Network scientists help to map parasite genome responsible for the sexually transmitted human infection, trichomoniasis.

01 February 2007

Dr Jacqui Upcroft and Prof. Peter Upcroft (pictured above), parasitologists from the Queensland Institute of Medical Research (QIMR), and their PhD student, Rebecca Dunne, are part of a group of 64 researchers worldwide who have recently published "Draft Genome Sequence of the Sexually Transmitted Pathogen Trichomonas vaginalis" in Science (Vol 315 12 January 2007 www.sciencemag.org).

Trichomonas vaginalis is a flagellated protist that causes trichomoniasis, a common but often overlooked sexually transmitted human infection with approximately 170 million cases worldwide. The extracellular parasite resides in the urogenital tract of both sexes. Acute infections are associated with pelvic inflammatory disease, increased risk of HIV-1 infection and adverse pregnancy outcomes.

Jane Carlton, of The Institute for Genomic Research (TIGR) and now at New York University School of Medicine, was the leader of this very successful project, in collaboration with Patricia Johnson, University of California, Los Angeles and with funding from the U.S. National Institutes of Health. Additionally, the Trichomonas research community collaborated together over the past 2 years to help analyze the T. vaginalis genome data. Each research group was responsible for different aspects of the analysis and everyone shared their data.

The QIMR researchers played a dual role in mapping the T. vaginalis genome: they were involved in analyzing the proteins involved in drug resistance to metronidazole in T. vaginalis, taking advantage of their 20+ years of experience on the same subject in another anaerobic protist, Giardia; and they also used pulse field gels to separate chromosomes to genotype for preliminary mapping.

"Trichomonas vaginalis is very difficult to map" Jacqui said, adding that, "CC Wang postulated many years ago that it has a very large genome but this idea was initially shunned by the parasitological world. However, we soon realised that we were either looking at something very unusual or something very large - and it turned out to be large. CC was right!" The assembly size of the T. vaginalis genome is estimated at 160Mb and the research group identified a core set of 60,000 protein-coding genes endowing T. vaginalis with one of the highest coding capacities among eukaryotes.

Jacqui says that, "T. vaginalis parasite has no business being what it is." It appears that T. vaginalis genome expansion may have occurred when the parasite moved from a gut to a urogenital tract environment, in comparison to the oral parasite, Trichomonas tenax, which doesn’t appear to have the same repeated genome and is likely smaller in cell size.

Why so large? The T. vaginalis genome has lots of repeated elements: at least 65% of it is repetitive and analysis of the large gene families shows there are more than 900 protein kinases, but that they are not involved in signalling, and more than 650 in the BspA-like gene family. The size of the genome and the volume of the typical T. vaginalis cell are positively correlated. This large cell size may be adaptive; T. vaginalis is a highly predatory parasite that phagocytoses bacteria, vaginal epithelial cells, and host erythrocytes and is itself ingested by macrophages. The group speculate that given these interactions, an increase in cell size could have been selected for to augment the parasite’s phagocytosis of bacteria and to reduce its own phagocytosis by host cells. Increased surface area may confer advantages for colonisation of vaginal mucosa.

The Trichomonas vaginalis genome consortium has at least two remaining burning ambitions: to secure further funding to sequence another Trichomonas (for valuable comparative studies); and to use the information from the genome to develop new therapies and novel methods for diagnosis.

Jacqui and Peter have been researchers at QIMR for the past 25 years and have made a huge contribution to parasitology research worldwide, culminating in their recent collaborations to sequence the Trichomonas vaginalis genome. Peter was a founding molecular biologist and developed the technique to transfect genes into viruses. When Jacqui was first working as a post doctoral fellow at Harvard Medical School she was purifying restriction enzymes from scratch! We wish Jacqui and Peter all the best for the future and hope to see more news from their lab this year.