Evolutionary genetics of tsetse flies, its parasites and symbionts

Human African Trypanosomiasis (HAT) (a.k.a. African sleeping sickness) kills thousands of people each year in sub-Saharan Africa. The Animal African trypanososmias (AAT) or Nagana kills cattle and other livestock, thus impacts African economic in significant ways. Both disease are caused by the African trypanosomes in the Trypanosoma brucei complex and are transmitted by tsetse flies species within the genus Glossina. HAT transmission is complex; it requires mammalian and invertebrate hosts and involves domestic and wild reservoirs. Our general goal is to understand the spatial and temporal patterns of genetic differentiation of the various members of this complex disease transmission which include the Glossina flies and its symbionts and parasites: Trypanosoma, Wolbachia, Sodalis, Spiroplasma, and Wigglesworthia. The interest in the symbionts is fueled by the fact that they impact the fly fitness and/or their capacity to transmit Trypanosomes. The work focuses in East Africa, in particular Uganda, Kenya and Tanzania. Uganda is of particular interest because only in this country the two human infective parasites co-occur and more important their range is about to merge, posing significant new challenge to the monitoring, control, and prevention of the disease. We have been using microsatellite and mitochondrial DNA (mtDNA) data together with population genetic and phylogeographic approaches to understand patterns of spatial and temporal of the vector, and its parasite and symbionts, examining their coevolution and evaluating the ecological and environmental processes that impact they distribution, and providing baseline data to the agencies that monitor and control both diseases in the endemic countries.

locals

For the past 3-5 years we have supplemented the microsatellite and mtDNA data with whole genome analyses, including the use of ddRAD Seq and whole genome data to look at Glossina

fuscipes genome wide variation. Similarly, we are using Illumina and PacBio data to carry out population genomic analyses of multiple Trypanosoma brucei strains across Africa.  We are using evolutionary principles and approaches to evaluate their evolutionary history and thus provide information to better define their taxonomy, so far based on the their virulence towards humans and their geographic location, as well as to gain insights on the relation between strain identity and emergence of new disease foci. We also produced the first de novo assembly of Trypanosoma brucei rhodesiense, the parasite responsible for the acute form of HAT, and compared it to the available genomes for the other Trypanosma brucei genomes from the non-human infective strains (T. brucei brucei) and the ones responsible for the chronic form of sleeping sickness (T. brucei gambienese). Using evolutionary approaches we are also working on understanding the dynamics of re-infection in human patients that were treated but then relapsed, to evaluate if the re-emergene of the disease is due to the same strain or to different infections.  Future works on vectors, parasite, and symbionts continues in these general directions expanding the focus from Uganda and the Lake Victoria region to include the analyses of Glossina pallidipes population in Kenya and Tanzania and the comparative analyses of genetic polymorphisms in Kenyan isolates of Trypanosoma evansi, a strain likely derived from Trypanosoma brucei brucei, whose ability to be transmitted by non-tsetse flies, enabled it to expand outside Africa. We are also been involved in building capacity for Trypanosomiasis research in East Africa by training a cadre of young scientists at various stages of their career (graduate students, postdoctoral associates, faculty members) from Uganda, Kenya, and Tanzania that over the past 10 years have received training in our laboratory or participated to in country workshops we helped organized.

Collaborators:

EEB postdocs: Jon Beadell, Beckie Symula, Mark Sistrom (past); Gus Dunn, Joshua Richardson, Andrea Gloria-Soria, Norah Saarman (present).

EEB graduate students: Oliver Balmer

Yale undergraduates: Alexis Halyard

EEB Research Assistants: Chaz Hyseni (past), Kirstin Dion (present)

Yale Faculty: Serap Aksoy, Alison Galvani, John Carlson

Uganda-Kenya-Tanzania graduate students: Patrick Abila, Richard Echodu, Rosemary Bateta, Oliver Kijanga (past), Robert Opiro, Winnie Okeyo, Christine Mujonia (present)

Non Yale faculty main collaborators: Anna Malacrida (University of Pavia), Loyce Okedi, Elizabeth Opyo, Richard Echodu (Uganda); Grace Murilla, Johnson Ouma, Paul Mireji (Kenya); Imna Malele (Tanzania); Martin Donnelly (Liverpool, England), Wendy Gibson (England); Oliver Balmer and Pascal Maeser (Switzerland); Philippe Buscher (Belgium).