The mosquito Aedes aegypti is the major vector for yellow fever, as well as Dengue fever and chikungunya, making it an important target for disease control. However a detailed physical map of its genome, to aid research efforts into disease prevention and management, is still lacking. Maria Sharakhova from Virginia Tech, USA, and colleagues sought to address this knowledge gap by applying an in situ hybridisation approach to mitotic chromosomes of Ae. aegypti, as published in their recent study in BMC Biology. Sharakova and colleagues went a step further and compared the genomic data they obtained from Ae. aegypti to the genome of the malaria vector Anopheles gambiae, providing further insights into Ae. aegypti evolution. We asked evolutionary biologist Jeffrey Powell from Yale University, USA, what challenges the Ae. aegypti genome presents and why this study marks a significant step forward in our understanding of its genetic composition.
Can you summarise why this study is of particular importance to vector biology research and also more widely to the infectious disease community?
As traditional methods of controlling vectors of human diseases have decreased in their effectiveness (e.g. due to widespread insecticide resistance), alternative methods of control have been desperately sought. Using genetics to control vectors is one of the few viable alternatives. The most effective of what is envisioned is to genetically manipulate populations to be less efficient vectors of pathogens, that is, find genes in the vector that can stop transmission. If such genes could be ‘driven’ into field populations, transmission would be interrupted. If this is ever going to be possible, it is of utmost importance to understand in some detail the genetic make-up of vectors. The study in BMC Biology by Maria Sharakhova and colleagues makes a leap forward in the genetics of one of the most important vectors in the world.
Why is having a physical map of the Aedes aegypti genome, in addition to knowing its genome sequence, so important?
Knowing where genes are on chromosomes allows much better understanding of all kinds of processes. For example, if a gene conferring resistance to transmission of a pathogen is closely linked on a chromosome to a gene conferring insecticide resistance, one could ‘drive’ the resistance gene into a population by applying that insecticide so the pathogen resistant gene would ‘hitch hike’ into the population. On the other hand, if the pathogen resistant gene is closely linked to deleterious genes (e.g. recessive lethal), driving it into population is much more difficult.
To those outside the field it might seem somewhat slow progress to have succeeded in physically mapping only 45 percent of the Aedes aegypti genome several years after it was sequenced. Why is the assembly of this genome such a formidable challenge?
There are two (related) attributes of the Aedes aegypti genome that have been roadblocks to mapping and assembling the genome. First, the majority of the genome is repetitive sequences. Thus, taking stretches of sequences of A, T, C, and G and trying to hook them up into the long linear sequence we know must exist in a chromosome has been almost impossible. To date, the raw sequences have been assembled into a few thousand contigs or supercontigs, about as far as traditional methods of assembling genomes can go. The approach in this paper, to physically assign contigs to linear positions along the chromosome arms is therefore a real breakthrough. This approach, hybridising clones to mitotic chromosomes, is still a problem with the parts of the genome that do not have unique stretches of sequence so that only a single hybridisation occurs. Forty-five percent is a good start and other methods such as traditional mapping by recombination can make good use of this 45 percent of the genome ‘anchor’.
What, in your view, are the most remarkable insights to have emerged from this study?
In addition to the insights into the Aedes aegypti genome, the comparison to the Anopheles gambiae genome is also of interest. These two mosquitoes, vectors of the two most important vector-borne human diseases, have very different genome structures. For example one Mb of the Ae. aegypti genome has about 12 protein-coding genes and 1600 transposable elements (a form of repetitive sequences) while An. gambiae has about 40 protein-coding genes and 200 transposable elements per Mb.
What are the long term implications of these findings?
As noted above, this 45 percent of the genome now securely anchored to the chromosome will greatly aid in attaching the remaining 55 percent by other means such as recombination mapping. This is being done in other labs and we can look forward to a nearly complete assembly in the near future.
Questions from Penelope Austin, Associate Editor for BMC Biology.
More about the researcher(s)
Jeffrey Powell is Professor of ecology and evolutionary biology at the Climate and Energy Institute at Yale University, USA, as well as Adjunct Professor at the School of Forestry and Environmental Studies and the School of Epidemiology and Public Health at Yale University. He received his PhD investigating the population genetics studies of Drosophila at the University of California, Davis, USA, under the supervision of Theodosius Dobzhansky. He then joined Yale University as an Assistant Professor and undertook several sabbaticals during his career at the University of California, USA, University of Rome, Italy, California Institute of Technology, USA, and the University of Cambridge, UK. Powell’s major research interests are in the fields of evolutionary genetics and molecular evolution, largely focusing on Drosophila as a model organism and applying genetic tools to mosquitoes to aid in disease control.