Maria Sharakhova

Education

• B.S. in Biology, magna cum laude, Tomsk State University, Tomsk, Russia
• Ph.D. in Genetics, Institute of Cytology and Genetics, Novosibirsk, Russia
• Postdoc, University of Notre Dame, Notre Dame, IN, USA
• Postdoc, Virginia Tech, Blacksburg, VA, USA

Professional Membership

• American Society of Tropical Medicine and Hygiene
• American Society of Medical Entomology

Courses Taught

• ENT 5324 Genomics of Disease vectors
• ENT/BIOL 3264 Medical and Veterinary Entomology, Laboratory; guest lectures and laboratory
• ENT 5004 Graduate Student Seminar

Mosquitoes from the family Culicidae are vectors of numerous human diseases such as dengue, Zika, West Nile fevers, malaria, and lymphatic filariasis. Among them, dengue fever and dengue hemorrhagic fever—more severe disease with higher rate mortality, are considered the leading arboviral disease of the 21^st century because of its extraordinarily rapid spread over the globe. The rapid expansion of this disease is a result of the world-wide distribution of its primary vector, Aedes aegypti, which is extremely well-adapted to humans. Zika and dengue fevers threaten half of the world’s human population, including those living in the southern states of the USA. Global climate change raises a concern about emergence of other vector-borne diseases in the USA because of the mosquito range expansion. My laboratory team and I develop modern genomic and cytogenetic tools that enhance the quality of genome assemblies, improve gene annotation, and provide a better framework for comparative and population genomics of mosquitoes. Important epidemiological traits, such as adaptability to diverse climatic conditions, circadian flight activity, time of adult emergence, and egg size are often associated with large structural variations in the mosquito genomes. One of the directions in my research is to identify and characterize such genome rearrangements in mosquitoes. Another direction of my studies focuses on evolution of sex-determining chromosomes in mosquitoes. My research program provides the foundation for the development of novel genome-based approaches for vector control. Below are descriptions of my major research projects.

Projects

1. Sequencing, mapping, and characterization of the culicinae mosquito genomes. The Culicidae family is subdivided into two subfamilies, Anophelinae and Culicinae. My research focuses on sequencing, assembling, and physical mapping of culicinae mosquito genomes. These efforts are complicated because, in contrast to the malaria (Anophelinae) mosquitoes, Culicinae have large genome sizes and poorly developed polytene chromosomes, which are unsuitable for routine genome mapping. Therefore, physical genome mapping for these mosquitoes had been challenging until my discovery of a superior source of mitotic chromosomes – imaginal discs in the larvae of Ae. aegypti (Sharakhova, et al. 2011, PLoS Neglected Tropical Diseases). The initial physical mapping conducted under my supervision assembled 45% of the Ae. aegypti genome onto the mitotic chromosomes (Timoshevskiy et al., 2014, BMC Biology). This study had been a major leap forward in the genetics of one of the most important disease vectors. We determined chromosomal locations of quantitative trait loci (QTL)—genetically mapped regions related to the transmission of diverse pathogens by Ae. aegypti (Timoshevskiy et al., 2013, PLoS Neglected Tropical Diseases). These data are useful for the identification of candidate genes that can be utilized in advanced genome-based vector control strategies. I have been a major contributor to the international consortium on the re-sequencing and re-annotation of the Ae. aegypti genome (the Aedes Genome Working Group). The use of state-of-the-art genomic technologies such as PacBio sequencing, Hi-C scaffolding, optical mapping, and physical mapping have significantly improved the assembly and annotation of the genome and assigned 93.5% of the genome assembly to the chromosomes (Matthews et al., 2018, Nature). I also conduct cytogenetic and genomic studies on other culicine species of medical importance. Among them the most dangerous invasive mosquito species in Europe and North America Ae. albopictus, mosquitoes from the Culex pipiens complex (Naumenko et al., 2015, PLoS ONE; Unger et al., 2015, Parasites and Vectors), and a major vector of the West Nile virus in the USA, Cx. tarsalis. The development of genomic resources and tools is a necessary step for designing and implementing novel genome-based approaches to control mosquitoes that empowers quantitative analyses of variable traits such as vector competence, insecticide resistance, and mosquito behavior.

Funding: R21AI088035 NIH, R21AI0101345 NIH, R21AI099528 NIH, R21AI121853 NIH, R21AI123967 NIH, R21AI135258 NIH, R21AI123967 NIH

2. Chromosomal rearrangements in Aedes mosquitoes. Based on body coloration, two subspecies of Ae. aegypti have been described. The subspecies are remarkably different from each other in their worldwide distribution, association with humans, and ability to transmit pathogens. Our collaborative work demonstrated that Ae. aegypti outside Africa consists of the mixture of two clades that originated in West and East Africa (Moore et al., 2013, PLoS Neglected Tropical Diseases). Ecological, behavioral, and physiological adaptations of mosquitoes related to the pathogen transmission are often associated with structural genome rearrangements, such as inversions. However, chromosomal inversions have never been directly observed in Aedes mosquitoes until our recent study of Ae. aegypti from Senegal (Dickson et al., 2016, PLoS Neglected Tropical Diseases). The recently finished Ae. aegypti reference genome map and additional sequencing on the 10X Genomics platform helped to identify abundant structural rearrangements in the mosquito genome including deletions, insertions, translocations, and inversions (Matthews et al., 2018, Nature). Some of the rearrangements overlap with genomic positions of QTL related to transmission of various pathogens. In my laboratory, we recently employed an innovative Hi-C approach to visualize chromosomal rearrangements in Aedes mosquitoes. The application of Hi-C to studying chromosomal rearrangements in two subspecies of Ae. aegypti in Senegal will determine if inversions can explain the differences in vector competence, geographic distribution, and ecological adaptations of the Ae. aegypti subspecies. The discovery of chromosomal inversions in Ae. aegypti helps us to better understand the underlying genomic determinants of epidemiologically important phenotypic differences and population complexities of aedine mosquitoes.

Funding: R21AI121853 NIH, R21AI123967 NIH

3. Evolution of sex-determining chromosomes in mosquitoes. The genome sequencing of the major vector of arboviruses Ae. aegypti and malaria mosquito Anopheles gambiae revealed striking differences in their genome sizes. The size of the Ae. aegypti genome (1.25 gigabases) is only about one-third of the human genome while five times larger than the An. gambiae genome. Both mosquitoes have three pairs of chromosomes. In An. gambiae, the sex chromosomes, X and Y, are relatively small and easily distinguishable from each other and from the autosomes. In contrast, Ae. aegypti lacks differentiated sex chromosomes, and its sex is determined by a single M-locus on the sex-determining autosome. We characterized the pattern of sex chromosome evolution in mosquitoes using cytogenetic and bioinformatic approaches (Timoshevskiy et al., 2014, BMC Biology). Our work demonstrated that the q arm of the sex-determining chromosome 1 had the lowest gene content and the highest density of repetitive genome elements. These data suggest that the genomic composition of the sex-determining chromosome 1 in Ae. aegypti is influenced by the presence of the male-determination locus and ribosomal genes. Our physical mapping using FISH determined the chromosomal position of the male sex-determining gene Nix and gene myo-sex in Ae. aegypti (Hall et al., 2015, Science; Matthews et al., 2018, Nature). Because only a female mosquito can bite and transmit diseases, the study of the sex-determining chromosomes provides the foundation for novel mosquito control methods that convert female mosquitoes into nonbiting males.

Funding: R01AI123338 NIH

Personnel

Students

• James Michael Hodge, jmhodge@vt.edu
• Chantelle Little, chantellejl@vt.edu  
• Reem Masri, reemm7@vt.edu

Publications

Selected publications (5 years)

* graduate students and postdocs in the Sharakhova lab

The PubMed List

https://www.ncbi.nlm.nih.gov/pubmed/?term=sharakhova

Book chapters:

1.   Sharakhova, M.V., Artemov, G.N., Timoshevskiy, V.A.*, Sharakhov, I.V. 2019. Physical genome mapping using fluorescence in situ hybridization with mosquito chromosomes. In: Insect Genomics. Methods in Molecular Biology. Brown S., Pfrender M. (eds.), vol 1858: pp. 177-194. Humana Press, New York, NY. doi: 10.1007/978-1-4939-8775-7 13.

2.   Sharakhova, M.V., George, P., Timoshevskiy, V. A.*, Sharma, A.*, Peery, A., Sharakhov, I. V. (2015). Mosquitoes (Diptera). In: Protocols for cytogenetic mapping of Arthropod genomes. Igor Sharakhov (ed.), pp. 93-171. CRC Press. Taylor and Francis group. Boca Raton, London, New York.

Reviews:

1.      Sharakhov, I.V., and Sharakhova, M.V. 2015. Heterochromatin, histone modifications, and nuclear architecture in disease vectors. Current Opinion in Insect Science 10:110-117.

2.      Xia, A., Liang, J., Sharakhov, I.V., and Sharakhova, M.V. 2014. Research progress in chromosome maps and physical maps of malaria mosquitoes. Chinese Journal of Vector Biology and Control 25(1):83-86.

Papers in refereed journals:

1.   Matthews, B.J., Dudchenko, O., Kingan, S.B., Koren, S., Antoshechkin, I., Crawford, J.E., Herre, M., Redmond, S.N., Rose, N.H., Weedall, G.D., Wu, Y., Batra, S.S., Brito-Sierra, C.A., Buckingham, S.D., Campbell, C.L., Chan, S., Cox, E., Evans, B.R., Fansiri, T., Filipović, I., Fontaine, A., Gloria-Soria, A., Hall, R., Joardar, V.S., Jones, A.K., Kay, R.G.G., Kodali, V.K., Lee, J., Lycett, G.J., Mitchell, S.N., Muehling, J., Murphy, M.R., Omer, A.D., Partridge, F.A., Peluso, P., Aiden, A.P., Ramasamy, V., Rašić, G., Roy, S., Saavedra-Rodriguez, K., Sharan, S., Sharma, A.*, Smith, M.L., Turner, J., Weakley, A.M., Zhao, Z., Akbari, O.S., Black, W.C. 4th, Cao, H., Darby, A.C., Hill, C.A,. Johnston, J.S., Murphy, T.D., Raikhel, A.S., Sattelle, D.B., Sharakhov, I.V., White, B.J., Zhao, L., Aiden, E.L., Mann, R.S., Lambrechts, L., Powell, J.R., Sharakhova, M.V., Tu Z., Robertson, H.M., McBride, C.S., Hastie, A.R., Korlach, J., Neafsey, D.E., Phillippy, A.M., Vosshall, L.B. 2018. Improved reference genome of Aedes aegypti informs arbovirus vector control. Nature, 563(7732), 501-507. doi:10.1038/s41586-018-0692-z.

      I was responsible for the physical mapping of the Ae. aegypti genome. The chromosomal mapping of the sex determining genes in Ae. aegypti was done under my supervision.

2.   Artemov, G.N., Stegniy, V.N., Sharakhova, M.V., and Sharakhov, I.V. 2018. The development of cytogenetic maps for malaria mosquitoes. Insects, 9(3), pii: E121. doi:10.3390/insects9030121.

3.   Artemov, G.N., Velichevskaya, A.I., Bondarenko, S.M., Karagyan, G.H., Aghayan, S.A., Arakelyan, M.S., Sharakhov, I.V., Sharakhova, M.V. 2018. A standard photomap of the ovarian nurse cell chromosomes for the dominant malaria vector in Europe and Middle East Anopheles sacharovi. Malaria Journal, 17(1):276. doi:10.1186/s12936-018-2428-9.

4.   Artemov, G.N., Bondarenko, S.M., Naumenko, A.N.*, Stegniy, V.N., Sharakhova, M.V., and Sharakhov, I.V. 2018. Partial-arm translocations in evolution of malaria mosquitoes revealed by high-coverage physical mapping of the Anopheles atroparvus genome. BMC Genomics, 19(1):278. doi:10.1186/s12864-018-4663-4.

5.      Artemov, G.N., Gordeev, M.I., Kokhanenko, A.A., Moskaev, A.V., Velichevskaya, A.I., Stegniy, V.N., Sharakhov, I.V., and Sharakhova, M.V. 2018. A standard photomap of ovarian nurse cell chromosomes and inversion polymorphism in Anopheles beklemishevi. Parasites and Vectors, 11(1):211. doi:10.1186/s13071-018-2657-3.

6.      Miller, J.R., Koren, S., Dilley, K.A., Puri, V., Brown, D.M., Harkins, D.M., Thibaud-Nissen, F., Rosen, B., Chen, X.G., Tu, Z., Sharakhov, I.V., Sharakhova, M.V., Sebra, R., Stockwell, T.B., Bergman, N.H., Sutton, G.G., Phillippy, A.M., Piermarini, PM., Shabman, R. S. 2018. Analysis of the Aedes albopictus C6/36 genome provides insight into cell line utility for viral propagation. GIGAScience, 7(3), 1-13. doi:10.1093/gigascience/gix135.

7.      Artemov, G.N., Peery A.N., Jiang, X., Tu, Z., Stegniy, V.N., Sharakhova, M.V., and Sharakhov, I. V. 2017. The physical genome mapping of Anopheles albimanus corrected scaffold misassemblies and identified inter-arm rearrangements in genus Anopheles.” G3 (Bethesda, Md.). 7(1), 155-164. doi:10.1534/g3.116.034959.

8.      Liang, J., Cheng, B., Zhu, G., Wei, Y., Tang, J., Cao, J., Ma, Y., Sharakhova, M.V., Xia, A., and Sharakhov, I.V. 2016. Structural divergence of chromosomes between malaria vectors Anopheles lesteri and Anopheles sinensis. Parasites and Vectors. 9. doi:10.1186/s13071-016-1855-0.

9.      Dickson, L.B., Sharakhova, M.V., Timoshevskiy, V.A.*, Fleming K.L., Caspary A., Sylla M., and Black W.C. 2016. Reproductive incompatibility involving Senegalese Aedes aegypti (L) is associated with chromosome rearrangements. PLoS Neglected Tropical Diseases. 10 (4).  doi: 10.1371/journal. pntd.0004626.

10.  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. Proceedings of the National Academy of Sciences of the USA. 113(15): E2114–E2123. doi: 10.1073/pnas.1525164113.

      Microdissection and FISH of the Y chromosome was conducted under my supervision. 

11.  Hall, A.B., Basu, S., Jiang, X., Qi, Y., Timoshevskiy, V.A.*, Biedler, J.K., Sharakhova, M.V., Elahi, R., Anderson, M.A., Chen, X.G., Sharakhov, I.V., Adelman, Z.N., and Tu, Z. 2015. A male-determining factor in the mosquito Aedes aegypti. Science. 348(6240):1268-70. doi: 10.1126/science.aaa2850. 

Physical mapping of the male sex determining genes was conducted under my supervision.

12.  Artemov, G.N., Sharakhova, M.V., Naumenko, A.N.*, Karagodin, D.A., Baricheva, E.M., Stegniy, V.N., and Sharakhov, I.V. 2015. A standard photomap of ovarian nurse cell chromosomes in the European malaria vector Anopheles atroparvus. Medical and Veterinary Entomology. 29(3):230-7. doi: 10.1111/mve.12113.

13.  Naumenko, A.N.*, Timoshevskiy, V.A.*, Kinney, N.A., Kokhanenko, A.A., deBruyn, B.S., Lovin, D.D., Stegniy, V.N., Severson, D.W., Sharakhov, I.V., Sharakhova, M.V. 2015. Mitotic-chromosome-based physical mapping of the Culex quinquefasciatus genome. PLoS ONE. 10(3): e0115737. doi: 10.1371/journal.pone.0115737.

14.  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. 2; 347(6217):1258522. doi: 10.1126/science.1258522.

      My team and I were involved in the development of genome and chromosome maps for 5 species of mosquitoes. These maps were used to analyze chromosomal evolution in these mosquitoes.

15.  Unger, M.F., Sharakhova, M.V., Harshbarger, A.J., Glass P., and Collins, F.H. 2015. A standard cytogenetic map of Culex quinquefasciatus polytene chromosomes in application for fine-scale physical mapping. Parasites and Vectors. 8:307. doi: 10.1186/s13071-015-0912-4.

16.  Hall, A.B., Timoshevskiy, V.A.*, Sharakhova, M.V., Jiang, X., Basu, S., Anderson, M.A., Hu, W., Sharakhov, I.V., Adelman, Z.N., and Tu, Z. 2014. Insights into the preservation of the homomorphic sex-determining chromosome of Aedes aegypti from the discovery of a male-biased gene tightly linked to the M-locus. Genome, Biology and Evolution. 6(1):179-91. doi: 10.1093/gbe/evu002.

17.  Timoshevskiy, V.A.*, Kinney, N.A., deBruyn, B.S., Mao, C., Tu, Z., Severson DW, Sharakhov, I.V., and Sharakhova, M.V. 2014. Genomic composition and evolution of Aedes aegypti chromosomes revealed by the analysis of physically mapped supercontigs. BMC Biology. 12:27, http://www.biomedcentral.com/1741-7007/12/27.

18.  Liang, J., Sharakhova, M.V., Lan, Q., Zhu, H., Sharakhov, I.V., and Xia A. 2014. A standard cytogenetic map for Anopheles sinensis and chromosome arm homology between the subgenera Anopheles and Cellia. Medical and Veterinary Entomology. 28 Suppl 1:26-32. doi: 10.1111/mve.12048.

19.  Sharakhova, M.V., Antonio-Nkondjio, C., Xia, A., Ndo, C., Awono-Ambene, P., Simard, F., and Sharakhov, I.V. 2014. Polymorphic chromosomal inversions in Anopheles moucheti, a major malaria vector in Central Africa. Medical and Veterinary Entomology. 28(3):337-40. doi: 10.1111/mve. 12037.

20.  Jiang, X., Peery, A., Hall, A., Sharma, A.*, Chen, X.G., Waterhouse, R.M., Komissarov, A., Riehl, 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 Biology. 23; 15(9):459. doi: 10.1186/s13059-014-0459-2.