Evolution of Hematophagy in Ticks: Common Origins for Blood Coagulation and Platelet Aggregation Inhibitors from Soft Ticks of the Genus Ornithodoros

Abstract

Identification and characterization of antihemostatic components from hematophagous organisms are useful for the elucidation of the evolutionary mechanisms involved in adaptation to a highly complex host hemostatic system. Although many bioactive components involved in the regulation of the host's hemostatic system have been described, the evolutionary mechanisms of how arthropods adapted to a blood-feeding environment have not been elucidated. This study describes common origins of both blood coagulation inhibitors and platelet aggregation inhibitors (PAIs) from soft ticks of the genus Ornithodoros. Neighbor-joining analysis indicates that fXa, thrombin, and PAIs share a common ancestor. Maximum parsimony analysis and a phylogeny based on root mean square deviation values of alpha-carbon backbone structures suggest a novel evolutionary pathway by which different antihemostatic functions have evolved through a series of paralogous gene duplication events. In this scenario, the thrombin inhibitors preceded the fXa and PAIs. This evolutionary model explains why the tick serine protease inhibitors have inhibition mechanisms that differ from that of the canonical bovine pancreatic trypsin inhibitor (BPTI)-like inhibitors. Higher nonsynonymous-to-synonymous substitution rates indicate positive Darwinian selection for the fXa and PAIs. Comparison with hemostatic inhibitors of hard ticks suggests that the two main tick families have independently evolved novel antihemostatic mechanisms. Independent evolution of these mechanisms in ticks points to a rapid divergence between tick families that could be dated between 120 and 92 MYA. This coincides with current molecular phylogeny views on the early divergence of modern birds and placental mammals in the Late Cretaceous, which suggests that this event might have been a driving force in the evolution of hematophagy in ticks.

Association of bovine Toll-like receptor 4 with tick infestation rates and blood histamine concentration

“…Oliveira et al (2010) have summarized the six categories of active molecules from the salivary glands of ticks: 1) prostaglandin (Bowman et al, 1995); 2) histamine band proteins (Arocha-Pinango et al, 1999); 3) platelet aggregation inhibitor (Mans et al, 2002); 4) thrombin inhibitor (Liao et al, 2009); 5) antimicrobial protein (Lai et al, 2004b); and 6) an opioid peptide analog identified from neuroganglion, which is believed to inhibit algesthesia in the host (Lai et al, 2004a,b). The domain that mediates inflammation in the allergic reaction caused by these bioactive molecules is histamine.…”

Exploring the sialome of the blood-sucking bug Rhodnius prolixus

“…Although we know the function for some of these proteins, as indicated above, most of these novel proteins have unknown function. The probable scenario for the evolution of these lipocalins, as proposed for the evolution of BPTI salivary proteins in Ornithodorus ticks (Mans et al, 2002), must have been several events of gene duplication and divergence of function. While lipocalins have also been found in tick saliva performing similar functions as in Rhodnius, such as histamine and serotonin binding (Paesen et al, 2000;Sangamnatdej et al, 2002), this contrasts with mosquitoes and sand flies, where no salivary lipocalins have been described to date, although another family of small ligand-binding proteins, the OBP (Hekmat-Scafe et al, 2000), have evolved into the D7 subfamily found in blood-sucking Diptera (Valenzuela et al, 2002a).…”

Evolution of the tissue factor pathway inhibitor-like Kunitz domain-containing protein family in Rhipicephalus microplus

“…Such expansions are present in both hard and soft ticks but are lineagespecific as they occurred after the divergence of the major tick families. They therefore coincided with the independent adaptation of the hard and soft ticks to a blood-feeding environment (Mans et al, 2002b(Mans et al, , 2008aMans and Neitz, 2004). Such adaptations would have required the evolution of proteins with novel functions that could facilitate blood-feeding behaviour and this was likely the evolutionary stimulus that resulted in the expansion of so many secretory protein families.…”

“…These lineage-specific expansions likely occurred during individual adaptations of hard and soft ticks to blood-feeding behaviour after their divergence from the ancestral tick (Mans et al, 2002b(Mans et al, , 2008aMans and Neitz, 2004). It is apparent that the Kunitz protein families are of integral importance to the haematophagous lifestyle of both hard and soft ticks.…”

“…Previous studies have shown that this protein family has evolved through gene duplication within the main tick families but after the divergence of hard and soft ticks (Mans et al, 2002b(Mans et al, , 2008aMans and Neitz, 2004). The Kunitz protein family has therefore expanded in response to the blood-feeding environment that the Ixodidae and Argasidae encountered individually.…”