Researchers Use New Technology to Sequence Mosquito Sex Chromosome

    The genome of the malaria-carrying mosquito was sequenced at least a decade ago, and current mosquito-control efforts emphasize genetic strategies for biasing mosquito populations toward males, particularly infertile males. So, you would think that we would have figured out the mosquito’s Y chromosome. But we hadn’t—at least not until the recently announced success of a Y chromosome–sequencing project.  

    The project, which involved a large international consortium, was described in an article that appeared March 29 in the Proceedings of the National Academy of Sciences (PNAS). The article explains how scientists overcame difficulties in sequencing the Y chromosome, which previously stumped the algorithms used by computers to assemble the mosquito’s entire genetic makeup. Also, the article explains how scientists discovered a long-hypothesized male-determining gene in the Anopheles mosquito species that carries malaria, laying the groundwork for the development of strategies that could help control the disease, which kills as many as 907,000 people each year.  

    A team of researchers with the Fralin Life Science Institute at Virginia Tech, working with a large international consortium, has sequenced the Y chromosome—the genetic driver of sex-determination and male fertility—in a family of malaria spreading mosquitoes.  

    “We were able to get around this obstacle (at least partially) by using a new long single-molecule sequencing technology, a new bioinformatics algorithm specifically designed to identify Y sequences, and physical mapping of DNA directly to the Y chromosome,” said co-author Igor Sharakhov, an associate professor of entomology at Virginia Tech. “Our study provides a long-awaited foundation for studying mosquito Y chromosome biology and evolution.”  

    “Our combined efforts have resulted in the most extensive characterization of the Y chromosome to date in additional malaria vectors as well, which will help identify targeted vector control approaches for different species,” said co-author Atashi Sharma, a doctoral at Virginia Tech.  

    The release issued by the University of California Riverside noted that the scientists participating in the project found only one gene, known as YG2, which is exclusive to the Y chromosome across the species complex, and thus is a possible male-determining gene.  

    “Exploiting 52 sex-specific An. gambiae RNA-Seq datasets representing all developmental stages, we identified a small repertoire of Y-linked genes that lack X gametologs and are not Y-linked in any other species except An. gambiae, with the notable exception of YG2, a candidate male-determining gene,” the authors of the PNAS paper wrote. “YG2 is the only gene conserved and exclusive to the Y in all species examined, yet sequence similarity to YG2 is not detectable in the genome of a more distant mosquito relative, suggesting rapid evolution of Y chromosome genes in this highly dynamic genus of malaria vectors.”  

    The paper also noted that interest in male mosquitoes has been motivated by the potential to develop novel vector control strategies, exploiting the fact that males do not feed on blood or transmit diseases, such as malaria. “The extensive characterization of the An. gambiae Y provides a long-awaited foundation for studying male mosquito biology,” the paper concluded, “and will inform novel mosquito control strategies based on the manipulation of Y chromosomes.”