# The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of H2S in Drosophila melanogaster

## TL;DR

This study explores the effects of knocking out genes involved in hydrogen sulfide (H2S) synthesis in fruit flies, revealing impacts on lifespan, reproduction, and organ function.

## Contribution

The study identifies new biological pathways regulated by H2S-related genes in Drosophila, linking them to aging and disease.

## Key findings

- Double and triple knockout of H2S-related genes led to reduced lifespan and fecundity in Drosophila females.
- Transcriptomic analysis showed increased expression of genes related to excretion, detoxification, and reproduction in knockout strains.
- Single knockout of dtst1 increased fecundity and lifespan, contrasting with the effects of double and triple knockouts.

## Abstract

Here, we describe the effects of double knockout (KO) of the cbs and cse genes, which are responsible for H2S synthesis through the transsulfuration pathway, and KO of the sulfurtransferase gene (dtst1) in Drosophila melanogaster females. The analysis of H2S production in flies showed minimal levels in the double- and triple-knockout strains. The double- (cbs-/-; cse-/-) and triple- (cbs-/-; cse-/-; dtst-/-) KO flies exhibited a shortened lifespan and reduced fecundity, and showed dramatic changes in Malpighian tubule morphology. The transcriptomic analysis revealed a profound increase in the expression levels of several genes involved in excretory system function in the double-KO and especially the triple-KO flies. Importantly, major groups of differentially expressed genes (DEGs) in the whole bodies of females and ovaries of KO strains included genes responsible for detoxification, reproduction, mitochondrial activity, excretion, cell migration, and muscle system function. The reduced fecundity observed in the double- and triple-KO flies correlated with pronounced changes in the ovarian transcriptome. At the same time, the single knockout of dtst1 increased the flies’ fecundity and lifespan. Our experiments exploring unique Drosophila strains with KO of major H2S-related genes revealed several new pathways controlled by this ancient adaptogenic system that is involved in various human diseases and aging.