Haem-responsive gene transporter enables mobilization of host haem in ticks

Open Biol. 2021 Sep;11(9):210048. doi: 10.1098/rsob.210048. Epub 2021 Sep 1.


Ticks, notorious blood-feeders and disease-vectors, have lost a part of their genetic complement encoding haem biosynthetic enzymes and are, therefore, dependent on the acquisition and distribution of host haem. Solute carrier protein SLC48A1, aka haem-responsive gene 1 protein (HRG1), has been implicated in haem transport, regulating the availability of intracellular haem. HRG1 transporter has been identified in both free-living and parasitic organisms ranging from unicellular kinetoplastids, nematodes, up to vertebrates. However, an HRG1 homologue in the arthropod lineage has not yet been identified. We have identified a single HRG1 homologue in the midgut transcriptome of the tick Ixodes ricinus, denoted as IrHRG, and have elucidated its role as a haem transporter. Data from haem biosynthesis-deficient yeast growth assays, systemic RNA interference and the evaluation of gallium protoporphyrin IX-mediated toxicity through tick membrane feeding clearly show that IrHRG is the bona fide tetrapyrrole transporter. We argue that during evolution, ticks profited from retaining a functional hrg1 gene in the genome because its protein product facilitates host haem escort from intracellularly digested haemoglobin, rendering haem bioavailable for a haem-dependent network of enzymes.

Keywords: HRG; auxotrophy; haem; ticks; transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arthropod Proteins / genetics
  • Arthropod Proteins / metabolism*
  • Digestive System / metabolism
  • Digestive System / parasitology*
  • Heme / metabolism*
  • Hemeproteins / genetics
  • Hemeproteins / metabolism*
  • Hemoglobins / metabolism*
  • Ixodes / metabolism*
  • Phylogeny
  • Sequence Homology
  • Tick Infestations / parasitology*
  • Transcriptome


  • Arthropod Proteins
  • Hemeproteins
  • Hemoglobins
  • Heme