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Bottlenecks and the Maintenance of Minor Genotypes during the Life Cycle of


African trypanosomes are digenetic parasites that undergo part of their developmental cycle in mammals and part in tsetse flies. We established a novel technique to monitor the population dynamics of Trypanosoma brucei throughout its life cycle while minimising the confounding factors of strain differences or variation in fitness. Clones derived from a single trypanosome were tagged with short synthetic DNA sequences in a non-transcribed region of the genome. Infections were initiated with mixtures of tagged parasites and a combination of polymerase chain reaction and deep sequencing were used to monitor the composition of populations throughout the life cycle. This revealed that a minimum of several hundred parasites survived transmission from a tsetse fly to a mouse, or vice versa, and contributed to the infection in the new host. In contrast, the parasites experienced a pronounced bottleneck during differentiation and migration from the midgut to the salivary glands of tsetse. In two cases a single tag accounted for ≥99% of the population in the glands, although minor tags could be also detected. Minor tags were transmitted to mice together with the dominant tag(s), persisted during a chronic infection, and survived transmission to a new insect host. An important outcome of the bottleneck within the tsetse is that rare variants can be amplified in individual flies and disseminated by them. This is compatible with the epidemic population structure of T. brucei, in which clonal expansion of a few genotypes in a region occurs against a background of frequent recombination between strains.


Vyšlo v časopise: Bottlenecks and the Maintenance of Minor Genotypes during the Life Cycle of. PLoS Pathog 6(7): e32767. doi:10.1371/journal.ppat.1001023
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001023

Souhrn

African trypanosomes are digenetic parasites that undergo part of their developmental cycle in mammals and part in tsetse flies. We established a novel technique to monitor the population dynamics of Trypanosoma brucei throughout its life cycle while minimising the confounding factors of strain differences or variation in fitness. Clones derived from a single trypanosome were tagged with short synthetic DNA sequences in a non-transcribed region of the genome. Infections were initiated with mixtures of tagged parasites and a combination of polymerase chain reaction and deep sequencing were used to monitor the composition of populations throughout the life cycle. This revealed that a minimum of several hundred parasites survived transmission from a tsetse fly to a mouse, or vice versa, and contributed to the infection in the new host. In contrast, the parasites experienced a pronounced bottleneck during differentiation and migration from the midgut to the salivary glands of tsetse. In two cases a single tag accounted for ≥99% of the population in the glands, although minor tags could be also detected. Minor tags were transmitted to mice together with the dominant tag(s), persisted during a chronic infection, and survived transmission to a new insect host. An important outcome of the bottleneck within the tsetse is that rare variants can be amplified in individual flies and disseminated by them. This is compatible with the epidemic population structure of T. brucei, in which clonal expansion of a few genotypes in a region occurs against a background of frequent recombination between strains.


Zdroje

1. BartonN

CharlesworthB

1984 Genetic Revolutions, Founder Effects, and Speciation. Annual Review of Ecology and Systematics 15 133.164

2. RichSM

LichtMC

HudsonRR

AyalaFJ

1998 Malaria's Eve: evidence of a recent population bottleneck throughout the world populations of Plasmodium falciparum. Proc Natl Acad Sci U S A 95 4425 4430

3. MackinnonMJ

BellA

ReadAF

2005 The effects of mosquito transmission and population bottlenecking on virulence, multiplication rate and rosetting in rodent malaria. Int J Parasitol 35 145 153

4. NeiM

MaruyamaT

ChakrabortyR

1975 The bottleneck effect and genetic variability in populations. Evolution 29 1 10

5. RoditiI

LehaneMJ

2008 Interactions between trypanosomes and tsetse flies. Curr Opin Microbiol 11 345 351

6. Van Den AbbeeleJ

ClaesY

van BockstaeleD

Le RayD

CoosemansM

1999 Tryanosoma brucei spp. development in the tsetse fly: characterization of the post-mesocyclic stages in the foregut and proboscis. Parasitology 118 469 478

7. MolooSK

KabataJM

SabwaCL

1994 A study on the maturation of procyclic Trypanosoma brucei brucei in Glossina morsitans centralis and G. brevipalpis. Med Vet Entomol 8 369 374

8. SharmaR

PeacockL

GluenzE

GullK

GibsonW

2008 Asymmetric cell division as a route to reduction in cell length and change in cell morphology in trypanosomes. Protist 159 137 151

9. BruceD

HamertonAE

BatemanHR

MackieFP

1911 Further researches on the development of Trypanosoma gambiense in Glossina palpalis. Proc Roy Soc B 83 513 527

10. HarmsenR

1973 The nature of the establishment barrier for Trypanosoma brucei in the gut of Glossina pallidipes. Trans R Soc Trop Med Hyg 67 364 373

11. PeacockL

FerrisV

BaileyM

GibsonW

2007 Dynamics of infection and competition between two strains of Trypanosoma brucei brucei in the tsetse fly observed using fluorescent markers. Kinetoplastid Biol Dis 6 4

12. GibsonW

PeacockL

FerrisV

WilliamsK

BaileyM

2008 The use of yellow fluorescent hybrids to indicate mating in Trypanosoma brucei. Parasit Vectors 1 4

13. VickermanK

1985 Developmental cycles and biology of pathogenic trypanosomes. Br Med Bull 41 105 114

14. FairbairnH

BurttE

1946 The infectivity to man of a strain of Trypanosoma rhodesiense transmitted cyclically by Glossina morsitans through sheep and antelope: evidence that man requires a minimum infective dose of metacyclic trypanosomes. Annals of Tropical Medicine and Parasitology 40 270 313

15. BrunR

JenniL

1987 Human serum resistance of metacyclic forms of Trypanosoma brucei brucei, T. brucei rhodesiense and T. brucei gambiense. Parasitol Res 73 218 223

16. VickermanK

TetleyL

HendryKA

TurnerCM

1988 Biology of African trypanosomes in the tsetse fly. Biol Cell 64 109 119

17. MaudlinI

WelburnSC

1989 A single trypanosome is sufficient to infect a tsetse fly. Ann Trop Med Parasitol 83 431 433

18. ThuitaJK

KagiraJM

MwangangiD

MatovuE

TurnerCM

2008 Trypanosoma brucei rhodesiense Transmitted by a Single Tsetse Fly Bite in Vervet Monkeys as a Model of Human African Trypanosomiasis. PLoS Negl Trop Dis 2 e238

19. GingrichJB

WardRA

MackenLM

EsserKM

1981 Some phenomena associated with the development of Trypanosoma brucei rhodesiense infections in the tsetse fly, Glossina morsitans. Am J Trop Med Hyg 30 570 574

20. EbertD

1998 Experimental evolution of parasites. Science 282 1432 1435

21. RueppS

FurgerA

KurathU

RenggliCK

HemphillA

1997 Survival of Trypanosoma brucei in the tsetse fly is enhanced by the expression of specific forms of procyclin. J Cell Biol 137 1369 1379

22. VassellaE

OberleM

UrwylerS

RenggliCK

StuderE

2009 Major surface glycoproteins of insect forms of Trypanosoma brucei are not essential for cyclical transmission by tsetse. PLoS One 4 e4493

23. SimpsonEH

1949 Measurement of diversity. Nature 163 688

24. AitchesonN

TalbotS

ShapiroJ

HughesK

AdkinC

2005 VSG switching in Trypanosoma brucei: antigenic variation analysed using RNAi in the absence of immune selection. Mol Microbiol 57 1608 1622

25. MorrisonLJ

MajiwaP

ReadAF

BarryJD

2005 Probabilistic order in antigenic variation of Trypanosoma brucei. Int J Parasitol

26. LythgoeKA

MorrisonLJ

ReadAF

BarryJD

2007 Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation. Proc Natl Acad Sci U S A 104 8095 8100

27. CapbernA

GiroudC

BaltzT

MatternP

1977 Trypanosoma equiperdum: antigenic variations in experimental trypanosomiasis of rabbits. Exp Parasitol 42 6 13

28. WoottonJC

FengX

FerdigMT

CooperRA

MuJ

2002 Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum. Nature 418 320 323

29. de RoodeJC

CulletonR

BellAS

ReadAF

2004 Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections. Malar J 3 33

30. MacLeodA

TweedieA

WelburnSC

MaudlinI

TurnerCM

2000 Minisatellite marker analysis of Trypanosoma brucei: reconciliation of clonal, panmictic, and epidemic population genetic structures. Proc Natl Acad Sci U S A 97 13442 13447

31. StevensJR

Mathieu DaudeF

McNamaraJJ

MizenVH

NzilaA

1994 Mixed populations of Trypanosoma brucei in wild Glossina palpalis palpalis. Trop Med Parasitol 45 313 318

32. MacLeodA

TurnerCM

TaitA

1999 A high level of mixed Trypanosoma brucei infections in tsetse flies detected by three hypervariable minisatellites. Mol Biochem Parasitol 102 237 248

33. BalmerO

CacconeA

2008 Multiple-strain infections of Trypanosoma brucei across Africa. Acta Trop 107 275 279

34. BalmerO

StearnsSC

SchotzauA

BrunR

2009 Intraspecific competition between co-infecting parasite strains enhances host survival in African trypanosomes. Ecology 90 3367 3378

35. TaitA

1980 Evidence for diploidy and mating in trypanosomes. Nature 287 536 538

36. JenniL

MartiS

SchweizerJ

BetschartB

Le PageRW

1986 Hybrid formation between African trypanosomes during cyclical transmission. Nature 322 173 175

37. Le RayD

BarryJD

EastonC

VickermanK

1977 First tsetse fly transmission of the “AnTat” serodeme of Trypanosoma brucei. Ann Soc Belg Med Trop 57 369 381

38. BrunR

SchoenenbergerM

1979 Cultivation and in vitro cloning of procyclic culture forms of Trypanosoma brucei in a semi-defined medium. Acta Tropica 36 289 292

39. BrunR

SchoenenbergerM

1981 Stimulating effect of citrate and cis-aconitate on the transformation of Trypanosoma brucei bloodstream forms to procyclic forms in vitro. Z Parasitenkd 66 17 24

40. VassellaE

Den AbbeeleJV

BütikoferP

RenggliCK

FurgerA

2000 A major surface glycoprotein of Trypanosoma brucei is expressed transiently during development and can be regulated post- transcriptionally by glycerol or hypoxia. Genes Dev 14 615 626

41. ThomasRK

NickersonE

SimonsJF

JannePA

TengsT

2006 Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing. Nat Med 12 852 855

42. MarguliesM

EgholmM

AltmanWE

AttiyaS

BaderJS

2005 Genome sequencing in microfabricated high-density picolitre reactors. Nature 437 376 380

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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