Adhesion molecules and other secreted host-interaction determinants in Apicomplexa: insights from comparative genomics.
Apicomplexa have developed distinctive adaptations for invading and surviving within animal cells. Here a synthetic overview of the diversity and evolutionary history of cell membrane-associated, -secreted, and -exported proteins related to apicomplexan parasitism is presented. A notable feature in this regard was the early acquisition of adhesion protein domains and glycosylation systems through lateral transfer from animals. These were utilized in multiple contexts, including invasion of host cells and parasite-specific developmental processes. Apicomplexans possess a specialized version of the ancestral alveolate extrusion machinery, the rhoptries and micronemes, which are deployed in invasion and delivery of proteins into host cells. Each apicomplexan lineage has evolved a unique spectrum of extruded proteins that modify host molecules in diverse ways. Hematozoans, in particular, appear to have evolved novel systems for export of proteins into the host organelles and cell membrane during intracellular development. These exported proteins are an important aspect of the pathogenesis of Plasmodium and Theileria, being involved in response to fever and in leukocyte proliferation respectively. The complement of apicomplexan surface proteins has primarily diversified via massive lineage-specific expansions of certain protein families, which are often coded by subtelomeric gene arrays. Many of these families have been found to be central to immune evasion. Domain shuffling and accretion have resulted in adhesins with new domain architectures. In terms of individual genes, constant selective pressures from the host immune response has resulted in extensive protein polymorphisms and gene losses. Apicomplexans have also evolved complex regulatory mechanisms controlling expression and maturation of surface proteins at the chromatin, transcriptional, posttranscriptional, and posttranslational levels. Evolutionary reconstruction suggests that the ancestral apicomplexan had thrombospondin and EGF domain adhesins, which were linked to the parasite cytoskeleton, and played a central role in invasion through formation of the moving junction. It also suggests that the ancestral parasite had O-linked glycosylation of surface proteins which was partially or entirely lost in hematozoan lineages.
Anantharaman
Vivek
V
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
Iyer
Lakshminarayan M
LM
Balaji
S
S
Aravind
L
L
D000818:Animals; D016782:Apicomplexa / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D005075:Biological Evolution; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D023281:Genomics; D006790:Host-Parasite Interactions; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D015800:Protozoan Proteins