Distinct mechanisms mediate X chromosome dosage compensation in Anopheles and Drosophila

Abstract

Sex chromosomes induce potentially deleterious gene expression imbalances that are frequently corrected by dosage compensation (DC). Three distinct molecular strategies to achieve DC have been previously described in nematodes, fruit flies, and mammals. Is this a consequence of distinct genomes, functional or ecological constraints, or random initial commitment to an evolutionary trajectory? Here, we study DC in the malaria mosquito Anopheles gambiae. The Anopheles and Drosophila X chromosomes evolved independently but share a high degree of homology. We find that Anopheles achieves DC by a mechanism distinct from the Drosophila MSL complex–histone H4 lysine 16 acetylation pathway. CRISPR knockout of Anopheles msl-2 leads to embryonic lethality in both sexes. Transcriptome analyses indicate that this phenotype is not a consequence of defective X chromosome DC. By immunofluorescence and ChIP, H4K16ac does not preferentially enrich on the male X. Instead, the mosquito MSL pathway regulates conserved developmental genes. We conclude that a novel mechanism confers X chromosome up-regulation in Anopheles. Our findings highlight the pluralism of gene-dosage buffering mechanisms even under similar genomic and functional constraints.

Gene-rich X chromosomes implicate intragenomic conflict in the evolution of bizarre genetic systems

“…S4 B ). In A. gambiae , element A is typically discussed as if fully X-linked, however, the X chromosome has been previously shown to be only partially composed of element A and parts of other Muller elements, while the rest of ancestrally Muller A genes are now found on autosomes ( 41 ), consistent with our results ( SI Appendix , Fig. S5 and Table S1 ).…”

Gene-rich X chromosomes implicate intragenomic conflict in the evolution of bizarre genetic systems

“…2a and Supp figure 4b). In Anopheles gambiae, element A is typically discussed as if fully X-linked, however the X chromosome has been previously shown to be only partially composed of element A and parts of other Muller elements, while the rest of ancestrally Muller A genes are now found on autosomes (41), consistent with our results (Fig. S5, Supplemental table 1).…”

Establishment and a comparative transcriptomic analysis of a male-specific cell line from the African malaria mosquito Anopheles gambiae

“…Assembly of the DC complex is male-specific, because in females, translation of MSL2, a key protein of the complex, is blocked by a female-specific protein SXL involved also in sex determination. A recent study demonstrated that the DC control in Anopheles is achieved by a completely different mechanism not employing MSL2 or H4K16ac 49 . The availability of the AgMM cell line may greatly facilitate identification and validation of the DC machinery components in Anopheles .…”