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The evolution of gene content in parasitic protozoa

Final Report Summary - EVOGCPROTO (The evolution of gene content in parasitic protozoa)

Protozoan parasites impose a high burden on human health, particularly in developing countries and among immunocompromised individuals. For example, Trypanosoma and Leishmania cause African sleeping sickness, Chagas disease, and Leishmaniasis, which together cause over 60,000 deaths annually (World Health Organisation Fact Sheet #340; WHO 2010 report “Control of the leishmaniases”). Moreover, opportunistic protozoan diseases such as Cryptosporidiosis and Microsporidiosis have been increasing in step with the spread of the AIDS pandemic (Pieniazek et al. 1999 Emerg Inf Dis; 2006 WHO report “Water Recreation and Disease: Plausibility of Associated Infections”). Despite their importance for human health, major unanswered questions about the basic biology of protozoan parasites remain, and these gaps in knowledge hamper efforts to develop effective new therapies. In this project, I have been investigating the genomes of important human protozoan parasites to better understand how they have evolved from their free-living ancestors and to gain new insights into how they manipulate their hosts.
One of the most interesting results of my analyses has been the discovery that parasite genome evolution is much more dynamic than previously appreciated. In particular, the drastic reduction in genome size and loss of widely conserved genes observed for microsporidian parasites has, to a considerable extent, been balanced by the evolution of new, parasite-specific gene families (see Figure). Some of these families are found in different lineages of Microsporidia that infect a wide range of eukaryotic hosts, suggesting that they might play important general roles in the lifecycle of these important protozoan parasites. Consistent with that prediction, our transcriptomic analyses of these parasites indicated that parasite-specific genes are consistently among the most highly expressed genes during the spore and vegetative stages, highlighting these genes as key players in microsporidian biology. In addition, my computational analyses led to the identification of a number of new genes which these eukaryotic parasites have acquired by horizontal gene transfer from Bacteria; these also represent key candidates for future investigation of parasite lifecycle and mechanisms of pathogenicity.

Figure (see attachment): My work has revealed that reductive genome evolution in the Microsporidia, a group of intracellular fungal parasites, involved not only a massive loss of genes in the common ancestor of the group, but also subsequent lineage-specific innovation of new gene families, some of which may be involved in pathogenesis (Nakjang, Williams et al. 2013 Genome Biol Evol).

The work I have performed during my time as a Marie Curie Fellow has directly led to seven published papers (including one each in Nature and Current Biology, two of the most prestigious scientific journals), with several additional manuscripts currently in preparation. In addition, my fellowship has led to the production of several publicly available datasets – including one of parasite-specific gene families - which will enable other researchers to build on my work in dissecting the lifecycle and mechanisms of pathogenicity in these important eukaryotic parasites.

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