Abstract

The class A scavenger receptor (cA-SR) family is a group of five evolutionarily related innate immune receptors. The cA-SRs are known for their promiscuous ligand binding; as they have been shown to bind bacteria, such as Streptococcus pneumoniae and Escherichia coli, as well as different modified forms of low-density lipoprotein. Three of the five family members possess a scavenger receptor cysteine-rich (SRCR) domain while the remaining two receptors lack the domain. Previous work has suggested that the macrophage-associated receptor with collagenous structure (MARCO) shares a recent common ancestor with the non-SRCR-containing receptors; however, the origin of the SRCR domain within the cA-SRs remains unknown. We hypothesize that the SRCR domains of the cA-SRs have a common origin that predates teleost fish. Using the newly available sequence data from sea lamprey and ghost shark genome projects, we have shown that MARCO shares a common ancestor with the SRCR-containing proteins. In addition, we explored the evolutionary relationships within the SRCR domain by reconstructing the ancestral SRCR domains of the cA-SRs. We identified a motif that is highly conserved between the cA-SR SRCR domains and the ancestral SRCR domain that consist of WGTVCDD. We also show that the GRAEVYY motif, a functionally important motif within MARCO, is poorly conserved in the other cA-SRs and in the reconstructed ancestral domain. Further, we identified three sites within MARCO’s SRCR domain, which are under positive selection. Two of these sites lie adjacent to the conserved WGTVCDD motif, and may indicate a potential biological function for these sites. Together, these findings indicate a common origin of the SRCR domain within the cA-SRs; however, different selective pressures between the proteins may have caused MARCOs SRCR domain to evolve to contain different functional motifs when compared to the other SRCR-containing cA-SRs.

Highlights

  • The scavenger receptors (SRs) are a group of pattern recognition receptors (PRRs), which were originally defined for their ability to bind forms of low-density lipoprotein (LDL) and are subdivided into 8 classes (A–H) [1, 2]

  • We hypothesize that SCAvenger Receptor class A member 3 (SCARA3) and SCAvenger Receptor class A member 4 (SCARA4) were generated through one duplication event, while macrophage-associated receptor with collagenous structure (MARCO) may have been generated from a duplication event of a SCAvenger Receptor class A member 5 (SCARA5)/scavenger receptor class A (SR-A) precursor

  • We are able to expand upon this previous work due to recent genome sequencing projects including the sea lamprey and ghost shark. This allowed for our analysis to include in total, 40 MARCO, 25 SR-A, 40 SCARA5, 40 SCARA4, and 40 SCARA3 protein sequences for this analysis

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Summary

Introduction

The scavenger receptors (SRs) are a group of pattern recognition receptors (PRRs), which were originally defined for their ability to bind forms of low-density lipoprotein (LDL) and are subdivided into 8 classes (A–H) [1, 2]. These receptors are extracellular glycoproteins, which mediate phagocytosis of negatively charged ligands [3]. This binding ability was later refined to include host-modified.

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