Dosage compensation in Bombyx mori is achieved by partial repression of both Z chromosomes in males

Abstract

Interphase chromatin is organized precisely to facilitate accurate gene expression. The structure-function relationship of chromatin is epitomized in sex chromosome dosage compensation (DC), where sex-linked gene expression is balanced between males and females via sex-specific alterations to 3D chromosome structure. Studies in ZW-bearing species suggest that DC is absent or incomplete in most lineages except butterflies and moths, where male (ZZ) chZ expression is reduced by half to equal females (ZW). However, whether one chZ is inactivated (as in mammals) or both are partially repressed (as in C. elegans) is unknown. Using Oligopaints in the silkworm, Bombyx mori, we visualize autosome and chZ organization in somatic cells from both sexes for the first time. We find that B. mori interphase chromosomes are highly compact relative to Drosophila chromosomes. Importantly, we show that in B. mori males, both chZs are similar in size and shape and are more compact than autosomes or the female chZ after DC establishment, suggesting that both male chZs are partially and equally downregulated. We also find that in the early stages of DC, the female chZ repositions toward the nuclear center concomitant with increased Z-linked gene expression, revealing the first non-sequencing-based support for Ohnos hypothesis. These studies represent the first visualization of interphase genome organization and chZ structure in Lepidoptera. We uncover striking similarities between DC in B. mori and C. elegans, despite these lineages harboring evolutionarily distinct sex chromosomes (ZW/XY), suggesting convergent evolution of DC mechanisms and a possible role for holocentricity in DC evolution. SignificanceGenes on sex chromosomes (for example, the X chromosome in humans) are regulated by distinct processes that do not affect non-sex chromosomes (autosomes). The expression of genes of sex chromosomes needs to be balanced between males and females due to differences in sex chromosome dosage (XY versus XX). This sex-specific gene regulation is called dosage compensation (DC). In most species, DC is achieved by altering the shape and compaction of sex chromosomes specifically in one sex. In this study, we use a chromosome painting approach called Oligopaints to examine how DC is achieved in silkworms for the first time. This is the first study to visualize this phenomenon in a species with ZW sex chromosomes, which evolved completely independently of XY. We find evidence supporting a long-standing model for how DC mechanisms evolved across all organisms, and we show high similarity between DC in silkworms and nematodes, suggesting these mechanisms have emerged multiple independent times throughout evolution.