The biological consequences of knockout of genes involved in the synthesis and metabolism of H2S in Drosophila melanogaster

Here, we describe the effect of knockout (KO) of two key genes (cbs, cse) responsible for H2S synthesis in the transsulfuration pathway as well as the inactivation of sulfurtransferase gene (dtst1) encoding single domain rhodanese on Drosophila melanogaster genome expression and several life-history traits. The analysis of H2S production in the KO flies showed its minimal level in the strain with double KO (CBS-/-; CSE-/-) while flies with triple KO (CBS-/-; CSE-/-; dTST1-/-) exhibited higher H2S level and improvements in lifespan. The transcriptomic analysis of fly bodies from the double KO strain with maximum disturbances of fitness components revealed a profound increase in the expression of genes involved in the functioning of the excretory system. Besides, double and triple KO flies exhibited drastic changes in Malpighian tubules' appearance. Inactivation of genes related to H2S metabolism resulted in altered expression of numerous loci involved in mitochondrial function. While KO of the dtst1 gene did not affect the genome expression, the triple KO flies exhibited more changes in the whole-body transcriptome than double KO flies. Reduced fecundity in double knockouts correlates with pronounced changes in ovarian transcriptome data. Surprisingly, the knockout of the dtst1 gene affected the flies' memory. Poly-A RNA-seq of ovaries and whole bodies of Drosophila melanogaster flies lacking crucial genes involved in sulfur metabolism