A Cell-surface Phylome for African Trypanosomes

Abstract

The cell surface of Trypanosoma brucei, like many protistan blood parasites, is crucial for mediating host-parasite interactions and is instrumental to the initiation, maintenance and severity of infection. Previous comparisons with the related trypanosomatid parasites T. cruzi and Leishmania major suggest that the cell-surface proteome of T. brucei is largely taxon-specific. Here we compare genes predicted to encode cell surface proteins of T. brucei with those from two related African trypanosomes, T. congolense and T. vivax. We created a cell surface phylome (CSP) by estimating phylogenies for 79 gene families with putative surface functions to understand the more recent evolution of African trypanosome surface architecture. Our findings demonstrate that the transferrin receptor genes essential for bloodstream survival in T. brucei are conserved in T. congolense but absent from T. vivax and include an expanded gene family of insect stage-specific surface glycoproteins that includes many currently uncharacterized genes. We also identify species-specific features and innovations and confirm that these include most expression site-associated genes (ESAGs) in T. brucei, which are absent from T. congolense and T. vivax. The CSP presents the first global picture of the origins and dynamics of cell surface architecture in African trypanosomes, representing the principal differences in genomic repertoire between African trypanosome species and provides a basis from which to explore the developmental and pathological differences in surface architectures. All data can be accessed at: http://www.genedb.org/Page/trypanosoma_surface_phylome.

Cell Surface Proteomics Provides Insight into Stage-Specific Remodeling of the Host-Parasite Interface in Trypanosoma brucei*

“…We noticed that paralogs from large protein families (46) were well-represented among stage-specific surface proteins (Fig. 6, supplemental Fig.…”

“…The list of proteins comprising the T. brucei cell surface phylome (46) was kindly provided by Dr. Andrew Jackson. Families represented in the cell surface proteomes were analyzed with respect to stage-specificity of individual members.…”

“…Our discovery in the present work that stage-specific expression of distinct paralogs is common across multiple families argues against simple redundancy as the explanation for gene expansion. Moreover, some families are described to have undergone faster diversification since the divergence of African trypanosomes from other trypanosomatids (46), indicating that gene expansion confers a selective advantage. Thus, rather than redundancy, our results suggest surface protein families have expanded in response to the need for alternately expressed isoforms that are each tuned to a specific host environment, as has been suggested for the nucleoside transporter family (53).…”

DNA Recombination Strategies During Antigenic Variation in the African Trypanosome

“…However, recent trypanosome genome sequencing studies suggest that ESAG-rich BES may be a T. brucei-specific feature. In T. vivax and T. congolense, which also use antigenic variation for survival, homologues of most T. brucei ESAGs can be found, but they are not detectably linked to VSG in BES and may even provide distinct functions ASMscience.org/MicrobiolSpectrum (75). Examining how T. vivax and T. congolense prosper in their mammal hosts will reveal much about the relationship between VSG and ESAG co-expression and the role of transcriptional switching in antigenic variation.…”

“…Genomic analyses have challenged this assumption, revealing significant differences between the VSG archives in the three species (75,84). Whole genome comparisons revealed that in T. congolense there is no equivalent of the T. brucei a-VSG subfamily; in contrast, there are two b-VSG subfamilies and a much greater range of distinct C-terminal domains (15-20 CTD types, each of which are found to be associated with particular VSG subtypes, in contrast to the single CTD found in T. brucei).…”