Progress 07/01/05 to 06/30/10
Outputs
OUTPUTS: Activities: My primary responsibility is to develop a nationally recognized, extramurally funded research program in genomics and bioinformatics with emphasis on insects of medical importance. I have established a competitive research program at the interface between genomics and organismal biology. My program is supported primarily by NIH grants. I have developed and taught a new graduate course, Genomics of Disease Vectors (ENT 5324), that addresses important questions of adaptation and evolution of arthropod vectors. Events: I presented 12 invited keynote talks and lectures. Services: I have been serving on the University's admission committee for the Interdisciplinary Ph.D. program in GBCB, one of the most prestigious graduate programs at Virginia Tech. I organized and led the effort to include a Bioinformatics Option to the entomology graduate program. Since 2010, I am an editor for the Journal of Insect Science, an international, open access, peer-reviewed journal. Products: I am the author and co-author on 35 peer-reviewed research articles. My work has been published in high-impact scientific journals (PNAS USA, PLoS ONE, Science) and in top-level journals in my field (BMC Genomics, Genetics, Gene, Infection, Genetics and Evolution, Insect Molecular Biology, Journal of Medical Entomology, Malaria Journal, Molecular Genetics and Genomics). Recruiting, advising, and funding graduate and undergraduate students are primary components of my program. One of my Ph.D. students has graduated. Currently, I am advising three Ph.D. students and one M.S. student. Dissemination: 1) In November 2010, the Office of Communications and Marketing of CALS interviewed me in order to promote and publicize my contributions to the college's mission areas. The goal of this activity is to increase awareness of the college's research activities and generate more publicity with our stakeholders outside of Virginia Tech. This is being done through the variety of outlets, including a new blog focused on research in the college. 2) News Releases from Bluefield State College, Bluefield, WV published an article "Nationally recognized entomology researcher presents "Malaria mosquito genomics" research program at BSC" on April 23, 2009. This article is about research that I presented to faculty and students at Bluefield State College. PARTICIPANTS: Collaborators: Jeff Bailey, University of Massachusetts Medical School; Irina Brusentsova, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk; Scotland Leman, Virginia Tech; Zhijian Tu, Virginia Tech; Chris Smith, UCSF; Christophe Antonio-Nkondjio,Cyrille Ndo, Parfait Awono-Ambene, OCEAC, Yaounde, Cameroon; Frederic Simard, Institut de Recherche pour le Developpement (IRD), Montpellier, France. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
A change in knowledge: Mosquitoes of the genus Anopheles are the exclusive vectors of human malaria, which kills about 2 million people each year. Diversification of malaria mosquito lineages is characterized by rapid and repetitive evolution of vectorial capacity. Mosquito speciation and adaptations related to malaria transmission are often associated with chromosomal inversions (genome rearrangements that results from flipping a chromosomal segment by 180 degrees). Identifying the genomic changes associated with the origin and loss of human blood choice, specific ecological and behavioral adaptations, speciation, and ability to support development of a malaria parasite will lead to novel approaches to malaria control. Despite the growing recognition of the importance of chromosomal rearrangements for adaptation and evolution of species, the evolutionary forces responsible for rearrangement origin, maintenance and fixation remain a mystery of evolutionary biology. The highly nonuniform distribution of chromosomal inversions in malaria mosquitoes provides an opportunity to assess the role of genomic landscapes in chromosome-specificity of rearrangement rates. Polymorphic chromosomal inversions predominantly occupy one of five chromosomal arms (2R) in mosquito species and play a fundamental role in adaptation to various environments, thus, facilitating the broad geographic range of these vectors and the malaria they transmit. We performed a comparative genomic study and Bayesian statistical analyses of genomic landscapes of the mosquito chromosomes. Our study provided a clear picture on several important patterns of chromosomal evolution and revealed findings of outstanding interest. First, arm 2R has the highest density of regions involved in segmental duplications that cluster in the breakpoint-rich zone of the arm. Second, despite the paucity of polymorphic inversions on the X chromosome, this chromosome has the fastest rate of inversion fixation and the highest transposable element density. Third, the autosomal arms differ in their tolerance to disruption of syntenic blocks during mosquito evolution. Finally, polymorphic inversions on the 2R arm, the richest gene arm, involved in parallel adaptations in distantly related species, nonrandomly captured similar sets of genes. We concluded that natural selection favors adaptive gene combinations within polymorphic inversions when distant species are exposed to similar environmental pressures. Thus, the genome landscapes and evolutionary histories of rapidly evolving chromosomal arms differ significantly from those of slowly evolving chromosomes. Our study has shown that a unique combination of various types of repeats in each arm, rather than a single type of repetitive element, is responsible for arm-specific rates of rearrangements. Moreover, we have demonstrated that natural selection and drift have different impacts on the sex chromosome and autosome evolution. This paradigm-breaking discoveries call for a reevaluation of the genomic analyses, which must be performed on an arm-by-arm basis using sequences physically mapped to the chromosomes.
Publications
- George, P., M. V. Sharakhova, and I. V. Sharakhov. 2010. High-resolution cytogenetic map for the African malaria vector Anopheles gambiae. Insect Molecular Biology, 19(5): 675-682.
- Xia, A., M. V. Sharakhova, S. C. Leman , Z. Tu, J. A. Bailey, C. D. Smith, and I. V. Sharakhov. 2010. Genome landscape and evolutionary plasticity of chromosomes in malaria mosquitoes. PLoS ONE 5(5): e10592.
- Serazin, A. C., A. N. Dana, M. E. Hillenmeyer, N. F. Lobo, M. B. Coulibaly, M. B. Willard, B. W. Harker, I. V. Sharakhov, F. H. Collins, J. M. Ribeiro, and N. J. Besansky. 2009. Comparative analysis of the global transcriptome of Anopheles funestus from Mali, West Africa. PLoS ONE 19;4(11): e7976.
- Grushko, O. G., M. V. Sharakhova, V. N. Stegnii, and I. V. Sharakhov. 2009. Molecular organization of heterochromatin in malaria mosquitoes of the Anopheles maculipennis subgroup. Gene 448(2): 192-197.
- Xia, A., M. V. Sharakhova, and I. V. Sharakhov. 2008. Reconstructing ancestral autosomal arrangements in the Anopheles gambiae complex. Journal of Computational Biology 15(8):1-16.
- Scali, C., T. Nolan, I. V Sharakhov, M. Sharakhova, A. Crisanti, and F. Catteruccia. 2007. Post-integration behavior of a Minos transposon in the malaria mosquito Anopheles stephensi. Molecular Genetics and Genomics 278: 575-584.
- Riehle, M. M., K. Markianos, L. Lambrechts, A. Xia, I. V. Sharakhov, J. C. Koella, and K. D. Vernick. 2007. A major genetic locus controlling natural Plasmodium falciparum infection is shared by East and West African Anopheles gambiae. Malaria Journal 6: 87.
- White, B. J., F. Santolamazza, L. Kamau, M. Pombi, O. Grushko, K. Mouline, C. Brengues, W. Guelbeogo, M. Coulibaly, J. K. Kayondo, I. V. Sharakhov, F. Simard, V. Petrarca, A. Della Torre, and N. J. Besansky. 2007. Molecular karyotyping of the 2La inversion in Anopheles gambiae. American Journal of Tropical Medicine and Hygiene 76: 334-339.
- Sharakhova, M. V., A. Xia, S. I. McAlister, and I. V. Sharakhov. 2006. A standard cytogenetic photomap for the mosquito Anopheles stephensi (Diptera: Culicidae): application for physical mapping. Journal of Medical Entomology 43: 861-866.
- Sharakhov, I. V., B. J. White, M. V. Sharakhova, J. Kayondo, N. F. Lobo, F. Santolamazza, A. Della Torre, F. Simard, F. H. Collins, and N. J. Besansky. 2006. Breakpoint structure reveals the unique origin of an interspecific chromosomal inversion (2La) in the Anopheles gambiae complex. Proceedings of National Academy of Sciences of the U S A 103: 6258-6262.
- Grushko, O. G., A. M. Rusakova, M. V. Sharakhova, I. V. Sharakhov, and V. N. Stegnii. 2006. Localization of repetitive DNA sequences in the pericentromeric heterochromatin of malarial mosquitoes of the Anopheles maculipennis complex. Tsitologiia 48: 240-245.
- Boikova, T. V., I. V. Sharakhov, S. A. Kopyl, E. Volkova, P. A. Fisher, V. A. Rogachev, T. E. Sebeleva, and S. S. Bogachev. 2005. A combined approach to mapping the proximal border of the right arm of polytene chromosome 2 in Drosophila melanogaster otu 11. Tsitologiia 47: 249-254.
- Sharakhova, M. V., C. Antonio-Nkondjio, A. Xia, C. Ndo, P. Awono-Ambene, F. Simard, and I. V. Sharakhov. 2010. Cytogenetic map for Anopheles nili: application for population genetics and comparative physical mapping. Infection, Genetics and Evolution 10.1016/j.meegid.2010.06.015.
- Sharakhov, I. V., E. M. Baricheva, S. S. Bogachev, P. A. Fisher, E. R. Lapik, V. A. Rogachev, and T. E. Sebeleva. 2005. Specific DNA sequences are associated with nuclear envelopes of pseudonurse cells in Drosophila melanogaster otu 11. Tsitologiia 47: 243-248.
- Sharakhova, M. V., Ai Xia, Z. Tu, Y. S. Shouche, M. F. Unger, and I. V. Sharakhov. 2010. A physical map for an Asian malaria mosquito Anopheles stephensi. American Journal of Tropical Medicine and Hygiene, 83(5):1023-1027.
- Sharakhova, M. V., P. George, I. V. Brusentsova, S. C. Leman, J. A. Bailey, C. D. Smith and I. V. Sharakhov. 2010. Genome mapping and characterization of the Anopheles gambiae heterochromatin. BMC Genomics, 11:459.
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Progress 10/01/08 to 09/30/09
Outputs
OUTPUTS: Anopheles moucheti and An. nili females were collected at several locations in Cameroon. Ovaries were preserved in Carnoy's fixative solution. Chromosomal analysis of 132 half-gravid females of An. nili collected in three locations identified inversion 2Ra. This inversion is rare because it was found only in one individual from Magba, Cameroon. Thus, An. nili populations have a low level of inversion polymorphism, at least in Cameroon. Chromosomal analysis of half-gravid females of An. moucheti collected in Olama and Lepse revealed the presence of polymorphic inversions. At least four different inversions were identified on two chromosomal arms. Of the 12 analyzed An. moucheti mosquitoes, seven carried one or more polymorphic inversions. Four females had both the 2Ra and the 2Rc polymorphic inversions. One female had the 2Rc inversion only, another female had the 2Ra inversion only, and yet another mosquito had four polymorphic inversions on two chromosomal arms. Thus, An. moucheti is a chromosomally polymorphic species and, therefore, inversions can be used for studying population structure in this species. Interestingly, the 2Rc inversion was located near the centromere, which is a rare situation in mosquitoes. The location of at least two rearrangements on the 2R arm is in agreement with the abundance of polymorphic inversions on 2R in An. gambiae and An. funestus. To our knowledge, this is the first description of polymorphic inversions in An. moucheti. We developed a cytogenetic map for An. nili polytene chromosomes. Chromosomal arms were named on the basis of their associations and lengths. The chromosomes were divided into 46 regions in accordance with the An. gambiae and An. funestus maps. This feature will be useful for the mapping of microsatellite markers. To determine chromosome homologies among distant mosquito species, we mapped An. gambiae cDNA probes to An. moucheti and An. nili chromosomes. Probe AG2935 hybridized inside the An. moucheti 2Ra polymorphic inversion and probe AG7039 was located near the pericentric heterochromatin of the 3L chromosome in An. nili. The analysis demonstrated that the An. nili chromosomes have an An. stephensi-like arm association (2+5; 3+4). All An. moucheti chromosomes contact with each other by pericentromeric regions forming a chromocenter. PARTICIPANTS: 1) Igor V. Sharakhov (Principal Investigator) is responsible for the overall design and implementation of the experiments. The PI will be directly responsible for establishing the highpressure chromosome preparation and the primed in situ labelling (PRINS) methods in the laboratory. 2) Maria V. Sharakhova (Research Scientist) is responsible for developing standard high-resolution cytogenetic photomaps for the malaria vectors An. moucheti and An. nili and microsatellite mapping. 3) Antonio Nkondjio (Co-Investigator) is collecting half-gravid females of all members of the An. moucheti and An. nili groups from different ecological environments throughout the distribution area in Cameroon, Burkina Faso, Nigeria, and the Democratic Republic of Congo. TARGET AUDIENCES: 1) Individuals and groups affected by malaria in Africa. 2) Malaria researchers. 3) University students. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Data obtained from various organisms suggest that chromosomal polymorphism is a major mechanism for ecological adaptation. Selection, as it acts on chromosomal inversions, is especially strong and environment-dependent changes in a species' evolutionary dynamics can be seen within a human lifetime. For this reason, identification and characterization of polymorphic inversions in mosquitoes provide valuable tools for studying variations in natural populations. Anopheline mosquitoes are renowned for the presence of polytene chromosomes and chromosomal inversions in various tissues. Therefore, this project takes advantage of the opportunity to develop cytogenetic research tools for taxonomic and population genetics studies of the neglected malaria vectors An. moucheti and An. nili. The development of a cytogenetic map for An. moucheti will allow researchers to perform a characterization of taxonomic status and population structure of An. moucheti and An. nili using fixed and polymorphic chromosomal inversions. Fixed inversion differences among members of each group are the indicators of distinct species and significant differences in frequencies of polymorphic inversions show ecologically distinct populations within An. moucheti s.s. Integrated maps of polytene chromosomes, inversion breakpoints, and microsatellite markers will further stimulate population genetics studies of these neglected malaria vectors.
Publications
- Grushko, O. G., M. V. Sharakhova, V. N. Stegnii, and I. V. Sharakhov. 2009. Molecular organization of heterochromatin in malaria mosquitoes of the Anopheles maculipennis subgroup. Gene 448: 192-7.
- Sharakhova, M. V., C. Antonio-Nkondjio, F. Simard, and I. V. Sharakhov. 2009. Population Cytogenetics of Anopheles moucheti and Anopheles nili. American Journal of Tropical Medicine and Hygiene 80: 966.
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Progress 10/01/07 to 09/30/08
Outputs
OUTPUTS: Chromosomal rearrangements are often associated with differential adaptations of malaria mosquitoes to various environments. Polymorphic inversions tend to cluster in on the 2R arm suggesting existence of hot spots for generating and maintaining rearrangements. Localization of hot and cold spots for rearrangements could be useful for identification of genes involved in ecological adaptations and biologically important gene clusters. The local adaptation model predicts parallelism between the extent of chromosomal polymorphism and evolutionary rates of inversion fixation. Physical maps are useful tools for studying the genome evolution and for relating sequence information to the chromatin structure. We develop a physical genome map of Anopheles stephensi by mapping 206 A. stephensi, A. gambiae, and A. funestus cDNA and BAC clones to 239 chromosome sites. We compared physical maps of A. stephensi, A. funestus, and A. gambiae which belong to the subgenus Cellia. The gene order comparison at the 1.8 Mb resolution has been performed using the Multiple Genome Rearrangements (MRG) and Sorting Permutation by Reversals and block-INterchanGes (SPRING) programs. These results have been reported at the 49th annual Drosophila research conference and at the 56th annual meeting of the American Society of Tropical Medicine and Hygiene (ASTMH). PARTICIPANTS: Collaborators. 1. Craig Coates, Department of Entomology, Texas A&M University, USA. 2. Frederic Simard, the Institut de Recherche en Sciences de la Sante (IRSS), Bobo-Dioulasso, Burkina Faso. 3. Zhijian Tu, Department of Biochemistry, Virginia Tech, USA. 4. Kenneth D. Vernick, Microbiology & Genomics, University of Minnesota, Minneapolis, MN and Institut Pasteur, Paris, France. TARGET AUDIENCES: Researchers and undergraduate and graduate students. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
We have found that inversions fixation rates vary significantly among the chromosomal arms. The small and large blocks of the conserved gene order have been identified among A. stephensi, A. funestus, and A. gambiae. The smallest conserved blocks are found on the 2R and X chromosome. The largest conserved blocks (up to 6 Mb long) have been found on the chromosomal arms 3R and 2L of A. gambiae. Interestingly, these genomic regions are free from polymorphic inversions in the three species. In contrast, X chromosome has the highest rates of inversion fixation but does not have any polymorphic inversions in A. stephensi, A. funestus, or A. gambiae. Thus, we found parallelism between the extent of chromosomal polymorphism and evolutionary rates of inversion fixation for the autosomes but not the sex chromosome. The analysis of the An. gambiae genome identified a significant negative correlation between the number of fixed inversions and the density of Matrix/Scaffold Attachment Regions (M/SARs) suggesting a role of nuclear architecture in determining the chromosome specificity of rearrangement rates. M/SARs can potentially mediate an interaction of specific chromosome sites with a nuclear envelope and affect inter-chromosomal interactions. In addition, we found a positive correlation between the rates of inversion fixations and the simple repeat content on five chromosomal arms. This research program has been designed to impact the field of evolutionary genomics, international collaboration, and student training by raising awareness of the importance of studying genome organization and evolution in vectors of human, animal, and plant diseases. The project transformed our understanding of the mechanisms of chromosome evolution. This research program trained students in insect comparative genomics, molecular cytogenetics, and bioinformatics. The PI mentored graduate and undergraduate students from groups that are underrepresented in biology. An international component to the project included collaboration with research personnel at the Institut de Recherche en Sciences de la Sante, Burkina Faso. The research used an innovative approach to determine mechanisms that facilitates or inhibits genome rearrangements in evolution. The possible association between the nuclear architecture and evolutionary changes in gene order are being tested for the first time.
Publications
- Xia, A., Sharakhova, M.V., and I. V. Sharakhov. 2008. Reconstructing ancestral autosomal arrangements in the Anopheles gambiae Complex. J Comput Biol 15:965-80.
- Sharakhov IV, Sharakhova MV. 2008. Cytogenetic and physical mapping of mosquito genomes. In: Chromosome mapping research developments. Edited by Verrity JF, Abbington LE. New York: Nova Science Publishers, Inc.
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Progress 10/01/06 to 09/30/07
Outputs
OUTPUTS: Activities: Mosquitoes of the genus Anopheles are the exclusive vectors of human malaria, which kills about 2 million people each year. Diversification of malaria mosquito lineages is characterized by rapid and repetitive evolution of vectorial capacity. Mosquito ecological, behavioral, and physiological adaptations related to malaria transmission are often associated with chromosomal inversions (genome rearrangements that result from flipping a chromosomal segment by 180 degrees). It is important to understand how polymorphic inversions regulate the ability of a mosquito to transmit malaria parasites, to adapt to diverse environments, and to aquire incecticide resistance. We have identified the highly rearranged regions that may contain genes important for ecological adaptations and Plasmodium development. We have found contrasting patterns of evolution of a sex cromosome and autosomes. A recent collaborative work with colleagues at the University of Minnesota, Harvard
Medical School, University of California at Davis, and Imperial College London has identified a major malaria-control locus on the 2La chromosome in East African mosquitoes. In order to study the pattern of genome rearrangements we have developed cytogenetic and physical maps for Anopheles stephensi and compared it with the Anopheles gambiae genome. Results were presented at the symposium "Vector-Borne Disease Research: The Road Ahead." Blacksburg, Virginia, October 2006 and RECOMB workshop on comparative genomics, San Diego, CA, September 2007. (2) An interview about malaria and mosquitoes for the news section of the Planet Blacksburg website, 2006. (http://www.planetblacksburg.com/news/conde-091006-malaria.html). 3) Posting non-technical articles on malaria and mosquitoes on the departmental website.
PARTICIPANTS: Individuals: (1) Principal investigator--Igor Sharakhov. (2) Postdoctoral Fellow--Maria Sharakhova. (3) Ph.D. student--Ai Xia. Partner Organizations: 1) National Centre for Cell Science, Pune, India. 2) Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russia. 3) Laboratoire IRD de Recherche sur le Paludisme, OCEAC, Cameroon. 4) Imperial College London, London, UK. 5) University of Minnesota, St. Paul, MN. Collaborators and contacts: Jake Tu, Department of Biochemistry. Donald Mullins, Department of Entomology. Paul Semtner, Department of Entomology. Zach Adelman, Department of Entomology. Jeffrey R Bloomquist, Department of Entomology. Kevin Myles,Department of Entomology. Sally Paulson, Department of Entomology. Training or professional development: I am a Co-Training faculty for NIH/NIGMS R25GM072767 training grant "VT Initiative for Maximizing Student Diversity." 2007-2010. PI: Edward Smith, the Department of Animal and Poultry Sciences,
Virginia Tech. My role is to review applications and advise selected students. So far, I have reviewed two applications. I mentored a VT-PREP student, Phillip George and two undergraduate students.
TARGET AUDIENCES: Target audiences: Researchers and students. Students include international doctoral students, female undergraduate students, and a black female undergraduate student. Efforts: Advising and training of graduate and undergraduate students in genomics and bioinformatics. Formal teaching included BCHM 4052/GBCB 5984 Genomics.
Impacts
Our comparative genomic study provides a new undestanding of evolutionary dynamics of chromosomes. Specifically, the results suggest that autosomal inversions evolve through adaptation while inversions on a sex chromosome play a role in speciation. Detection of a malaria-control locus at the same chromosomal location in both East and West African mosquitoes suggests that the same mechanism of Plasmodium-resistance operates in A. gambiae throughout its entire range. This knowledge can be used for better understanding genome rearrangements and their impact on disease transmission in other mosquitoes. The long-term impact of this research is development of novel strategies for malaria control such as immune regulators or 'smart sprays' that disrupt parasite development in the mosquito.
Publications
- White, B. J., F. Santolamazza, L. Kamau, M. Pombi, O. Grushko, K. Mouline, C. Brengues, W. Guelbeogo, M. Coulibaly, J. K. Kayondo, I. V. Sharakhov, F. Simard, V. Petrarca, A. Della Torre, and N. J. Besansky. 2007. Molecular karyotyping of the 2La inversion in Anopheles gambiae. Am J Trop Med Hyg 76: 334-339.
- Scali, C., T. Nolan, I. V. Sharakhov, M. V. Sharakhova, A. Crisanti, and F. Catteruccia. 2007. Post-integration behavior of a Minos transposon in the malaria mosquito Anopheles stephensi. Mol Genet Genomics 278: 575-584.
- Riehle, M. M., K. Markianos, L. Lambrechts, A. Xia., I. V. Sharakhov, J. C. Koella, and K. D. Vernick. 2007. A major genetic locus controlling natural Plasmodium falciparum infection is shared by East and West African Anopheles gambiae. Malaria J 6(87): 1-7.
- Xia, A., M.V. Sharakhova, I. V. Sharakhov. 2007. Reconstructing an inversion history in the Anopheles gambiae complex. Lecture Notes in Bioinformatics 4751: 136-148.
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Progress 10/01/05 to 09/30/06
Outputs
The chromosomal model of speciation by suppression of recombination suggests that genome rearrangements promote differentiation by acting as a genetic filter between populations. Genomic regions of low recombination, such as the areas around inversion breakpoints and pericentric heterochromatin, may contain genes important for adaptations, speciation, and evolution of vectorial capacity. The availability of polytene chromosomes in malaria mosquitoes provides the opportunity to identify the evolutionary changes in the genome structure. The correspondence of chromosomal elements has been studied between three malaria vectors, Anopheles gambiae, An. funestus, and An. stephensi, the members of different series of the subgenus Cellia. We have developed a low resolution physical map for An. stephensi and compared it with the existing genome maps of An. funestus and An. gambiae. We have found preservation of synteny but substantial shuffling of gene order along corresponding
chromosome arms due to paracentric inversions. Three-way analysis has allowed us to assign the rearrangement events to one of the three lineages. Using a computer algorithm we have calculated the number of rearrangements fixed between the species and identified genomic segments affected the most by inversion fixation. The analysis of the polytene chromosomes has revealed extensive variations in morphology of heterochromatin among An. stephensi, An. funestus, and An. gambiae. An. funestus has only compact heterochromatin in the proximal centromeric region of autosomes, while the An. gambiae centromeric regions consist of mostly diffuse heterochromatin. The types of centric heterochromatin vary among chromosomal arms in An. stephensi. We have used an antibody against the Drosophila Heterochromatin Protein 1 (HP1) to localize the regions of intercalary and pericentric heterochromatin on the mosquito chromosomes. As a result, genomic segments that have undergone transition from
euchromatin to heterochromatin have been identified. Thus, comparison of chromosome structure between distant mosquito species is useful for identifying hot spots or islands of genome evolution.
Impacts
Mosquito ecological, behavioral, and physiological adaptations related to malaria transmission are often associated with chromosomal inversions (genome rearrangements that results from flipping a chromosomal segment by 180 degrees). It is important to understand how polymorphic inversions regulate the ability of a mosquito to transmit malaria parasites and to adapt to diverse environments. This line of research will ultimately lead to the development of novel strategies for malaria control such as immune regulators or 'smart sprays' that disrupt parasite development in the mosquito. Knowledge obtained in this research can be used for better understanding of genome rearrangements and their impact on disease transmission in other mosquitoes. For example, Anopheles quadrimaculatus is a malaria vector in the USA. It is able to transmit the West Nile virus as well. Additional genomic information will help to enhance control of this vector of infectious diseases. Culicine
mosquitoes do not have polytene chromosome and therefore are not suitable for such study. Medically important Culicine mosquitoes in Virginia are Aedes triseriatus (the primary vector of La Crosse virus) and Culex pipiens (the major vector of the West Nile virus).
Publications
- Sharakhova MV, Xia A, McAlister SI, and Sharakhov IV. (2006) A Standard Cytogenetic Photomap for the Mosquito Anopheles stephensi (Diptera: Culicidae) - Application for Physical Mapping. Journal of Medical Entomology 43(5) 861-866.
- Sharakhov IV, White BJ, Sharakhova MV, Kayondo J, Lobo N, Santolamazza F, della Torre A, Simard F, Collins FH, Besansky NJ. (2006) Breakpoint structure reveals the unique origin of an interspecific chromosomal inversion (2La) in the Anopheles gambiae complex. Proc. Natl. Acad. Sci. USA, 103(16): 6258-6262.
- Bojkova TV, Sharakhov IV, Kopyl SA, Volkova E, Fisher PA, Rogachev VA, Sebeleva TE, Bogachev SS (2005) A combined approach to mapping the proximal border of the right arm of polytene chromosome 2 in Drosophila melanogaster otu 11. Tsitologiya (Cytology). 47(3):249-254.
- Sharakhov IV, Baricheva EM, Bogachev SS, Fisher PA, Lapik ER, Rogachev VA, Sebeleva TE, (2005) Specific DNA sequences are associated with nuclear envelopes of pseudonurse cells in Drosophila melanogaster otu 11. Tsitologiya (Cytology). 47(3): 243-248.
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Progress 10/01/04 to 09/30/05
Outputs
We have developed an integrated physical and polytene chromosome map for Anopheles stephensi that includes the breakpoints of all known polymorphic inversions. Cytogenetic maps available for A. stephensi are either drawn or without numbered divisions. For this reason, we have developed a cytogenetic photomap for A. stephensi. We used numered divisions and lettered subdivisions from the map. This photomap proved to be useful for interpreting in situ hybridization results when we mapped 40 conserved A. funestus cDNAs to A. stephensi polytene chromosomes. Sequences of the cDNAs were mapped in silico to the A. gambiae genome as part of a comparative genomic study of synteny, gene order, and sequence conservation between A. stephensi and A. gambiae. The results have indicated that synteny has been preserved at the whole arm level but not at the whole chromosome level, suggesting that reciprocal whole arm translocations have occurred during the evolution of subgenus Cellia.
Despite nearly perfect preservation of synteny, we found substantial shuffling of gene order along corresponding chromosome arms. Our analysis suggests that, in addition to a whole arm translocation, many paracentric inversions have been fixed between A. gambiae and A. stephensi. Our comparative mapping data with A. stephensi and A.gambae, although preliminary, suggest a possibility of a more extensive gene order shuffling on 2R chromosomal arm.
Impacts
Mosquito ecological, behavioral, and physiological adaptations related to malaria transmission are often associated with chromosomal inversions (genome rearrangements that results from flipping a chromosomal segment by 180 degrees). It is important to understand how polymorphic inversions regulate the ability of a mosquito to transmit malaria parasites and to adapt to diverse environments. This line of research will ultimately lead to the development of novel strategies for malaria control such as immune regulators or 'smart sprays' that disrupt parasite development in the mosquito. Knowledge obtained in this research can be used for better understanding of genome rearrangements and their impact on disease transmission in other mosquitoes. For example, Anopheles quadrimaculatus is a malaria vector in the USA. It is able to transmit the West Nile virus as well. Additional genomic information will help to enhance control of this vector of infectious diseases. Culicine
mosquitoes do not have polytene chromosome and therefore are not suitable for such study. Medically important Culicine mosquitoes in Virginia are Aedes triseriatus (the primary vector of La Crosse virus) and Culex pipiens (the major vector of the West Nile virus).
Publications
- Grushko OG, Rusakova AY, Sharakhova MV, Sharakhov IV, Stegnii VN. 2005. Localization repeated DNA sequences in pericentrimeric heterochromatin of malarial mosquitoes from Anopheles maculipennis complex. Tsitologiia (Cytology) in press.
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