cruzi and L. major (15). The majority of species-specific genes – of which T. cruzi (32%) and T. brucei (26%) have a much greater proportion than L. major (12%) – occur at non-syntenic chromosome-internal

and subtelomeric regions and consist of members of large surface antigen families. These gene family expansions, along with structural RNAs and retroelements, are often associated with breaks in synteny. Gene divergence, acquisition and loss, and rearrangements within and between syntenic regions have shaped the genomes of the trypanosomatids (15). A remarkable Fulvestrant cell line feature of the T. brucei and T. cruzi genomes is the extensive expansion of species-specific genes, the large majority encoding surface proteins, such as Variant Surface Glycoproteins (VSGs) in T. brucei, trans-sialidase superfamily, mucin-associated surface proteins and mucins (TcMUC) among others in T. cruzi, all of them likely involved in important host-parasite interactions (15). These surface protein-encoding genes are often clustered into large arrays that can be as large as 600 kb and are/were subjected to intense rearrangements during the parasites’ evolution (15,20). It is likely therefore

that much of the striking polymorphism among the T. cruzi and T. brucei isolates that are reflected in several epidemiological and pathological aspects of Chagas disease and African sleeping sickness may be in part because of variability within these regions. Whole genome comparisons Compound Library of distinct trypanosomatid lineages through would allow further investigation of this. A wide range of pathologies is found within trypanosomatid parasite lineages. Thus, there remains a considerable evolutionary and pathological

space yet to be explored through additional comparative sequencing (we define pathogenomics as the genome analysis of pathogens). With the advent of massively parallel sequencing technologies, sequencing of additional trypanosomatid strains can now be performed at a fraction of the cost of the sequencing of the reference genomes. The Wellcome Trust Sanger Institute (WTSI) has initiated such efforts. The recent sequencing of the genomes of several Leishmania species, causative agents of cutaneous, mucocutaneous and visceral leishmaniasis, is beginning to unravel many features of potential relevance to parasite virulence and pathogenesis in the host. When compared to L. major, the genomes of Leishmania braziliensis and L. infantum displayed a highly conserved gene content and order. However, two hundred genes with a differential distribution between the three species were identified (21,22). Perhaps most unexpected was the discovery that L. braziliensis genome retained the components (Argonaute and Dicer) of a putative RNA interference pathway, which are absent in L. major and L. infantum. A subsequent functional study demonstrated the presence of a strong RNAi activity in L. braziliensis (23).