Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent

eLife

Volumn 5, Issue MARCH2016, 2016, Pages

  Imamura, Hideo ^a   Downing, Tim ^b,c,m   van den Broeck, Frederik ^a   Sanders, Mandy J ^b   Rijal, Suman ^d   Sundar, Shyam ^e   Mannaert, An ^a   Vanaerschot, Manu ^a,n   Berg, Maya ^a   de Muylder, Géraldine ^a   Dumetz, Franck ^a   Cuypers, Bart ^a   Maes, Ilse ^a   Domagalska, Malgorzata ^a   Decuypere, Saskia ^a,f   Rai, Keshav ^d,o   Uranw, Surendra ^d   Bhattarai, Narayan Raj ^d   Khanal, Basudha ^d   Prajapati, Vijay Kumar ^e,p   Sharma, Smriti ^e   Stark, Olivia ^g   Schönian, Gabriele ^g   de Koning, Harry P ^h   Settimo, Luca ^h,i   Vanhollebeke, Benoit ^j   Roy, Syamal ^k   Ostyn, Bart ^a   Boelaert, Marleen ^a   Maes, Louis ^l   Berriman, Matthew ^b   Dujardin, Jean Claude ^a,l   Cotton, James A ^b   more..

^a INSTITUTE OF TROPICAL MEDICINE   (Belgium)

^b WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^c NATIONAL UNIVERSITY OF IRELAND   (Ireland)

^d B P KOIRALA INSTITUTE OF HEALTH SCIENCES   (Nepal)

^e BANARAS HINDU UNIVERSITY   (India)

^f UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^g CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^h UNIVERSITY OF GLASGOW   (United Kingdom)

ⁱ NORTHEASTERN UNIVERSITY   (United States)

^j UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

^k INDIAN INSTITUTE OF CHEMICAL BIOLOGY   (India)

^l UNIVERSITY OF ANTWERP   (Belgium)

^m DUBLIN CITY UNIVERSITY   (Ireland)

ⁿ New York Presbyterian Columbia University Medical Center   (United States)

^o WEST BENGAL STATE UNIVERSITY   (India)

^p CENTRAL UNIVERSITY OF RAJASTHAN   (India)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMONY DERIVATIVE; AQUAGLYCEROPORIN; MILTEFOSINE; PENTAVALENT ANTIMONY; UNCLASSIFIED DRUG; ANTIMONY; ANTIPROTOZOAL AGENT; AQUAPORIN 1;

ANEUPLOIDY; ARTICLE; COPY NUMBER VARIATION; EPIDEMIC; GENE EXPRESSION; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE MUTATION; GENE SEQUENCE; GENETIC IDENTIFICATION; GENOMICS; HAPLOTYPE; HUMAN; INDIA; LEISHMANIA DONOVANI; MAJOR CLINICAL STUDY; MOLECULAR CLOCK; MOLECULAR CLONING; NONHUMAN; PHENOTYPE; PHYLOGENY; POLYMERASE CHAIN REACTION; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; SINGLE NUCLEOTIDE POLYMORPHISM; VISCERAL LEISHMANIASIS; CLASSIFICATION; DNA SEQUENCE; DRUG EFFECTS; DRUG RESISTANCE; GENETIC RECOMBINATION; GENETIC VARIATION; GENETICS; GENOME; ISOLATION AND PURIFICATION; LEISHMANIASIS, VISCERAL; MOLECULAR EPIDEMIOLOGY; MOLECULAR EVOLUTION; NEPAL; PARASITOLOGY;

ANTIMONY; ANTIPROTOZOAL AGENTS; AQUAPORIN 1; DRUG RESISTANCE; EPIDEMICS; EVOLUTION, MOLECULAR; GENETIC VARIATION; GENOME, PROTOZOAN; HUMANS; INDIA; LEISHMANIA DONOVANI; LEISHMANIASIS, VISCERAL; MOLECULAR EPIDEMIOLOGY; NEPAL; RECOMBINATION, GENETIC; SEQUENCE ANALYSIS, DNA;

EID: 84962249121     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.12613     Document Type: Article

References (81)

1. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA. 2012. An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65. doi:10.1038/nature11632
2. Alam MZ, Kuhls K, Schweynoch C, Sundar S, Rijal S, Shamsuzzaman AK, Raju BV, Raju BV, Salotra P, Dujardin JC, Schönian G. 2009. Multilocus microsatellite typing (mLMT) reveals genetic homogeneity of leishmania donovani strains in the indian subcontinent. Infection, Genetics and Evolution 9:24–31. doi:10.1016/j.meegid.2008.09.005
3. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search tool. Journal of Molecular Biology 215:403–410. doi:10.1016/S0022-2836(05)80360-2
4. Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J, Jannin J, den Boer M, WHO Leishmaniasis Control Team. 2012. Leishmaniasis worldwide and global estimates of its incidence. PloS One 7:e35671. doi:10.1371/journal.pone.0035671
5. Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, Menard D. 2014. A molecular marker of artemisinin-resistant plasmodium falciparum malaria. Nature 505:50–55. doi:10.1038/nature12876
6. Baker N, Glover L, Munday JC, Aguinaga Andres D, Barrett MP, de Koning HP, Horn D. 2012. Aquaglyceroporin 2 controls susceptibility to melarsoprol and pentamidine in african trypanosomes. Proceedings of the National Academy of Sciences of the United States of America 109:10996–11001. doi:10.1073/pnas.1202885109
7. Boelaert M, Meheus F, Sanchez A, Singh SP, Vanlerberghe V, Picado A, Meessen B, Sundar S. 2009. The poorest of the poor: a poverty appraisal of households affected by visceral leishmaniasis in Bihar, India. Tropical Medicine &International Health 14:639–644. doi:10.1111/j.1365-3156.2009.02279.x
8. Brotherton MC, Bourassa S, Leprohon P, Légaré D, Poirier GG, Droit A, Ouellette M. 2013. Proteomic and genomic analyses of antimony resistant Leishmania infantum mutant. PLoS One 8:e81899. doi:10.1371/journal.pone.0081899
9. Busing FMTA, Meijer E, Van Der Leiden R. 1999. Delete-M Jackknife for Unequal M. Statistics and Computing 9: 3–8.
10. Carver T, Berriman M, Tivey A, Patel C, Böhme U, Barrell BG, Parkhill J, Rajandream MA. 2008. Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database. Bioinformatics 24:2672–2676. doi:10.1093/bioinformatics/btn529
11. Cheeseman IH, Miller BA, Nair S, Nkhoma S, Tan A, Tan JC, Al Saai S, Phyo AP, Moo CL, Lwin KM, McGready R, Ashley E, Imwong M, Stepniewska K, Yi P, Dondorp AM, Mayxay M, Newton PN, White NJ, Nosten F, Ferdig MT, Anderson TJ. 2012. A major genome region underlying artemisinin resistance in malaria. Science 336:79–82. doi:10.1126/science.1215966
12. Chowdhury R, Mondal D, Chowdhury V, Faria S, Alvar J, Nabi SG, Boelaert M, Dash AP. 2014. How far are we from visceral leishmaniasis elimination in Bangladesh? an assessment of epidemiological surveillance data. PLoS Neglected Tropical Diseases 8:e3020. doi:10.1371/journal.pntd.0003020
13. Decuypere S, Rijal S, Yardley V, De Doncker S, Laurent T, Khanal B, Chappuis F, Dujardin JC. 2005. Gene expression analysis of the mechanism of natural Sb(V) resistance in Leishmania donovani isolates from Nepal. Antimicrobial Agents and Chemotherapy 49:4616–4621. doi:10.1128/AAC.49.11.4616-4621.2005
14. Decuypere S, Vanaerschot M, Brunker K, Imamura H, Müller S, Khanal B, Rijal S, Dujardin JC, Coombs GH. 2012. Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background. PLoS Neglected Tropical Diseases 6:e1514. doi:10.1371/journal.pntd.0001514
15. den Boer M, Argaw D, Jannin J, Alvar J. 2011. Leishmaniasis impact and treatment access. Clinical Microbiology and Infection 17:1471–1477. doi:10.1111/j.1469-0691.2011.03635.x
16. Denton H, McGregor JC, Coombs GH. 2004. Reduction of anti-leishmanial pentavalent antimonial drugs by a parasite-specific thiol-dependent reductase, TDR1. The Biochemical Journal 381:405–412. doi:10.1042/BJ20040283
17. DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, del Angel G, Rivas MA, McKennaHanna AM, McKennaRivas AMA, Fennell TJ, Kernytsky AM, Sivachenko AY, Cibulskis K, Gabriel SB, Altshuler D, Daly MJ. 2011. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nature Genetics 43:491–498. doi:10.1038/ng.806
18. Do R, Balick D, Li H, Adzhubei I, Sunyaev S, Reich D. 2015. No evidence that selection has been less effective at removing deleterious mutations in Europeans than in Africans. Nature Genetics 47:126–131. doi:10.1038/ng.3186
19. Downing T, Imamura H, Decuypere S, Clark TG, Coombs GH, Cotton JA, Hilley JD, de Doncker S, Maes I, Mottram JC, Quail MA, Rijal S, Sanders M, Schönian G, Stark O, Sundar S, Vanaerschot M, Hertz-Fowler C, Dujardin JC, Berriman M. 2011. Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. Genome Research 21:2143–2156. doi:10.1101/gr.123430.111
20. Downing T, Stark O, Vanaerschot M, Imamura H, Sanders M, Decuypere S, de Doncker S, Maes I, Rijal S, Sundar S, Dujardin J-C, Berriman M, Schönian G. 2012. Genome-wide SNP and microsatellite variation illuminate population-level epidemiology in the Leishmania donovani species complex. Infection, Genetics and Evolution 12:149–159. doi:10.1016/j.meegid.2011.11.005
21. Drummond AJ, Suchard MA, Xie D, Rambaut A. 2012. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Molecular Biology and Evolution 29:1969–1973. doi:10.1093/molbev/mss075
22. Dye C, Wolpert DM. 1988. Earthquakes, influenza and cycles of Indian kala-azar. Transactions of the Royal Society of Tropical Medicine and Hygiene 82:843–850.
23. Ebersberger I, Metzler D, Schwarz C, Pääbo S. 2002. Genomewide comparison of DNA sequences between humans and chimpanzees. American Journal of Human Genetics 70:1490–1497. doi:10.1086/340787
24. Evanno G, Regnaut S, Goudet J. 2005. Detecting the number of clusters of individuals using the software structure: a simulation study. Molecular Ecology 14:2611–2620. doi:10.1111/j.1365-294X.2005.02553.x
25. Fernandes AC, Soares DC, Saraiva EM, Meyer-Fernandes JR, Souto-Padrón T. 2013. Different secreted phosphatase activities in Leishmania amazonensis. FEMS Microbiology Letters 340:117–128. doi:10.1111/1574-6968.12080
26. Freudenberg-Hua Y, Freudenberg J, Kluck N, Cichon S, Propping P, Nöthen MM. 2003. Single nucleotide variation analysis in 65 candidate genes for CNS disorders in a representative sample of the European population. Genome Research 13:2271–2276. doi:10.1101/gr.1299703
27. Frézard F, Demicheli C, Ferreira CS, Costa MA. 2001. Glutathione-induced conversion of pentavalent antimony to trivalent antimony in meglumine antimoniate. Antimicrobial Agents and Chemotherapy 45:913–916. doi:10.1128/AAC.45.3.913-916.2001
28. Garrison E, Marth G. 2012. Haplotype-based variant detection from short-read sequencing. ar14:1207.3907.
29. Gibson ME. 1983. The identification of kala-azar and the discovery of Leishmania donovani. Medical History 27: 203–213.
30. Gourbal B, Sonuc N, Bhattacharjee H, Legare D, Sundar S, Ouellette M, Rosen BP, Mukhopadhyay R. 2004. Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. The Journal of Biological Chemistry 279:31010–31017. doi:10.1074/jbc.M403959200
31. Gutenkunst RN, Hernandez RD, Williamson SH, Bustamante CD. 2009. Inferring the joint demographic history of multiple populations from multidimensional SNP frequency data. PLoS Genetics 5:e1000695. doi:10.1371/journal.pgen.1000695
32. Han E, Sinsheimer JS, Novembre J. 2014. Characterizing bias in population genetic inferences from low-coverage sequencing data. Molecular Biology and Evolution 31:723–735. doi:10.1093/molbev/mst229
33. Hudson RR, Kaplan NL. 1985. Statistical properties of the number of recombination events in the history of a sample of DNA sequences. Genetics 111:147–164.
34. Huson DH, Bryant D. 2006. Application of phylogenetic networks in evolutionary studies. Molecular Biology and Evolution 23:254–267. doi:10.1093/molbev/msj030
35. Iqbal Z, Caccamo M, Turner I, Flicek P, McVean G. 2012. De novo assembly and genotyping of variants using colored de Bruijn graphs. Nature Genetics 44:226–232. doi:10.1038/ng.1028
36. Kunsch HR. 1989. The Jackknife and the Bootstrap for General Stationary Observations. The Annals of Statistics 17:1217–1241. doi:10.1214/aos/1176347265
37. Lakhal-Naouar I, Jardim A, Strasser R, Luo S, Kozakai Y, Nakhasi HL, Duncan RC. 2012. Leishmania donovani argininosuccinate synthase is an active enzyme associated with parasite pathogenesis. PLoS Neglected Tropical Diseases 6:e1849. doi:10.1371/journal.pntd.0001849
38. Lawson DJ, Hellenthal G, Myers S, Falush D. 2012. Inference of population structure using dense haplotype data. PLoS Genetics 8:e1002453. doi:10.1371/journal.pgen.1002453
39. Leprohon P, Légaré D, Raymond F, Madore E, Hardiman G, Corbeil J, Ouellette M. 2009. Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum. Nucleic Acids Research 37:1387–1399. doi:10.1093/nar/gkn1069
40. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R.1000 Genome Project Data Processing Subgroup. 2009. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078–2079. doi:10.1093/bioinformatics/btp352
41. Li N, Stephens M. 2003. Modeling linkage disequilibrium and identifying recombination hotspots using single- nucleotide polymorphism data. Genetics 165:2213–2233.
42. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Lim S, AlMazroa MA, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Abdulhak AB, Birbeck G, Blyth F, Bolliger I, Lim S, Bucello C, Lim S, Burney P, Carapetis J, Chen H, Chou D, Lim S, Coffeng LE, Lim S, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Lim S, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Foreman K, Forouzanfar MH, Fowkes FGR, Franklin R, Fransen M, Foreman K, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Foreman K, Khoo J-P, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Memish ZA, Memish ZA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Foreman K, Mulholland K, Nair MN, Naldi L, Narayan KMV, Foreman K, Foreman K, O’Donnell M, Omer SB, Foreman K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA, Porrini E, Pourmalek F, Raju M, Ranganathan D, Lim S, Rein DB, Remuzzi G, Rivara FP, Roberts T, De León FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Foreman K, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Lim S, Wagner GR, Naghavi M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh P-H, Yip P, Zabetian A, Zheng Z-J, Lopez AD, Murray CJL, Shibuya K, Aboyans V, Memish ZA. 2012. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. The Lancet 380: 2095–2128. doi:10.1016/S0140-6736(12)61728-0
43. Lukes J, Mauricio IL, Schönian G, Dujardin JC, Soteriadou K, Dedet JP, Kuhls K, Tintaya KW, Jirku° M, Chocholova´ E, Haralambous C, Pratlong F, Oborník M, Horák A, Ayala FJ, Miles MA. 2007. Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomy. Proceedings of the National Academy of Sciences of the United States of America 104:9375–9380. doi:10.1073/pnas.0703678104
44. Lynch M. 2008. Estimation of nucleotide diversity, disequilibrium coefficients, and mutation rates from high- coverage genome-sequencing projects. Molecular Biology and Evolution 25:2409–2419. doi:10.1093/molbev/msn185
45. Mauricio IL, Yeo M, Baghaei M, Doto D, Pratlong F, Zemanova E, Dedet JP, Lukes J, Miles MA. 2006. Towards multilocus sequence typing of the Leishmania donovani complex: resolving genotypes and haplotypes for five polymorphic metabolic enzymes (ASAT, GPI, NH1, NH2, PGD). International Journal for Parasitology 36:757– 769. doi:10.1016/j.ijpara.2006.03.006
46. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Hanna M, DePristo MA. 2010. The Genome Analysis Toolkit: a MapReduce framework for analyzing next- generation DNA sequencing data. Genome Research 20:1297–1303. doi:10.1101/gr.107524.110
47. Miotto O, Almagro-Garcia J, Manske M, Macinnis B, Campino S, Rockett KA, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Duong S, Nguon C, Chuor CM, Saunders D, ManskeSe MY, Lon C, Fukuda MM, Amenga-Etego L, Hodgson AV, Asoala V, Imwong M, Takala-Harrison S, Nosten F, Su XZ, Ringwald P, Ariey F, Dolecek C, Hien TT, Boni MF, Thai CQ, Amambua-Ngwa A, Conway DJ, Djimdé AA, Doumbo OK, Zongo I, Ouedraogo JB, Alcock D, Drury E, Auburn S, Koch O, Sanders M, Hubbart C, Maslen G, Ruano-Rubio V, Jyothi D, Miles A, O’Brien J, Gamble C, Oyola SO, Rayner JC, Newbold CI, Berriman M, Spencer CC, McVean G, Day NP, White NJ, Bethell D, Dondorp AM, Plowe CV, Fairhurst RM, Kwiatkowski DP. 2013. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nature Genetics 45:648–655. doi:10.1038/ng.2624
48. Miotto O, Amato R, Ashley EA, MacInnis B, Almagro-Garcia J, Amaratunga C, Lim P, Mead D, Oyola SO, Dhorda M, Imwong M, Woodrow C, Manske M, Stalker J, Drury E, Campino S, Amenga-Etego L, Thanh TN, Tran HT, Ringwald P, Bethell D, Nosten F, Amato R, Pukrittayakamee S, Chotivanich K, Chuor CM, Nguon C, Suon S, Sreng S, Newton PN, Mayxay M, Khanthavong M, Hongvanthong B, Htut Y, Han KT, Kyaw MP, Faiz MA, Fanello CI, Onyamboko M, Mokuolu OA, Jacob CG, Takala-Harrison S, Plowe CV, Day NP, Dondorp AM, Spencer CC, McVean G, Fairhurst RM, White NJ, Kwiatkowski DP. 2015. Genetic architecture of artemisinin- resistant Plasmodium falciparum. Nature Genetics 47:226–234. doi:10.1038/ng.3189
49. Monte-Neto R, Laffitte MC, Leprohon P, Reis P, Frézard F, Ouellette M. 2015. Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis. PLoS Neglected Tropical Diseases 9:e0003476. doi:10.1371/journal.pntd.0003476
50. Moorjani P, Patterson N, Hirschhorn JN, Keinan A, Hao L, Atzmon G, Burns E, Ostrer H, Price AL, Reich D. 2011. The history of African gene flow into Southern Europeans, Levantines, and Jews. PLoS Genetics 7:e1001373. doi:10.1371/journal.pgen.1001373
51. Mukherjee A, Boisvert S, Monte-Neto RL, Coelho AC, Raymond F, Mukhopadhyay R, Corbeil J, Ouellette M. 2013. Telomeric gene deletion and intrachromosomal amplification in antimony-resistant Leishmania. Molecular Microbiology 88:189–202. doi:10.1111/mmi.12178
52. Mukhopadhyay R, Mukherjee S, Mukherjee B, Naskar K, Mondal D, Decuypere S, Ostyn B, Prajapati VK, Sundar S, Dujardin JC, Roy S. 2011. Characterisation of antimony-resistant Leishmania donovani isolates: biochemical and biophysical studies and interaction with host cells. International Journal for Parasitology 41:1311–1321. doi:10.1016/j.ijpara.2011.07.013
53. Newby ZE, O’Connell J, Robles-Colmenares Y, Khademi S, Miercke LJ, Stroud RM. 2008. Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparum. Nature Structural &Molecular Biology 15:619–625. doi:10.1038/nsmb.1431
54. Ostyn B, Gidwani K, Khanal B, Picado A, Chappuis F, Singh SP, Khanal B, Sundar S, Boelaert M. 2011. Incidence of symptomatic and asymptomatic Leishmania donovani infections in high-endemic foci in India and Nepal: a prospective study. PLoS Neglected Tropical Diseases 5:e1284. doi:10.1371/journal.pntd.0001284
55. Paradis E, Claude J, Strimmer K. 2004. APE: Analyses of Phylogenetics and Evolution in R language. Bioinformatics 20:289–290.
56. Patterson N, Moorjani P, Luo Y, Mallick S, Rohland N, Zhan Y, Genschoreck T, Webster T, Reich D. 2012. Ancient admixture in human history. Genetics 192:1065–1093. doi:10.1534/genetics.112.145037
57. Pigott DM, Bhatt S, Golding N, Duda KA, Battle KE, Brady OJ, Messina JP, Balard Y, Bastien P, Pratlong F, Brownstein JS, Freifeld CC, Mekaru SR, Gething PW, George DB, Myers MF, Reithinger R, Hay SI. 2014. Global distribution maps of the leishmaniases. eLife 3:e02851. doi:10.7554/eLife.02851
58. Plourde M, Ubeda JM, Mandal G, Monte-Neto RL, Mukhopadhyay R, Ouellette M. 2015. Generation of an aquaglyceroporin AQP1 null mutant in Leishmania major. Molecular and Biochemical Parasitology 201:108–111. doi:10.1016/j.molbiopara.2015.07.003
59. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. 2006. Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics 38:904–909. doi:10.1038/ng1847
60. Pritchard JK, Stephens M, Donnelly P. 2000. Inference of population structure using multilocus genotype data. Genetics 155:945–959.
61. Quispe Tintaya KW, Ying X, Dedet JP, Rijal S, De Bolle X, Dujardin JC. 2004. Antigen genes for molecular epidemiology of leishmaniasis: polymorphism of cysteine proteinase B and surface metalloprotease glycoprotein 63 in the Leishmania donovani complex. The Journal of Infectious Diseases 189:1035–1043. doi:10.1086/382049
62. Reich D, Thangaraj K, Patterson N, Price AL, Singh L. 2009. Reconstructing Indian population history. Nature 461:489–494. doi:10.1038/nature08365
63. Rijal S, Ostyn B, Uranw S, Rai K, Bhattarai NR, Dorlo TP, Beijnen JH, Vanaerschot M, Decuypere S, Dhakal SS, Das ML, RaiKarki KP, Singh R, Boelaert M, Dujardin JC. 2013. Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance. Clinical Infectious Diseases 56:1530–1538. doi:10.1093/cid/cit102
64. Rijal S, Yardley V, Chappuis F, Decuypere S, Khanal B, Singh R, Boelaert M, De Doncker S, Croft S, Dujardin JC. 2007. Antimonial treatment of visceral leishmaniasis: are current in vitro susceptibility assays adequate for prognosis of in vivo therapy outcome? Microbes and Infection 9:529–535. doi:10.1016/j.micinf.2007.01.009
65. Rogers MB, Hilley JD, Dickens NJ, Wilkes J, Bates PA, Depledge DP, Harris D, Her Y, Herzyk P, Imamura H, Otto TD, Sanders M, Seeger K, Dujardin JC, Berriman M, Smith DF, Hertz-Fowler C, Mottram JC. 2011. Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania. Genome Research 21:2129–2142. doi:10.1101/gr.122945.111
66. Roze D, Michod RE. 2010. Deleterious mutations and selection for sex in finite diploid populations. Genetics 184:1095–1112. doi:10.1534/genetics.109.108258
67. Sali A, Blundell TL. 1993. Comparative protein modelling by satisfaction of spatial restraints. Journal of Molecular Biology 234:779–815. doi:10.1006/jmbi.1993.1626
68. Schönian G, Mauricio I, Gramiccia M, Caňavate C, Boelaert M, Dujardin JC. 2008. Leishmaniases in the Mediterranean in the era of molecular epidemiology. Trends in Parasitology 24:135–142. doi:10.1016/j.pt.2007.12.006
69. Stamatakis A. 2014. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 30:1312–1313. doi:10.1093/bioinformatics/btu033
70. Stephens M, Smith NJ, Donnelly P. 2001. A new statistical method for haplotype reconstruction from population data. American Journal of Human Genetics 68:978–989. doi:10.1086/319501
71. Sundar S, Chakravarty J. 2015. An update on pharmacotherapy for leishmaniasis. Expert Opinion on Pharmacotherapy 16:237–252. doi:10.1517/14656566.2015.973850
72. Sundar S, Singh A, Rai M, Prajapati VK, Singh AK, Ostyn B, Boelaert M, Dujardin JC, Chakravarty J. 2012. Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use. Clinical Infectious Diseases 55:543–550. doi:10.1093/cid/cis474
73. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. 2011. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Molecular Biology and Evolution 28:2731–2739. doi:10.1093/molbev/msr121
74. Tennessen JA, Bigham AW, O’Connor TD, Fu W, Kenny EE, Gravel S, McGee S, Do R, Liu X, Jun G, Kang HM, Jordan D, Leal SM, Gabriel S, Rieder MJ, Abecasis G, Altshuler D, Nickerson DA, Boerwinkle E, Sunyaev S, Bustamante CD, Bamshad MJ, Akey JM, Broad GO, Seattle GO, NHLBI Exome Sequencing Project. 2012. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 337: 64–69. doi:10.1126/science.1219240
75. Thakur CP. 2007. A new strategy for elimination of kala-azar from rural Bihar. The Indian Journal of Medical Research 126:447–451.
76. Uzcategui NL, Zhou Y, Figarella K, Ye J, Mukhopadhyay R, Bhattacharjee H. 2008. Alteration in glycerol and metalloid permeability by a single mutation in the extracellular C-loop of Leishmania major aquaglyceroporin LmAQP1. Molecular Microbiology 70:1477–1486. doi:10.1111/j.1365-2958.2008.06494.x
77. Van Meirvenne N, Janssens PG, Magnus E. 1975. Antigenic variation in syringe passaged populations of Trypanosoma (Trypanozoon) brucei. 1. Rationalization of the experimental approach. Annales De La Société Belge De Médecine Tropicale 55:1–23.
78. Vanaerschot M, Decuypere S, Berg M, Roy S, Dujardin JC. 2013. Drug-resistant microorganisms with a higher fitness – can medicines boost pathogens? Critical Reviews in Microbiology 39:384–394. doi:10.3109/1040841X.2012.716818
79. Weisenfeld NI, Yin S, Sharpe T, Lau B, Hegarty R, Holmes L, Sogoloff B, Tabbaa D, Williams L, Russ C, Nusbaum C, Lander ES, MacCallum I, Jaffe DB. 2014. Comprehensive variation discovery in single human genomes. Nature Genetics 46:1350–1355. doi:10.1038/ng.3121
80. Wiese M. 1998. A mitogen-activated protein (MAP) kinase homologue of Leishmania mexicana is essential for parasite survival in the infected host. The EMBO Journal 17:2619–2628. doi:10.1093/emboj/17.9.2619
81. Zhang WW, Ramasamy G, McCall LI, Haydock A, Ranasinghe S, Abeygunasekara P, Sirimanna G, Wickremasinghe R, Myler P, Matlashewski G. 2014. Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain. PLoS Pathogens 10:e1004244. doi:10.1371/journal.ppat.1004244