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Team Sequences Mosquito Genomes to Better Understand Malaria Parasite Transmission

Anopholes stephensi

NEW YORK (GenomeWeb) – An international team has sequenced the genomes of mosquitoes from more than a dozen global Anopheles species in search of genetic features that explain differences in the insects' ability to transmit malaria-causing Plasmodium parasites.

As they reported online recently in Science, researchers from Notre Dame, the Broad Institute, and elsewhere did genome and transcriptome sequencing on 16 Anopheles species from sites in Africa, Asia, Europe, and South/Central America.

Compared to the fruit fly genome, the mosquito sequences seemed to lose and gain genes quite quickly, the team reported. They also tended to show rearrangements affecting the X chromosome and the loss of intronic sequences separating protein-coding portions of genes.

Still, the study's authors saw that "[s]ome determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover, but instead diversity through protein-sequence changes."

"This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts," they noted.

Although hundreds of Anopheles species have been described, only a few dozen are known for transmitting Plasmodium species that cause malaria in humans, the researchers noted, prompting interest in understanding the interplay between parasite, mosquito, and human adaptations.

"Human malaria is transmitted only by mosquitoes in the genus Anopheles, but not all species within the genus, or even all members of each vector species, are efficient malaria vectors," they explained. "This suggests an underlying genetic/genomic plasticity that results in variation of key traits determining vectorial capacity within the genus."

In their effort to untangle some of the genetic features that influence mosquitoes' ability to act as Plasmodium parasite vectors, the investigators used Illumina instruments to sequence pooled genomic DNA and pooled RNA samples from mashed mosquito bodies representing wild or lab strains from 16 Anopheles species.

The species selected diverged from one another as far back as around 100 million years ago, the team noted, and varied in their range, preferred blood meal sources, and so on.

With the help of the transcriptome sequence data, the researchers annotated genomes for each species, which contained 10,738 to 16,149 predicted protein-coding sequences apiece. These collections included both species-specific genes and genes shared with other organisms in the mosquito and/or insect lineages.

The mosquito genomes were marked by particularly high rates of X chromosome rearrangements, which were roughly 2.7 times more common than rearrangements occurring on autosomal mosquito chromosomes.

The team's comparison between mosquito and Drosophila sequences also indicated that genes from the mosquito X chromosome are more prone to move to other chromosomes over time than they are in the fruit fly.

Similarly, gene losses, gene gains, gene fissions, and gene fusions appeared relatively common in mosquito genomes compared to a dozen Drosophila genomes considered for the study, researchers reported, as were intron losses in mosquito genes.

Nevertheless, when the team focused on mosquito chemosensory genes, it saw a relatively stable set of coding sequences overall, with some gene losses or gains affecting specific branches of the system such as genes coding for smell and taste receptors.

Based on these and other findings, the study's authors proposed that the variable ability of Anopheles species to serve as a vector for Plasmodium parasites may largely stem from slight genetic shifts that alter the sequence, function, and expression of chemosensory proteins and mosquito immune system players rather than dramatic gene jettison or acquisition events.

They argued that further exploration of these and other mosquito sequences may help in controlling malaria disease since mosquito vector control has been a key component of successful local malaria control efforts so far.

"[A]n increased understanding of vector biology is crucial for continued progress against malarial disease," the researchers concluded. "These 16 new reference genome assemblies provide a foundation for additional hypothesis generation and testing to further our understanding of the diverse biological traits that determine vectorial capacity."

In an accompanying paper, also published online in Science, members of the same team focused on phylogenetic features in "Afrotropical" mosquito species, including An. gambiae and sister species from the same complex. In addition to unraveling relationships between these Anopheles sister species, the researchers used the phylogenetic tree to track introgression hybridization events between them.

For the most part, this introgression — including sequence swaps that may affect malaria-carrying capabilities — seemed to affect the mosquitoes' autosomal chromosome sequences, they found, while the X chromosomes remained relatively recalcitrant to introgression.

"Our results show that the most efficient [malaria parasite] vectors are not necessarily the most closely-related species, and that traits enhancing vectorial capacity may be gained by gene flow between species," University of Notre Dame biologist Nora Besansky, co-corresponding author on both Science studies, said in a statement.

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