ArticleMolecular biology and evolution2024
On the Origin and Evolution of the Mosquito Male-determining Factor Nix.
Article in Molecular biology and evolution, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 12 citations in OpenAlex.
- Self-limiting population suppression gene drive design in the West Nile vector mosquito, Culex quinquefasciatus.Nature communications · 2026Article
- Neoclassical development of genetic sexing strains for insect pest and disease vector control.Insect science · 2026Review
- Chromosome-scale genome assembly and developmental transcriptome of Aedes triseriatus, vector of La Crosse virus.BMC genomics · 2026Article
- Leveraging sex determination systems for genetic biocontrol of dipteran pests.Current opinion in insect science · 2026Review
- Mosquito sex determination: recent advances and applications.Current opinion in insect science · 2025Review
- Hybridization between Aedes aegypti and Aedes mascarensis mosquitoes leads to disruption of male sex determination.Communications biology · 2024Article
- The chromosome-scale genome assembly for the West Nile vector Culex quinquefasciatus uncovers patterns of genome evolution in mosquitoes.BMC biology · 2024Article
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
The mosquito family Culicidae is divided into 2 subfamilies named the Culicinae and Anophelinae. Nix, the dominant male-determining factor, has only been found in the culicines Aedes aegypti and Aedes albopictus, 2 important arboviral vectors that belong to the subgenus Stegomyia. Here we performed sex-specific whole-genome sequencing and RNAseq of divergent mosquito species and explored additional male-inclusive datasets to investigate the distribution of Nix. Except for the Culex genus, Nix homologs were found in all species surveyed from the Culicinae subfamily, including 12 additional species from 3 highly divergent tribes comprising 4 genera, suggesting Nix originated at least 133 to 165 million years ago (MYA). Heterologous expression of 1 of 3 divergent Nix open reading frames (ORFs) in Ae. aegypti resulted in partial masculinization of genetic females as evidenced by morphology and doublesex splicing. Phylogenetic analysis suggests Nix is related to femaleless (fle), a recently described intermediate sex-determining factor found exclusively in anopheline mosquitoes. Nix from all species has a conserved structure, including 3 RNA-recognition motifs (RRMs), as does fle. However, Nix has evolved at a much faster rate than fle. The RRM3 of both Nix and fle are distantly related to the single RRM of a widely distributed and conserved splicing factor transformer-2 (tra2). The RRM3-based phylogenetic analysis suggests this domain in Nix and fle may have evolved from tra2 or a tra2-related gene in a common ancestor of mosquitoes. Our results provide insights into the evolution of sex determination in mosquitoes and will inform broad applications of mosquito-control strategies based on manipulating sex ratios toward nonbiting males.
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