Igor Sharakhov

Associate Professor

  • Associate Professor
  • Malaria Mosquitoes
  • Evolutionary Genetics
  • Chromosomes

General

As a member of the Vector-Borne Disease Group at Virginia Tech, I am broadly interested in genomics and evolutionary cytogenetics of mosquitoes – vectors of human infectious diseases. My goal is to understand the genetic mechanisms of mosquito evolution, adaptation, and reproduction. This knowledge can facilitate the development of innovative genome-based approaches for mosquito vector control.

 

Education

B.S. in Biology, magna cum laude, 1989, Tomsk State University, Tomsk, Russia

Ph.D. in Genetics, 1996, Institute of Cytology and Genetics, Novosibirsk, Russia

Postdoc, 1999-2001, State University of New York at Buffalo, Buffalo, NY, USA

Postdoc, 2001-2004, University of Notre Dame, Notre Dame, IN, USA

 

Professional Membership

American Committee of Medical Entomology

American Society of Tropical Medicine and Hygiene

Entomological Society of America

Courses Taught

ENT 5324 Genomics of Disease Vectors

Every year more than one billion people are infected and a million die from vector-borne disease. My laboratory team and I investigate genetic and epigenetic mechanisms that allow the mosquito to adapt, evolve, and reproduce. We develop and implement cytogenetic and genomic tools to understand these mechanisms and to infer historic relationships among species. This timely research addresses problems imposed by the ongoing rapid spread of infectious diseases and provides the foundation for the development of novel genome-based approaches for vector control.

Projects

Genome rearrangements and evolution of malaria vectors. Variation in the ability of mosquitoes to transmit pathogens (vectorial capacity) is determined by many factors, including their behavior, immunity, and life history. Underlying genomic and chromosomal plasticity may result in variation of key traits determining vectorial capacity. The goal of this research project is to determine the patterns, rates, mechanisms, and biological significance of genome rearrangement in malaria mosquitoes. My laboratory team and I have developed physical genome maps for multiple malaria vectors. These maps serve as important tools for scientists to identify potential targets for mosquito control. Using these genome maps we provided evidence that polymorphic inversions on the 2R arms in distantly related species nonrandomly captured similar sets of genes. This finding implies the role of natural selection that acts on similar genetic content of homologous chromosomal arms and creates parallel adaptations in evolutionary distant species (Sharakhova et al. 2011, BMC Evol Biol). We demonstrated that the density of repetitive (“junk”) DNA is much higher on the X (sex) chromosome than on the autosomes in malaria mosquitoes. These repeats could be an underlying cause of the rapid generation of rearrangements on the X (Jiang, Peery et al. 2014, Genome Biology). Indeed, by analyzing mapped genome assemblies of Anopheles gambiae, An. stephensi, An. funestus, An. atroparvus, and An. albimanus, we found that X rearrangements occur 3 times faster than autosomal rearrangements pointing to a special role of sex chromosomes in evolution of mosquitoes (Neafsey, Waterhouse et al. 2015, Science). Knowledge of the dynamic chromosomal evolutionary profile in Anopheles will guide efforts to engineer and introduce sterile or disease-free mosquitoes for successful control of vector populations.

 

Evolutionary history of malaria mosquitoes. Morphologically indistinguishable members of the African An. gambiae complex have remarkably distinct ecological adaptations, geographical distributions, behavior, and the ability to transmit a malaria parasite. My team and I investigate the evolutionary ancestral and derived genomic features in the An. gambiae complex. The ancestral chromosomes were found in An. gambiae and An. merus that are vectors of human malaria, while the derived chromosomes were found in both nonvectors (An. quadriannulatus) and vectors (An. arabiensis). We concluded that the ability to effectively transmit human malaria might have originated repeatedly in the complex (Kamali et al. 2012, PLoS Pathogens). Using X chromosome rearrangements, we have identified the correct species branching order and have shown that lineages leading to the principal vectors of human malaria were among the first to split (Fontaine, Pease et al. 2015, Science). The analysis of historic relationships and temporal diversification among distant African mosquito species placed An. nili at a basal clade that diversified 47.6 million years ago. Other African malaria vectors originated more recently and independently acquired traits related to vectorial capacity (Kamali et al. 2014, PLoS One). This knowledge can be used to identify the evolutionary changes associated with the origin and loss of human blood choice, ecological and behavioral adaptations, and association with human habitats.

 

Epigenetic control of mosquito development and reproduction. The development of novel approaches to control the reproductive output of mosquitoes must include the understanding of how reproduction is regulated. Epigenetic control occurs through modifications that affect chromatin structure but do not change the underlying DNA sequence. Active and repressive chromatin marks, small non-coding RNAs, and repetitive DNA are now receiving increasing recognition as epigenetic factors that affect gene expression in germline development and reproduction. My laboratory team and I have developed a protocol for examining biological effects of an epigenetic drug that reduces repressive chromatin marks. We demonstrated the significant effect of 3-Deazaneplanocin A on suppression of larval development and reduction in number of viable eggs laid by An. gambiae females (Sharma et al. J Vis Exp 2015, 95:52041). We characterized genomic clusters that produce small non-coding Piwi-interacting RNAs (piRNAs) and identified a subset of the piRNA-enriched genes that have functions related to An. gambiae reproduction and embryonic development (George, Jensen et al. 2015, Epigenetics Chromatin). Because Y chromosomes control sex determination and male fertility, we performed chromosome mapping of Y-linked sequences in sibling species of the An. gambiae complex. We demonstrated that these sequences may be variously absent from the Y, not sex biased, or present on the Y without amplification in the complex that radiated only 2 million years ago (Hall, Papathanos, Sharma et al. 2016, PNAS USA). The new information about the heterochromatic Y chromosome will facilitate efforts to reduce female mosquitoes or create sterile males, strategies of interest to research teams across the world. Knowledge about epigenetic factors in vectors of infectious diseases will provide a rich basis for fundamental and applied research aimed at deciphering the mechanisms controlling development and reproduction (Sharakhov, Sharakhova, 2015, Curr Opin Insect Sci).

 

Students

Michael Hodge, jmhodge@vt.edu

Jiang-tao Liang, jtliang@vt.edu

Kerry Maguschak, mkerry14@vt.edu

Lisa Podruchney, lisap95@vt.edu

Selected publications (5 years)

*  graduate students in the Sharakhov lab

1.     Hall, A.B., Papathanos, P., Sharma, A.*, Cheng, C., Akbari, O.S., Assour, L., Bergman, N.H., Cagnetti, A., Crisanti, A., Dottorini, T., Fiorentini, E., Galizi, R., Hnath, H., Jiang, X., Koren, S., Nolan, T., Radune, R., Sharakhova, M.V., Steele, A., Timoshevskiy, V.A., Windbichler, N., Zhang, S.V., Hahn, M.W., Phillippy, A.M., Emrich, S.J., Sharakhov, I.V., Tu, Z., and Besansky, N.J. 2016. Radical remodeling of the Y chromosome in a recent radiation of malaria mosquitoes. Proc Natl Acad Sci USA 113(15):E2114–E2123.

2.     George, P., Jensen. S., Pogorelcnik, R., Lee, J.*, Xing, Y.*, Brasset, E., Vaury, C., and Sharakhov, I.V. 2015. Increased production of piRNAs from euchromatic clusters and genes in Anopheles gambiae compared with Drosophila melanogaster. Epigenetics Chromatin 8:50.

3.     Sharakhov, I.V., and Sharakhova, M.V. 2015. Heterochromatin, histone modifications, and nuclear architecture in disease vectors. Curr Opin Insect Sci 10:110-117.

4.     Sharakhov, I.V. [ed.] 2015. Protocols for Cytogenetic Mapping of Arthropod Genomes. Boca Raton, FL: Taylor  and  Francis Group, LLC. 526 Pages.

5.     Sharma, A.*, Anderson, T.D., and Sharakhov, I.V. 2015. Toxicological assays for testing effects of an epigenetic drug on development, fecundity and survivorship of malaria mosquitoes. J Vis Exp 95:52041

6.     Neafsey, D.E., Waterhouse, R.M., Abai, M.R., Aganezov, S.S., Alekseyev, M.A., Allen, J.E., Amon, J., Arcà, B., Arensburger, P., Artemov, G., Assour, L.A., Basseri. H., Berlin, A., Birren, B.W., Blandin, S.A., Brockman, A.I., Burkot, T.R., Burt, A., Chan, C.S., Chauve, C., Chiu, J.C., Christensen, M., Costantini, C., Davidson, V.L., Deligianni, E., Dottorini, T., Dritsou, V., Gabriel, S.B., Guelbeogo, W.M., Hall, A.B., Han, M.V., Hlaing. T., Hughes, D.S., Jenkins, A.M., Jiang, X., Jungreis, I., Kakani, E.G., Kamali, M., Kemppainen, P., Kennedy, R.C., Kirmitzoglou, I.K., Koekemoer, L.L., Laban, N., Langridge, N., Lawniczak, M.K., Lirakis, M., Lobo, N.F., Lowy, E., MacCallum, R.M., Mao, C., Maslen, G., Mbogo, C., McCarthy, J., Michel, K., Mitchell, S.N., Moore, W., Murphy, K.A., Naumenko, A.N.*, Nolan, T., Novoa, E.M., O'Loughlin, S., Oringanje, C., Oshaghi, M.A., Pakpour, N., Papathanos, P.A., Peery, A.N.*, Povelones, M., Prakash, A., Price, D.P., Rajaraman, A., Reimer, L.J., Rinker, D.C., Rokas, A., Russell, T.L., Sagnon, N., Sharakhova, M.V., Shea, T., Simão, F.A., Simard, F., Slotman, M.A., Somboon, P., Stegniy, V., Struchiner, C.J., Thomas, G.W., Tojo, M., Topalis, P., Tubio, J.M., Unger, M.F., Vontas, J., Walton, C., Wilding, C.S., Willis, J.H., Wu, Y.C., Yan, G., Zdobnov, E.M., Zhou, X., Catteruccia, F., Christophides, G.K., Collins, F.H., Cornman, R.S., Crisanti, A., Donnelly, M.J., Emrich, S.J., Fontaine, M.C., Gelbart, W., Hahn, M.W., Hansen, I.A., Howell, P.I., Kafatos, F.C., Kellis, M., Lawson, D., Louis, C., Luckhart, S., Muskavitch, M.A., Ribeiro, J.M., Riehle, M.A., Sharakhov, I.V., Tu, Z., Zwiebel, L.J., and Besansky, N.J. 2015. Highly evolvable malaria vectors: the genomes of 16 Anopheles mosquitoes. Science 347(6217):1258522.

7.     Fontaine, M.C., Pease, J.B., Steele, A., Waterhouse, R.M., Neafsey, D.E., Sharakhov, I.V., Jiang, X., Hall, A.B., Catteruccia, F., Kakani, E., Mitchell, S.N., Wu, Y.C., Smith, H.A., Love, R.R., Lawniczak, M.K., Slotman, M.A., Emrich, S.J., Hahn, M.W., and Besansky, N.J. 2015. Extensive introgression in a malaria vector species complex revealed by phylogenomics. Science 347 (6217):1258524.

8.     Jiang, X., Peery, A.*, Hall, A.B., Sharma, A.*, Chen, X.G., Waterhouse, R.M., Komissarov, A., Riehle, M.M., Shouche, Y., Sharakhova, M.V., Lawson, D., Pakpour, N., Arensburger. P., Davidson, V.L., Eiglmeier, K., Emrich, S., George, P.*, Kennedy, R.C., Mane, S.P., Maslen, G., Oringanje, C., Qi, Y., Settlage, R., Tojo, M., Tubio, J.M., Unger, M.F., Wang, B., Vernick, K.D., Ribeiro, J.M., James, A.A., Michel, K., Riehle, M.A., Luckhart, S., Sharakhov, I.V., and Tu, Z. 2014. Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi. Genome Biol 15(9):459.

9.     Sharakhova, M.V., Peery, A.*, Antonio-Nkondjio, C., Xia, A.*, Ndo, C., Awono-Ambene, P., Simard, F., and Sharakhov, I.V. 2013. Cytogenetic analysis of Anopheles ovengensis revealed high structural divergence of chromosomes in the Anopheles nili group. Infect Genet Evol 16:341-8.

10.  Kamali, M.*, Xia, A.*, Tu, Z., Sharakhov, I.V. 2012. A new chromosomal phylogeny supports the repeated origin of vectorial capacity in malaria mosquitoes of the Anopheles gambiae complex. PLoS Pathog 8(10):e1002960.

Igor Sharakhov