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Collaborative Effort Results in High-Quality Mosquito Genome, Raising Hope for Infectious Disease Control

Thursday, January 4, 2018

In an unprecedented crowd-sourced effort stoked by social media, 72 scientists collaborated via 25 conference calls and 3,323 emails to produce a new high-quality Aedes aegypti mosquito genome.

Aedes aegypti mosquitoAssembled using PacBio long-read sequencing, the resource could provide the DNA map researchers need to combat the pest and the infectious diseases it spreads, including Zika, dengue, chikungunya, and yellow fever.

Eager to share the results with the scientific community, lead author Leslie B. Vosshall, first author Benjamin Matthews, both of Rockefeller University, and colleagues at several other institutions, published a pre-print of their paper, “Improved Aedes aegypti mosquito reference genome assembly enables biological discovery and vector control” online at bioRxiv.

In it, they describe how they improved upon previous efforts which failed to produce contiguous sequences of the large (~1.3 Gb) and highly repetitive Ae. Aegypti genome. The most recent previous assembly, AaegL4, for instance, produced chromosome-length scaffolds but suffered from short contigs and more than 31,000 gaps.

Using SMRT Sequencing data, the team produced an assembly that is highly contiguous, representing a 93% decrease in the number of contigs. The PacBio contigs were scaffolded end-to-end to the three Ae. aegypti chromosomes using Hi-C technology, resulting in the new AaegL5 reference. They were able to validate local structure, predict structural variants between haplotypes, and generate a dramatically improved gene set annotation.

As co-author Jeffrey Powell, a mosquito researcher at Yale University, told the New York Times at the start of the Aedes Genome Working Group project: “If we’re going to control the creature, we need to know it frontwards and backwards.”

“Having a complete genome sequence of the beast will give us a fundamental understanding of its biology that you can’t get any other way,” he added.

The researchers have already used the new assembly to investigate several scientific questions that could not be addressed with the previous genome, a few of which include:

  • The structure of the elusive sex-determining “M” locus. Population suppressing strategies such as Sterile Insect Technique and Incompatible Insect Technique require that only males are released. A strategy that connects a gene for male determination to a gene drive construct has been proposed to effectively bias the population towards males over multiple generations, the authors note.
  • More complete accounting of insecticide-detoxifying glutathione-S-transferase genes. Could catalyze the search for new resistance-breaking insecticides.
  • The identity of multi-genes families that encode chemosensory receptors. A doubling in the known number of chemosensory receptors provides opportunities to link odorants on human skin to mosquito attraction, a key first step in the development of novel mosquito repellents.
  • The evolution of insecticide resistance and vector differences. Mapping new candidates for dengue vector competence could help devise geographically-specific strategies.

“We predict that AaegL5 will catalyze new biological insights and intervention strategies to fight the deadly arboviral vector,” the authors conclude. “The high-quality genome assembly and annotation described here will enable major advances in mosquito biology and has already allowed us to carry out a number of experiments that were previously impossible.”

 

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