evidence has been accumulating on the role played by selfish genetic elements in shaping fundamental biological features and processes, such as genome structure, gene regulation, speciation, sex determination, development and immunity.

Drivers are sources of genetic conflicts because they increase their own transmission by being detrimental to other elements of the genome or to the organism. Variants of these other genetic elements are therefore selected if they mitigate the action of drivers. As a result, resistance traits that prevent driver over-transmission or effects are expected to evolve rapidly. In addition to their pervasive contribution to evolutionary innovation, genetic conflicts and resistance to drive are of prime relevance to the engineering of synthetic gene drive systems, which are currently being developed to control disease vectors and agricultural pests. Indeed, a crucial issue for these systems is the evolution of resistance, which may slow down or even prevent their spread and, hence, undermine their efficacy. However, our current understanding of the evolution and underlying mechanisms of resistance to drive is limited.

Sex ratio distorters are particularly well-suited for the study of resistance to drive. These selfish elements locate on sex chromosomes, or are transmitted by only one sex, and induce bias in sex ratios. This bias imposes strong selective pressure (known as sex ratio selection) favouring genotypes producing more individuals of the under-represented sex, and ultimately restoring Fisherian (balanced) sex ratios. Thus, genetic resistance is expected to rapidly evolve against sex ratio distorters.

Here we investigate the genetic basis, evolution and molecular mechanisms of drive and resistance in two emblematic sex ratio distorters: (i) the Paris Sex Ratio (SR) sex chromosome drive system of Drosophila simulans, and (ii) feminizing Wolbachia endosymbionts of the isopod Armadillidium nasatum. This is a collaboration between two major French laboratories working on selfish genetic elements, sex ratio distortion and resistance in arthropods: UMR 7267 Ecologie & Biologie des Interactions, CNRS/Université de Poitiers (Partner 1, renowned expert on the Wolbachia/isopod model) and UMR 9191 Evolution Génomes Comportement Ecologie, CNRS/Université Paris Saclay (Partner 2, renowned expert on the Drosophila SR system). Based on the high complementarity of our consortium and the use of a combination of cutting-edge evolutionary genomics and molecular biology methodologies, we will be able to draw broad conclusions on the biology of sex ratio distorters and the evolution of resistance to drive.