EVOGCPROTO

The evolution of gene content in parasitic protozoa

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 Obiettivo del progetto (Objective)

'Protozoan parasites from diverse evolutionary lineages including Trypanosoma and Leishmania, Giardia, Entamoeba, Plasmodium and the microsporidia have a major impact on human health, especially in developing countries and among immunocompromised individuals. During their evolution as parasites these organisms can both lose pathways if they can steal host metabolites and gain genes that may help them to manipulate their hosts. It is this balance of genome reduction and genome expansion, and the potential consequences for parasites and their eukaryotic hosts, that I will investigate in my project. Although the genome evolution of bacterial pathogens is relatively well studied, much less is known about how eukaryotic parasites - which are much more similar to their hosts - evolve at the genomic level. A sophisticated analytical approach will be used to compare genome reduction and expansion events in different groups of parasitic eukaryotes and their free-living relatives, to identify lineage specific and common evolutionary features. This framework will be used to identify and characterize new, parasite-specific protein families that may be involved in pathogenesis and, as an important part of my training, I will collaborate with bench scientists in the host lab to test these hypotheses. By identifying the gene families that are gained and lost during the evolution of parasitic protozoa, I will identify cases when bacteria and eukaryotes evolve in similar and different ways and hence gain insight into how parasites evolve more generally. Moreover, since parasites may lose genes that are strongly conserved among free-living model organisms, they also represent “natural experiments” for understanding which features of eukaryotic cells are essential and which are lineage specific elaborations. As a test case to explore this principle I will investigate the evolution and conservation of proteins involved in a fundamentally important eukaryotic pathway - the cell cycle.'

Introduzione (Teaser)

Parasites are able to control the behaviour and physiology of their hosts to best suit their lifestyle. An EU-funded project has looked at how the genetics of parasites with human hosts has changed through evolution to achieve this manipulation.

Descrizione progetto (Article)

Single-celled, eukaryotic parasites are a major threat to human health, particularly in developing countries and immunocompromised individuals. A diverse group, these include Trypanosoma (causing sleeping sickness), Leishmania spread through sandfly bites, Entamoeba causing dysentery, and the large phylum of over 1,000 species, the Microsporidia (Microspora).

During their evolution, these parasites have acquired new genes to help in their ability to manipulate the host and, at the same time, have lost many others. The project 'The evolution of gene content in parasitic protozoa' (EVOGCPROTO) has investigated, with sophisticated genomic and proteomic techniques, this expansion and reduction of eukaryotic parasitic genomes.

The researchers identified whole gene families that were gained and lost together with their source and so were able to identify those gene groups involved in pathogenesis. They also gained insight into when and how bacterial and eukaryotic parasites evolved in similar ways, a window to a more general understanding of parasite evolution from a free-living lifestyle.

Results of proteomic analysis revealed that genome evolution is very dynamic and there has been a drastic reduction in microsporidian genome size accompanied by the evolution of new, parasite-specific gene families. Some of these gene groups are found in other microsporidians that infect a wide range of hosts, indicating that these play a general role in parasitic lifestyle.

Analysis of the proteins expressed from key gene families indicates that parasite-specific genes are the most highly expressed during both the spore and vegetative or asexual states, indicating their importance in microsporidian biology. Also interesting is the fact that some new genes have been gained horizontally from bacteria.

Further research into the genes key for parasitic success may shed light on mechanisms of pathogenicity leading to possible therapeutic solutions. Published in many peer-reviewed journals including the prestigious Nature and Current Biology, EVOGCPROTO research results represent a major step forward in a socially and economically important area of biology.