Natural and Engineered Sex Ratio Distortion in Insects

Abstract

Insects have evolved highly diverse genetic sex-determination mechanisms and a relatively balanced male to female sex ratio is generally expected. However, selection may shift the optimal sex ratio while meiotic drive and endosymbiont manipulation can result in sex ratio distortion (SRD). Recent advances in sex chromosome genomics and CRISPR/Cas9-mediated genome editing brought significant insights into the molecular regulators of sex determination in an increasing number of insects and provided new ways to engineer SRD. We review these advances and discuss both naturally occurring and engineered SRD in the context of the Anthropocene. We emphasize SRD-mediated biological control of insects to help improve One Health, sustain agriculture, and conserve endangered species.

Figure 1.

Simplified models of the sex-determination pathways in the vinegar fly Drosophila melanogaster (A) and the Mediterranean fruit fly Ceratitis capitata (B), and meiotic sex ratio distortion (C). A) In D. melanogaster, embryos that inherit two X chromosomes (depicted as red DNA molecules) express the primary signal Sex-lethal (SXL) which effects the female-specific splicing of the transformer (tra) transcript, leading to the production of a functional TRA protein (TRA^F). The TRA^F protein complex enables the female-specific splicing of the doublesex pre-mRNA, leading to the production of the female DSX protein isoform (DSX^F) which programs female differentiation (left). In contrast, embryos with a single X chromosome do not express a functional SXL, resulting in a truncated non-functional TRA (TRA^M) and subsequently the default male-specific splicing of dsx. This leads to the production of DSX^M, which programs male differentiation (right). The Y chromosome (depicted as a blue DNA molecule) does not directly participate in sex-determination. B) In C. capitata, a dominant male-determining factor, Maleness-on-the-Y (MoY) resides on the Y chromosome (in blue). Expression of MoY somehow induces male-specific splicing of the tra pre-mRNA, leading to the production of truncated and non-functional TRA proteins (TRA^M). The lack of a functional TRA results in male DSX^M isoform and male differentiation (left). Embryos that do not inherit the Y chromosome (or MoY) produce a functional TRA protein (TRA^F) complex by default, which leads to the production of DSX^F and female differentiation (right). See Meccariello et al. (2019) and Primo et al. (2020) for details and for the concept of an autoregulatory loop. C) Normal spermatogenesis of a heterogametic male with XY chromosomes will produce X- or Y-bearing sperms in equal proportion (left). In a hypothetical Y-linked X-shredder system (right), either natural or engineered, double-stranded DNA breaks along the X chromosome could lead to non-functional X-bearing sperms without affecting the Y chromosome-bearing sperms. As a result, sex ratio distortion will occur in the progeny of an affected heterogametic male (XY).