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Published in: Malaria Journal 1/2016

Open Access 01-12-2016 | Research

Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines

Authors: Susana Campino, Ernest Diez Benavente, Samuel Assefa, Eloise Thompson, Laura G. Drought, Catherine J. Taylor, Zaria Gorvett, Celine K. Carret, Christian Flueck, Al C. Ivens, Dominic P. Kwiatkowski, Pietro Alano, David A. Baker, Taane G. Clark

Published in: Malaria Journal | Issue 1/2016

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Abstract

Background

Transmission of the malaria parasite Plasmodium falciparum from humans to the mosquito vector requires differentiation of a sub-population of asexual forms replicating within red blood cells into non-dividing male and female gametocytes. The nature of the molecular mechanism underlying this key differentiation event required for malaria transmission is not fully understood.

Methods

Whole genome sequencing was used to examine the genomic diversity of the gametocyte non-producing 3D7-derived lines F12 and A4. These lines were used in the recent detection of the PF3D7_1222600 locus (encoding PfAP2-G), which acts as a genetic master switch that triggers gametocyte development.

Results

The evolutionary changes from the 3D7 parental strain through its derivatives F12 (culture-passage derived cloned line) and A4 (transgenic cloned line) were identified. The genetic differences including the formation of chimeric var genes are presented.

Conclusion

A genomics resource is provided for the further study of gametocytogenesis or other phenotypes using these parasite lines.
Appendix
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Literature
1.
go back to reference WHO. World Malaria Report 2015. Geneva: World Health Organization; 2015. WHO. World Malaria Report 2015. Geneva: World Health Organization; 2015.
3.
go back to reference A-Elbasit IE, Elbashir MI, Khalil IF, Alifrangis M, Giha HA. The efficacy of sulfadoxine-pyrimethamine alone and in combination with chloroquine for malaria treatment in rural Eastern Sudan: the interrelation between resistance, age and gametocytogenesis. Trop Med Int Health. 2006;11:604–12.CrossRefPubMed A-Elbasit IE, Elbashir MI, Khalil IF, Alifrangis M, Giha HA. The efficacy of sulfadoxine-pyrimethamine alone and in combination with chloroquine for malaria treatment in rural Eastern Sudan: the interrelation between resistance, age and gametocytogenesis. Trop Med Int Health. 2006;11:604–12.CrossRefPubMed
4.
go back to reference Puta C, Manyando C. Enhanced gametocyte production in Fansidar-treated Plasmodium falciparum malaria patients: implications for malaria transmission control programmes. Trop Med Int Health. 1997;2:227–9.CrossRefPubMed Puta C, Manyando C. Enhanced gametocyte production in Fansidar-treated Plasmodium falciparum malaria patients: implications for malaria transmission control programmes. Trop Med Int Health. 1997;2:227–9.CrossRefPubMed
5.
go back to reference Williams JL. Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures. Am J Trop Med Hyg. 1999;60:7–13.PubMed Williams JL. Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures. Am J Trop Med Hyg. 1999;60:7–13.PubMed
6.
go back to reference Barnes KI, Little F, Mabuza A, Mngomezulu N, Govere J, Durrheim D, et al. Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria. J Infect Dis. 2008;197:1605–13.CrossRefPubMed Barnes KI, Little F, Mabuza A, Mngomezulu N, Govere J, Durrheim D, et al. Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria. J Infect Dis. 2008;197:1605–13.CrossRefPubMed
7.
go back to reference Trager W, Gill GS. Plasmodium falciparum gametocyte formation in vitro: its stimulation by phorbol diesters and by 8-bromo cyclic adenosine monophosphate. J Protozool. 1989;36:451–4.CrossRefPubMed Trager W, Gill GS. Plasmodium falciparum gametocyte formation in vitro: its stimulation by phorbol diesters and by 8-bromo cyclic adenosine monophosphate. J Protozool. 1989;36:451–4.CrossRefPubMed
8.
go back to reference Dyer M, Day K. Expression of Plasmodium falciparum trimeric G proteins and their involvement in switching to sexual development. Mol Biochem Parasitol. 2000;110:437–48.CrossRefPubMed Dyer M, Day K. Expression of Plasmodium falciparum trimeric G proteins and their involvement in switching to sexual development. Mol Biochem Parasitol. 2000;110:437–48.CrossRefPubMed
9.
go back to reference Day KP, Karamalis F, Thompson J, Barnes DA, Peterson C, Brown H, et al. Genes necessary for expression of a virulence determinant and for transmission of Plasmodium falciparum are located on a 0.3-megabase region of chromosome 9. Proc Natl Acad Sci USA. 1993;90:8292–6.CrossRefPubMedPubMedCentral Day KP, Karamalis F, Thompson J, Barnes DA, Peterson C, Brown H, et al. Genes necessary for expression of a virulence determinant and for transmission of Plasmodium falciparum are located on a 0.3-megabase region of chromosome 9. Proc Natl Acad Sci USA. 1993;90:8292–6.CrossRefPubMedPubMedCentral
10.
go back to reference Alano P, Roca L, Smith D, Read D, Carter R, Day K. Plasmodium falciparum: parasites defective in early stages of gametocytogenesis. Exp Parasitol. 1995;81:227–35.CrossRefPubMed Alano P, Roca L, Smith D, Read D, Carter R, Day K. Plasmodium falciparum: parasites defective in early stages of gametocytogenesis. Exp Parasitol. 1995;81:227–35.CrossRefPubMed
11.
go back to reference Eksi S, Morahan BJ, Haile Y, Furuya T, Jiang H, Ali O, et al. Plasmodium falciparum gametocyte development 1 (Pfgdv1) and gametocytogenesis early gene identification and commitment to sexual development. PLoS Pathog. 2012;8:e1002964.CrossRefPubMedPubMedCentral Eksi S, Morahan BJ, Haile Y, Furuya T, Jiang H, Ali O, et al. Plasmodium falciparum gametocyte development 1 (Pfgdv1) and gametocytogenesis early gene identification and commitment to sexual development. PLoS Pathog. 2012;8:e1002964.CrossRefPubMedPubMedCentral
12.
go back to reference Ikadai H, Shaw Saliba K, Kanzok SM, McLean KJ, Tanaka TQ, Cao J, et al. Transposon mutagenesis identifies genes essential for Plasmodium falciparum gametocytogenesis. Proc Natl Acad Sci U S A. 2013;110:E1676–84.CrossRefPubMedPubMedCentral Ikadai H, Shaw Saliba K, Kanzok SM, McLean KJ, Tanaka TQ, Cao J, et al. Transposon mutagenesis identifies genes essential for Plasmodium falciparum gametocytogenesis. Proc Natl Acad Sci U S A. 2013;110:E1676–84.CrossRefPubMedPubMedCentral
13.
go back to reference Kafsack BFC, Rovira-Graells N, Clark TG, Bancells C, Crowley VM, Campino SG, et al. A transcriptional switch underlies commitment to sexual development in malaria parasites. Nature. 2014;507:248–52.CrossRefPubMedPubMedCentral Kafsack BFC, Rovira-Graells N, Clark TG, Bancells C, Crowley VM, Campino SG, et al. A transcriptional switch underlies commitment to sexual development in malaria parasites. Nature. 2014;507:248–52.CrossRefPubMedPubMedCentral
14.
go back to reference Sinha A, Hughes KR, Modrzynska KK, Otto TD, Pfander C, Dickens NJ, et al. A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium. Nature. 2014;507:253–7.CrossRefPubMedPubMedCentral Sinha A, Hughes KR, Modrzynska KK, Otto TD, Pfander C, Dickens NJ, et al. A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium. Nature. 2014;507:253–7.CrossRefPubMedPubMedCentral
15.
go back to reference Silvestrini F, Bozdech Z, Lanfrancotti A, Di Giulio E, Bultrini E, Picci L, et al. Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum. Mol Biochem Parasitol. 2005;143:100–10.CrossRefPubMed Silvestrini F, Bozdech Z, Lanfrancotti A, Di Giulio E, Bultrini E, Picci L, et al. Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum. Mol Biochem Parasitol. 2005;143:100–10.CrossRefPubMed
16.
go back to reference Taylor CJ, McRobert L, Baker DA. Disruption of a Plasmodium falciparum cyclic nucleotide phosphodiesterase gene causes aberrant gametogenesis. Mol Microbiol. 2008;69:110–8.CrossRefPubMedPubMedCentral Taylor CJ, McRobert L, Baker DA. Disruption of a Plasmodium falciparum cyclic nucleotide phosphodiesterase gene causes aberrant gametogenesis. Mol Microbiol. 2008;69:110–8.CrossRefPubMedPubMedCentral
17.
go back to reference Claessens A, Hamilton WL, Kekre M, Otto TD, Faizullabhoy A, Rayner JC, et al. Generation of antigenic diversity in Plasmodium falciparum by structured rearrangement of Var genes during mitosis. PLoS Genet. 2014;10:e1004812.CrossRefPubMedPubMedCentral Claessens A, Hamilton WL, Kekre M, Otto TD, Faizullabhoy A, Rayner JC, et al. Generation of antigenic diversity in Plasmodium falciparum by structured rearrangement of Var genes during mitosis. PLoS Genet. 2014;10:e1004812.CrossRefPubMedPubMedCentral
18.
go back to reference Bopp SER, Manary MJ, Bright AT, Johnston GL, Dharia NV, Luna FL, et al. Mitotic evolution of Plasmodium falciparum shows a stable core genome but recombination in antigen families. PLoS Genet. 2013;9:e1003293.CrossRefPubMedPubMedCentral Bopp SER, Manary MJ, Bright AT, Johnston GL, Dharia NV, Luna FL, et al. Mitotic evolution of Plasmodium falciparum shows a stable core genome but recombination in antigen families. PLoS Genet. 2013;9:e1003293.CrossRefPubMedPubMedCentral
19.
go back to reference Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002;419:498–511.CrossRefPubMed Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002;419:498–511.CrossRefPubMed
20.
go back to reference Miotto O, Amato R, Ashley EA, MacInnis B, Almagro-Garcia J, Amaratunga C, et al. Genetic architecture of artemisinin-resistant Plasmodium falciparum. Nat Genet. 2015;47:226–34.CrossRefPubMedPubMedCentral Miotto O, Amato R, Ashley EA, MacInnis B, Almagro-Garcia J, Amaratunga C, et al. Genetic architecture of artemisinin-resistant Plasmodium falciparum. Nat Genet. 2015;47:226–34.CrossRefPubMedPubMedCentral
21.
go back to reference Manske M, Miotto O, Campino S, Auburn S, Almagro-Garcia J, Maslen G, et al. Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature. 2012;487:375–9.CrossRefPubMedPubMedCentral Manske M, Miotto O, Campino S, Auburn S, Almagro-Garcia J, Maslen G, et al. Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature. 2012;487:375–9.CrossRefPubMedPubMedCentral
22.
go back to reference Ocholla H, Preston MD, Mipando M, Jensen ATR, Campino S, MacInnis B, et al. Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates. J Infect Dis. 2014;210:1991–2000.CrossRefPubMedPubMedCentral Ocholla H, Preston MD, Mipando M, Jensen ATR, Campino S, MacInnis B, et al. Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates. J Infect Dis. 2014;210:1991–2000.CrossRefPubMedPubMedCentral
23.
go back to reference Auburn S, Campino S, Clark TG, Djimde AA, Zongo I, Pinches R, et al. An effective method to purify Plasmodium falciparum DNA directly from clinical blood samples for whole genome high-throughput sequencing. PLoS One. 2011;6:4–11.CrossRef Auburn S, Campino S, Clark TG, Djimde AA, Zongo I, Pinches R, et al. An effective method to purify Plasmodium falciparum DNA directly from clinical blood samples for whole genome high-throughput sequencing. PLoS One. 2011;6:4–11.CrossRef
24.
go back to reference Preston MD, Assefa SA, Ocholla H, Sutherland CJ, Borrmann S, Nzila A, et al. PlasmoView: a web-based resource to visualise global Plasmodium falciparum genomic variation. J Infect Dis. 2014;209:1808–15.CrossRefPubMedPubMedCentral Preston MD, Assefa SA, Ocholla H, Sutherland CJ, Borrmann S, Nzila A, et al. PlasmoView: a web-based resource to visualise global Plasmodium falciparum genomic variation. J Infect Dis. 2014;209:1808–15.CrossRefPubMedPubMedCentral
26.
go back to reference Rausch T, Zichner T, Schlattl A, Stütz AM, Benes V, Korbel JO. DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics. 2012;28:i333–9.CrossRefPubMedPubMedCentral Rausch T, Zichner T, Schlattl A, Stütz AM, Benes V, Korbel JO. DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics. 2012;28:i333–9.CrossRefPubMedPubMedCentral
28.
go back to reference Samad H, Coll F, Preston MD, Ocholla H, Fairhurst RM, Clark TG. Imputation-based population genetics analysis of Plasmodium falciparum malaria parasites. PLoS Genet. 2015;11:e1005131.CrossRefPubMedPubMedCentral Samad H, Coll F, Preston MD, Ocholla H, Fairhurst RM, Clark TG. Imputation-based population genetics analysis of Plasmodium falciparum malaria parasites. PLoS Genet. 2015;11:e1005131.CrossRefPubMedPubMedCentral
29.
go back to reference Calderwood MS, Gannoun-Zaki L, Wellems TE, Deitsch KW. Plasmodium falciparum var genes are regulated by two regions with separate promoters, one upstream of the coding region and a second within the intron. J Biol Chem. 2003;278:34125–32.CrossRefPubMed Calderwood MS, Gannoun-Zaki L, Wellems TE, Deitsch KW. Plasmodium falciparum var genes are regulated by two regions with separate promoters, one upstream of the coding region and a second within the intron. J Biol Chem. 2003;278:34125–32.CrossRefPubMed
30.
go back to reference Avraham I, Schreier J, Dzikowski R. Insulator-like pairing elements regulate silencing and mutually exclusive expression in the malaria parasite. Plasmodium falciparum. 2012;109:E3678–86. Avraham I, Schreier J, Dzikowski R. Insulator-like pairing elements regulate silencing and mutually exclusive expression in the malaria parasite. Plasmodium falciparum. 2012;109:E3678–86.
31.
go back to reference Brancucci NMB, Bertschi NL, Zhu L, Niederwieser I, Chin WH, Wampfler R, et al. Heterochromatin protein 1 secures survival and transmission of malaria parasites. Cell Host Microbe. 2014;16:165–76.CrossRefPubMed Brancucci NMB, Bertschi NL, Zhu L, Niederwieser I, Chin WH, Wampfler R, et al. Heterochromatin protein 1 secures survival and transmission of malaria parasites. Cell Host Microbe. 2014;16:165–76.CrossRefPubMed
32.
go back to reference Coleman BI, Skillman KM, Jiang RHY, Childs LM, Altenhofen LM, Ganter M, et al. A Plasmodium falciparum histone deacetylase regulates antigenic variation and gametocyte conversion. Cell Host Microbe. 2014;16:177–86.CrossRefPubMedPubMedCentral Coleman BI, Skillman KM, Jiang RHY, Childs LM, Altenhofen LM, Ganter M, et al. A Plasmodium falciparum histone deacetylase regulates antigenic variation and gametocyte conversion. Cell Host Microbe. 2014;16:177–86.CrossRefPubMedPubMedCentral
34.
go back to reference Taylor CJ. The role of two cyclic nucleotide phosphodiesterases in the sexual development of Plasmodium falciparum and Plasmodium berghei. PhD Thesis. University of London; 2007. Taylor CJ. The role of two cyclic nucleotide phosphodiesterases in the sexual development of Plasmodium falciparum and Plasmodium berghei. PhD Thesis. University of London; 2007.
35.
go back to reference Duraisingh MT, Triglia T, Cowman AF. Negative selection of Plasmodium falciparum reveals targeted gene deletion by double crossover recombination. Int J Parasitol. 2002;32:81–9.CrossRefPubMed Duraisingh MT, Triglia T, Cowman AF. Negative selection of Plasmodium falciparum reveals targeted gene deletion by double crossover recombination. Int J Parasitol. 2002;32:81–9.CrossRefPubMed
36.
go back to reference Young JA, Fivelman QL, Blair PL, de la Vega P, Le Roch KG, Zhou Y, et al. The Plasmodium falciparum sexual development transcriptome: a microarray analysis using ontology-based pattern identification. Mol Biochem Parasitol. 2005;143:67–79.CrossRefPubMed Young JA, Fivelman QL, Blair PL, de la Vega P, Le Roch KG, Zhou Y, et al. The Plasmodium falciparum sexual development transcriptome: a microarray analysis using ontology-based pattern identification. Mol Biochem Parasitol. 2005;143:67–79.CrossRefPubMed
37.
go back to reference Campbell TL, De Silva EK, Olszewski KL, Elemento O, Llinás M. Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite. PLoS Pathog. 2010;6:e1001165.CrossRefPubMedPubMedCentral Campbell TL, De Silva EK, Olszewski KL, Elemento O, Llinás M. Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite. PLoS Pathog. 2010;6:e1001165.CrossRefPubMedPubMedCentral
38.
go back to reference López-Barragán MJ, Lemieux J, Quiñones M, Williamson KC, Molina-Cruz A, Cui K, et al. Directional gene expression and antisense transcripts in sexual and asexual stages of Plasmodium falciparum. BMC Genomics. 2011;12:587.CrossRefPubMedPubMedCentral López-Barragán MJ, Lemieux J, Quiñones M, Williamson KC, Molina-Cruz A, Cui K, et al. Directional gene expression and antisense transcripts in sexual and asexual stages of Plasmodium falciparum. BMC Genomics. 2011;12:587.CrossRefPubMedPubMedCentral
Metadata
Title
Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines
Authors
Susana Campino
Ernest Diez Benavente
Samuel Assefa
Eloise Thompson
Laura G. Drought
Catherine J. Taylor
Zaria Gorvett
Celine K. Carret
Christian Flueck
Al C. Ivens
Dominic P. Kwiatkowski
Pietro Alano
David A. Baker
Taane G. Clark
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2016
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-016-1254-1

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