Igor Sharakhov

Education

B.S./M.S. in Biology, Tomsk State University, Tomsk, Russia

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

Postdoc, State University of New York at Buffalo, Buffalo, NY, USA

Postdoc, 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

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 develop new genome assemblies and physical 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). By analyzing mapped genome assemblies of Anopheles gambiae, An. stephensi, An. funestus, An. atroparvus, and An. albimanus, we found that the X chromosome rearrangements occur 3 times faster than autosomal rearrangements pointing to a special role of sex chromosomes in evolution of mosquitoes (Jiang, Peery et al. 2014, Genome Biology; Neafsey, Waterhouse et al. 2015, Science). More recently, we discovered new type of rearrangements in malaria mosquitoes – partial arm translocations in the An. atroparvus and An. albimanus lineages. We also detected nonrandom distribution of large conserved synteny blocks in mosquito genomes suggesting functional or structural constrains to chromosome evolution (Artemov et al. 2017, G3; 2018, BMC Genomics). 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.

Funding: NIH 5R21AI074729, NIH 5R21AI099528, RSF 15-14-20011, NIH 1R21AI135298

Functional effects of chromosome-nuclear envelope interactions

The research goal of this project is to uncover the fundamental mechanisms through which interactions between chromosomes and the periphery of the cell nucleus regulate gene expression. Our experimental analyses of nuclear architecture are complemented and guided by computer simulation in collaboration with Dr. Alexey Onufriev (Department of Computer Science, Virginia Tech). We described a method for modeling the 3D organization of the interphase nucleus, and its application to analysis of chromosome-nuclear envelope attachments of polytene (giant) chromosomes in Drosophila melanogaster salivary glands (Kinney et al. 2014 PLoS One). We used a combined experimental and computational approach to study the effects of chromosome-nuclear envelope attachments on the 3D genome organization of fruit fly salivary gland nuclei. Our modeling demonstrated that nuclear envelope attachments increase the probability of intra-chromosomal contacts and decrease the probability of inter-chromosomal contacts (Kinney et al. 2015 Nucleus). We also used coarse-grained molecular dynamics simulations to study the effects of chromosome-nuclear envelope interactions on the dynamics of regular (non-polytene) interphase chromosomes in the Drosophila nucleus. Our results indicate that chromosome-nuclear envelope attachments may help maintain chromosome territories, while slowing down and limiting chromosome entanglement on timescales comparable to the duration of the interphase (Kinney et al. 2018 Epigenetics Chromatin). This powerful interdisciplinary approach could reveal how the organization and function of the genome in the nuclear space is affected by the chromosome-nuclear envelope attachments and will enable the development of novel approaches to regulate gene expression (Sharakhov et al. 2018 Biochemistry (Mosc)). The research will establish a set of general principles that translate the 'language' of 3D chromosome organization into the 'language' of gene expression, which if of fundamental importance to biology.

Funding: NSF MCB-1715207

Evolutionary relationships 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). 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). Using X chromosome rearrangements in the An. gambiae complex, 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). 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.

Funding: NIH 5R21AI081023, NIH 1R21AI079350

Epigenetic factors in malaria mosquitoes

Active and repressive chromatin marks, small non-coding RNAs, and heterochromatin are now receiving increasing recognition as epigenetic factors that affect gene expression in development and reproduction. To determine the extent of heterochromatin within the An. gambiae genome assembly, we physically mapped genes to the euchromatin-heterochromatin transition zone of polytene chromosomes (George et al. 2010, Insect Molecular Biology). Our study has found that the heterochromatin in An. gambiae accumulates heterochromatin protein 1 (HP1), includes the rDNA locus, and is enriched with essential protein-coding genes important for establishing, maintaining, and modifying chromatin structure (Sharakhova et al. 2010, BMC Genomics). My laboratory team and I have developed a protocol for examining biological effects of an epigenetic drug that reduces repressive chromatin marks (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 may have functions related to An. gambiae reproduction and embryonic development (George, Jensen et al. 2015, Epigenetics Chromatin). 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). Because Y chromosomes can 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. 

Funding: NIH 5R21AI094289

Students

Jiang-tao Liang, jtliang@vt.edu

Duncan Miller, duncanmiller@vt.edu

Varvara Lukyanchikova, lukva@vt.edu

Semen Bondarenko, bondarenko@vt.edu

Kathryn Williamson, kathrw6@vt.edu

The PubMed list:

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

Selected publications (5 years)

Edited book:

Sharakhov, I.V. [ed.] 2015. Protocols for Cytogenetic Mapping of Arthropod Genomes. Boca Raton, FL: CRC Press, Taylor and Francis Group, LLC. 526 Pages. http://www.crcpress.com/product/isbn/9781466598157#.

Reviews:

Sharakhov IV, Bondarenko SM, Artemov GN, Onufriev AV. The Role of Chromosome-Nuclear Envelope Attachments in 3D Genome Organization. Biochemistry (Mosc). 2018 Apr;83(4):350-358.

Sharakhov IV, Artemov GN, Sharakhova MV. Chromosome evolution in malaria mosquitoes inferred from physically mapped genome assemblies. J Bioinform Comput Biol. 2016 Apr;14(2):1630003.

Sharakhov IV, Sharakhova MV. Heterochromatin, histone modifications, and nuclear architecture in disease vectors. Curr Opin Insect Sci. 2015 Aug 1;10:110-117.

Papers in refereed journals:

Artemov GN, Bondarenko SM, Naumenko AN, Stegniy VN, Sharakhova MV, Sharakhov IV. Partial-arm translocations in evolution of malaria mosquitoes revealed by high-coverage physical mapping of the Anopheles atroparvus genome. BMC Genomics. 2018 Apr 23;19(1):278.

Kinney NA, Sharakhov IV, Onufriev AV. Chromosome-nuclear envelope attachments affect interphase chromosome territories and entanglement. Epigenetics Chromatin. 2018 Jan 22;11(1):3.

Anopheles gambiae 1000 Genomes Consortium. Genetic diversity of the African malaria vector Anopheles gambiae. Nature. 2017 Dec 7;552(7683):96-100.

Artemov GN, Peery AN, Jiang X, Tu Z, Stegniy VN, Sharakhova MV, Sharakhov IV.

The Physical Genome Mapping of Anopheles albimanus Corrected Scaffold Misassemblies and Identified Interarm Rearrangements in Genus Anopheles. G3 (Bethesda). 2017 Jan 5;7(1):155-164.

Hall AB, Papathanos PA, Sharma A, Cheng C, Akbari OS, Assour L, Bergman NH, Cagnetti A, Crisanti A, Dottorini T, Fiorentini E, Galizi R, Hnath J, Jiang X, Koren S, Nolan T, Radune D, Sharakhova MV, Steele A, Timoshevskiy VA, Windbichler N, Zhang S, Hahn MW, Phillippy AM, Emrich SJ, Sharakhov IV, Tu ZJ, Besansky NJ. Radical remodeling of the Y chromosome in a recent radiation of malaria mosquitoes. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):E2114-23.

George P, Jensen S, Pogorelcnik R, Lee J, Xing Y, Brasset E, Vaury C, Sharakhov IV.

Increased production of piRNAs from euchromatic clusters and genes in Anopheles gambiae compared with Drosophila melanogaster. Epigenetics Chromatin. 2015 Nov 27;8:50.

Kinney NA, Onufriev AV, Sharakhov IV. Quantified effects of chromosome-nuclear envelope attachments on 3D organization of chromosomes. Nucleus. 2015;6(3):212-24.

Sharma A, Anderson TD, Sharakhov IV. Toxicological assays for testing effects of an epigenetic drug on development, fecundity and survivorship of malaria mosquitoes. J Vis Exp. 2015 Jan 16;(95):52041.

Neafsey DE, Waterhouse RM, Abai MR, Aganezov SS, Alekseyev MA, Allen JE, Amon J, Arcà B, Arensburger P, Artemov G, Assour LA, Basseri H, Berlin A, Birren BW, Blandin SA, Brockman AI, Burkot TR, Burt A, Chan CS, Chauve C, Chiu JC, Christensen M, Costantini C, Davidson VL, Deligianni E, Dottorini T, Dritsou V, Gabriel SB, Guelbeogo WM, Hall AB, Han MV, Hlaing T, Hughes DS, Jenkins AM, Jiang X, Jungreis I, Kakani EG, Kamali M, Kemppainen P, Kennedy RC, Kirmitzoglou IK, Koekemoer LL, Laban N, Langridge N, Lawniczak MK, Lirakis M, Lobo NF, Lowy E, MacCallum RM, Mao C, Maslen G, Mbogo C, McCarthy J, Michel K, Mitchell SN, Moore W, Murphy KA, Naumenko AN, Nolan T, Novoa EM, O'Loughlin S, Oringanje C, Oshaghi MA, Pakpour N, Papathanos PA, Peery AN, Povelones M, Prakash A, Price DP, Rajaraman A, Reimer LJ, Rinker DC, Rokas A, Russell TL, Sagnon N, Sharakhova MV, Shea T, Simão FA, Simard F, Slotman MA, Somboon P, Stegniy V, Struchiner CJ, Thomas GW, Tojo M, Topalis P, Tubio JM, Unger MF, Vontas J, Walton C, Wilding CS, Willis JH, Wu YC, Yan G, Zdobnov EM, Zhou X, Catteruccia F, Christophides GK, Collins FH, Cornman RS, Crisanti A, Donnelly MJ, Emrich SJ, Fontaine MC, Gelbart W, Hahn MW, Hansen IA, Howell PI, Kafatos FC, Kellis M, Lawson D, Louis C, Luckhart S, Muskavitch MA, Ribeiro JM, Riehle MA, Sharakhov IV, Tu Z, Zwiebel LJ, Besansky NJ. Highly evolvable malaria vectors: the genomes of 16 Anopheles mosquitoes. Science. 2015 Jan 2;347(6217):1258522.

Fontaine MC, Pease JB, Steele A, Waterhouse RM, Neafsey DE, Sharakhov IV, Jiang X, Hall AB, Catteruccia F, Kakani E, Mitchell SN, Wu YC, Smith HA, Love RR, Lawniczak MK, Slotman MA, Emrich SJ, Hahn MW, Besansky NJ. Extensive introgression in a malaria vector species complex revealed by phylogenomics. Science. 2015 Jan 2;347(6217):1258524.

Jiang X, Peery A, Hall AB, Sharma A, Chen XG, Waterhouse RM, Komissarov A, Riehle MM, Shouche Y, Sharakhova MV, Lawson D, Pakpour N, Arensburger P, Davidson VL, Eiglmeier K, Emrich S, George P, Kennedy RC, Mane SP, Maslen G, Oringanje C, Qi Y, Settlage R, Tojo M, Tubio JM, Unger MF, Wang B, Vernick KD, Ribeiro JM, James AA, Michel K, Riehle MA, Luckhart S, Sharakhov IV, Tu Z. Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi. Genome Biol. 2014 Sep 23;15(9):459.

Kamali M, Marek PE, Peery A, Antonio-Nkondjio C, Ndo C, Tu Z, Simard F, Sharakhov IV. Multigene phylogenetics reveals temporal diversification of major African malaria vectors. PLoS One. 2014 Apr 4;9(4):e93580.

Kinney NA, Sharakhov IV, Onufriev AV. Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach. PLoS One. 2014 Mar 20;9(3):e91943.

George P, Sharma A, Sharakhov IV. 2D and 3D chromosome painting in malaria mosquitoes. J Vis Exp. 2014 Jan 6;(83):e51173