Researchers in College of Agriculture and Life Sciences at Virginia Tech found unique interactions in the cells of five mosquito species that could be a route to eliminating the ability to transmit malaria and other diseases in the future. The findings were recently published in Nature Communications.
Virginia Tech researchers Igor Sharakhov and Varvara Lukyanchikova were the first to study three-dimensional genome organization in mosquitoes. Illustrated by Max Esterhuizen for Virginia Tech.
People often use insecticides to spray as much as possible to kill mosquitoes. But this control does not distinguish between good and bad insects and also builds resistance between mosquitoes and insects that survive through natural selection and mutation.
After many years of success in controlling mosquito populations in this way, it is currently being reevaluated due to its significantly reduced effectiveness and environmental unfriendliness.
“We have to constantly invent new insecticides,” said Igor Sharakhov, one of the researchers on the project. Fralin Institute of Life Sciences. “With genomic approaches showing more promise, we can engineer a so-called gene drive and create a structure that can suppress a mosquito population or render it incapable of transmitting disease. “
But for practical applications to work, scientists need to understand how the genome – the complete set of genes in a cell – is organized. To get a clear picture of this, Varvara Lukyanchikova, international research leader and a visiting scholar in Department of Entomologyand other members of the project studied five species of mosquitoes with more than 100 million years of evolution between them – about the same as the evolutionary time between mice and humans.
The researchers wanted to examine the genomic organization in malaria mosquitoes with a method that has never been applied to these insects to see if there are any unique traits at the cellular level.
“What we also discovered is that while the mosquito genome is organized similarly to other genomes, it has active and inactive compartments. Now we can see exactly which parts of the genome are working, expressing genes and which are not,” said Lukyanchikova, who also works at the Sharakhov Laboratory and is affiliated with the Institute of Life Sciences. Fralin said. “This could help with the way we use the gene drive system in particular, and is one way we can use the knowledge gained from this study.”
The project was funded for three years by the National Science Foundation.
The team established a technique for mosquito embryos using Hi-C, developed about a decade ago, that studies the three-dimensional architecture of the genome and helps researchers see which regions of the genome genes can be related.
Although the idea is simple, the implementation is a bit more complicated. The researchers took the nuclei and used paraformaldehyde to keep the proteins and DNA interacting in their space while tightly bound. Using a restriction, the researchers cut the DNA and use ligase, an enzyme, to bind the DNA molecules in their nuclear space.
An international team of researchers has established a technique for mosquito embryos using Hi-C, developed about a decade ago, that studies the three-dimensional architecture of the genome and helps researchers see which regions which of the genome can be related to each other. Illustrated by Max Esterhuizen for Virginia Tech.
Using this technique, the researchers extracted nuclei from the cells of five species of mosquitoes, Cellia (An. Coluzzii, An. Merus, An. Stephensi .)), Anopheles (One. atroparvus), and Nyssorhynchus (One. Albimanus). After sequencing the libraries and merging biological clones, the researchers obtained between 60 million and 194 million unique transposable reads for each mosquito species.
Since there are millions of nuclei, it is necessary to generate probabilities. For example, contact A and a contact B. These contacts will not interact in each nucleus. They will only interact in some nuclei. Because of the technique used, estimates can be made of the number of interactions these two touchpoints will have in the cells.
Based on this probability, a heat map can be generated showing how often these two loci are in contact with each other. This is a powerful molecular method for discovering genomic interactions.
The researchers then mapped the heat and compared them between the five mosquito species studied. Some similarities to mammals have been found, but of particular interest are groups of polycombs, long banded rings, two widely spaced regions of the genome, formed by non-polycomb proteins present in other species. In this case, the rings are several megabases apart and remain in strong contact after finding each other in the nucleus.
These loops often have specific cues to block specific interactions, the researchers say, but mosquitoes don’t, suggesting a new way in which the loop works.
Source: VirginiaTech
