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First Comprehensive Analysis of Mosquito Y Chromosome Offers Clues for Vector Control

Monday, April 18, 2016

pnasA new PNAS paper offers the first detailed analysis of the Anopheles gambiae Y chromosome, which could prove critical for biological and infectious disease research. The report uncovered extensive remodeling of the Y chromosome, which consists almost entirely of highly repetitive sequence. The authors say this study “provides a long-awaited foundation for studying male mosquito biology, and will inform novel mosquito control strategies based on the manipulation of Y chromosomes.”

Radical remodeling of the Y chromosome in a recent radiation of malaria mosquitoes” comes from lead authors Andrew Brantley Hall, Philippos-Aris Papathanos, Atashi Sharma, and Changde Cheng, along with senior author Nora Besansky. This large collaboration combines scientific expertise from Virginia Polytechnic Institute and State University, the University of Notre Dame, NHGRI, Indiana University, and several other institutes. The project was formed to address the lack of information about the mosquito Y chromosome, which has hindered vector-control efforts. Previous sequencing initiatives had analyzed A. gambiae but reported only 180 kb of unordered sequence data for the Y chromosome; a related mosquito genome project revealed 57 short sequences, while some 200 kb of sequence data was generated from BAC clones for the chromosome.

The challenge lies in the highly repetitive sequences found in Y chromosomes across organisms. “The Y chromosome remains one of the most recalcitrant and poorly characterized portions of any genome more than a decade into the postgenomic era,” the authors write. Among mosquitoes, the Y chromosome is particularly interesting because males do not transmit disease, so shifting the sex ratio of populations is a promising vector-control approach for reducing the incidence of malaria, Zika virus, and other mosquito-borne disease.

The team used SMRT Sequencing to tackle the A. gambiae Y chromosome, first generating a 294 Mb de novo assembly followed by sequencing and completely assembling BAC clones. “We find that the A. gambiae Y consists almost entirely of a few massively amplified, tandemly arrayed repeats, some of which can recombine with similar repeats on the X chromosome,” the scientists report.

For further analysis, the scientists incorporated genome resequencing data from a recent species radiation and determined that the Y chromosome experiences rapid sequence turnover. They also used RNA-seq data to identify a small number of genes on the chromosome that had no homologs on the X chromosome. In addition, they found YG2, a conserved gene that may have a role in sex determination in the mosquito.

The authors note that SMRT Sequencing has been a game-changing development for analyzing Y chromosomes in many organisms, “promising a resource-efficient alternative” to the laborious processes used in the past. “Single-molecule sequencing reads were able to reveal complex repeat structures from whole-genome data and completely assemble heterochromatic BACs without manual finishing,” the scientists conclude. “These results suggest that continued single-molecule read length and throughput improvements may soon enable the complete reconstruction of Y chromosomes from whole-genome data alone.”

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