Guy1, a Y-linked embryonic signal, regulates dosage compensation in Anopheles stephensi by increasing X gene expression

Abstract

We previously showed that Guy1, a primary signal expressed from the Y chromosome, is a strong candidate for a male-determining factor that confers female-specific lethality in Anopheles stephensi (Criscione et al., 2016). Here, we present evidence that Guy1 increases X gene expression in Guy1-transgenic females from two independent lines, providing a mechanism underlying the Guy1-conferred female lethality. The median level gene expression (MGE) of X-linked genes is significantly higher than autosomal genes in Guy1-transgenic females while there is no significant difference in MGE between X and autosomal genes in wild-type females. Furthermore, Guy1 significantly upregulates at least 40% of the 996 genes across the X chromosome in transgenic females. Guy1-conferred female-specific lethality is remarkably stable and completely penetrant. These findings indicate that Guy1 regulates dosage compensation in An. stephensi and components of dosage compensation may be explored to develop novel strategies to control mosquito-borne diseases.

femaleless Controls Sex Determination and Dosage Compensation Pathways in Females of Anopheles Mosquitoes

“… 21 , 49 Similarly, in A. stephensi , the X chromosome dosage in males is regulated by the Y linked maleness gene guy-1 . 50 Female-specific lethality observed in this study suggests that dosage compensation is activated in Anopheles females in response to depletion of fle transcripts. To evaluate whether misregulation of the X chromosome transcription is indeed involved, we compared transcriptomes of female pupae from a wild-type line and from the 4M4B transgenic line, in which female lethal effects occur during late stages of development.…”

Hidden genomic features of an invasive malaria vector, Anopheles stephensi, revealed by a chromosome-level genome assembly

“…Even though the Y chromosome plays an important role in male biology and sexual conflicts, its highly repetitive nature poses steep challenges for assembly and molecular characterization of the Y chromosome in Anopheles [7,8,18,28,40,58]. Due to the improved Y representation in our assembly, we characterized the repeat and gene content that previously evaded scrutiny.…”

Conditional knockdown of transformer in sheep blow fly suggests a role in repression of dosage compensation and potential for population suppression

“…In wild type males, the Y-linked sex determining gene Yob [41] is thought to somehow inactivate fle and thus promote dosage compensation [34,42]. In the related mosquito A. stephensi, expression of the Y-linked gene Guy1 in transgenic lines was lethal to females, which appears to be due to a significant increase in expression of X-linked genes compared to autosomal genes [43]. Guy1 is strong candidate for the male determining factor [44] and may also somehow inactivate fle as knockdown of fle expression in A. stephensi embryos caused female-specific lethality [34].…”

“…In the related mosquito A . stephensi , expression of the Y-linked gene Guy1 in transgenic lines was lethal to females, which appears to be due to a significant increase in expression of X-linked genes compared to autosomal genes [ 43 ]. Guy1 is strong candidate for the male determining factor [ 44 ] and may also somehow inactivate fle as knockdown of fle expression in A .…”