Meiosis and Haploid Gametes in the Pathogen Trypanosoma brucei

Abstract

SummaryIn eukaryote pathogens, sex is an important driving force in spreading genes for drug resistance, pathogenicity, and virulence [1]. For the parasitic trypanosomes that cause African sleeping sickness, mating occurs during transmission by the tsetse vector [2, 3] and involves meiosis [4], but haploid gametes have not yet been identified. Here, we show that meiosis is a normal part of development in the insect salivary glands for all subspecies of Trypanosoma brucei, including the human pathogens. By observing insect-derived trypanosomes during the window of peak expression of meiosis-specific genes, we identified promastigote-like (PL) cells that interacted with each other via their flagella and underwent fusion, as visualized by the mixing of cytoplasmic red and green fluorescent proteins. PL cells had a short, wide body, a very long anterior flagellum, and either one or two kinetoplasts, but only the anterior kinetoplast was associated with the flagellum. Measurement of nuclear DNA contents showed that PL cells were haploid relative to diploid metacyclics. Trypanosomes are among the earliest diverging eukaryotes, and our results support the hypothesis that meiosis and sexual reproduction are ubiquitous in eukaryotes and likely to have been early innovations [5].

Insect Stage-Specific Receptor Adenylate Cyclases Are Localized to Distinct Subdomains of the Trypanosoma brucei Flagellar Membrane

“…There is also a precedent for flagellum tip attachment triggering cellular differentiation in the protist Chlamydomonas reinhardtii, whereby flagellum tip adhesion between two gametes triggers a cAMP signaling cascade resulting in gamete fusion (69,70,78). Recent ex vivo reconstruction of the T. brucei mating cycle identified gamete-like cells that interact via their flagella prior to fusion (79), raising the intriguing possibility that flagellum-dependent interactions may be part of the T. brucei mating cycle. The flagellum functions in mechanosensation in other protists (80,81) and may therefore function in contactmediated signaling in T. brucei.…”

Sex is a ubiquitous, ancient, and inherent attribute of eukaryotic life

“…Numerous examples illustrate how little we know about the actual life of eukaryotic microorganisms, even those studied for a very long time. The kinetoplastid protozoan Trypanosoma brucei (Euglenozoa), a causative agent of sleeping sickness, is one of the beststudied protist species, yet meiosis and gametes were only detected very recently (10,11). Although meiosis has thus far been considered to be very rare in trypanosomes, it may actually be more frequent, as both intraclonal and interclonal mating has been documented (10).…”

Neglected Tropical Diseases in the Post-Genomic Era

“…Advances in our understanding of NTD pathogens have been difficult owing to several financial, technical, and biological obstacles, including a lack of appropriate in vitro/in vivo culture systems [6,7], the inherent inaccessibility or scarcity of some of the developmental forms of parasites [8], or the existence of highly structured populations (i.e., populations composed of multiple 'strains' or 'types' showing genome size variation and extensive karyotype polymorphism) within species displaying asexual, or rarely sexual, reproduction [9]. The past decade, however, has witnessed major achievements in NTD pathogen research fueled primarily by recent advances in highthroughput technologies and the introduction of powerful molecular, cellular, and genetic tools.…”

“…All are strict diploid organisms, with sexual recombination occurring in the salivary glands of tsetse fly vectors [8]. Sexual exchange proceeds under a classical Mendelian segregation of alleles, supporting both cross-and self-fertilization [44].…”

“…In both cases, it was suggested to be mediated by a process that includes fusion of parental cells, homologous recombination, loss of alleles, and uniparental inheritance of kinetoplast DNA [54,59]. As for T. brucei, mating in Leishmania must be considered a non-obligatory part of the life cycle, because the majority of coinfected insect vectors failed to yield a hybrid but were still permissive to the development of mature, humaninfectious forms [8,60].…”