Medicinal Leech Draft Genome — Anticoagulant Gene Survey

Draft genome of Hirudo medicinalis: 15 known anticoagulation factors and 17 other antihemostasis-linked proteins

Genomics & ProteomicsKvist S, Manzano-Marín A, de Carle D, Trontelj P, Siddall ME (2020)— Scientific ReportsDOI →

Why This Matters for Hirudotherapy

A genome-level reference for the medicinal leech that supports comparative studies of leech anticoagulants and the search for new candidate molecules.

Investigational / Research Priority

Basic science research. This review covers genomic findings with indirect translational implications for future drug discovery.

Last Updated: May 27, 2026Reviewed by: Andrei Dokukin, MD

Omics & molecular biologyDiscovery science

The need for a reference genome

Despite centuries of medical use, Two draft genomes of Hirudo medicinalis were published in 2020: Babenko et al. (BMC Genomics, 29 April) and Kvist et al. (Scientific Reports, 18 June). The Kvist draft is estimated to cover 79–94% of the genome, and searched it for anticoagulation factors.[R1]

Assembly statistics

176.96

Megabase pairs (Mbp)

19,929

Scaffolds

79–94%

Estimated share of the genome sequenced

Anticoagulant gene catalog

The study’s primary contribution was a thorough catalog of genes encoding anticoagulation and antihemostatic proteins. The researchers annotated:

15 anticoagulation factors

Leech-derived proteins with matches in the genome include hirudin (a single copy), eglin C and destabilase I (seven copies each, the highest copy numbers), bdellin, antistasin, bdellastasin, guamerin, piguamerin, LDTI, cystatin, manillase, C-type lectin, ficolin and Kazal-type serpins. C-type lectin, guamerin, Kazal-type serpin and bdellin occur in tandem arrays. A BLAST hit to lefaxin was not accepted as an orthologue.

17 antihemostatic proteins

Anticoagulation-related proteins known from other blood-feeding or venomous animals (for example ADAMTS, apyrase, Kunitz-type serine protease inhibitors, annexin and snake-venom proteins); 17 of 23 BLAST hits were supported as orthologous. The authors note that no match to the leech antiplatelet proteins (LAPP/saratin) was recovered, and the potency of the newly identified proteins remains to be investigated.

Novel discoveries

Selected findings from the Kvist draft genome (single-copy hirudin and hirudin-like factor 3; seven copies each of eglin C and destabilase) and from the Babenko et al. 2020 genome and salivary-cell data (CRISP proteins, M12/M13 proteases):

Discovery	Significance
CRISP proteins (Babenko et al. 2020)	Cysteine-rich secretory proteins (CAP/CRISP superfamily); the identified sequences resemble the hookworm potassium-channel blocker AcK1, the possible platelet aggregation inhibitor HPI and the snake toxins triflin and natrin-1; their function in the leech is not established
M12/M13 proteases	Metalloproteases of the M12, M13 and M28 families were the major enzymatic components of the salivary cell secretion (Babenko et al. 2020); M12 proteases can degrade extracellular-matrix proteins (gelatine, fibrinogen, fibronectin) and participate in clot softening by fibrinogen degradation

Drug discovery implications

The Kvist et al. draft genome provides a catalogue of candidate sequences for comparative studies of leech anticoagulants; the authors state that the potency of the newly identified proteins remains to be investigated. Babenko et al. describe their genome annotation as a database of sequences encoding unique bioactive leech proteins for use in developing novel pharmacological compounds.

Bivalirudin

Hirudin-inspired direct thrombin inhibitor. FDA-approved. Peak revenue $636M/year. Now generic.

Desirudin

Recombinant hirudin for DVT prophylaxis. FDA-approved in 2003 (Iprivask); now discontinued in the US. Demonstrates the path from leech compound to drug.

Lefaxin (preclinical)

A factor Xa inhibitor first isolated from the leech Haementeria depressa (Faria et al. 1999). In the H. medicinalis genome Kvist et al. found a BLAST hit to lefaxin, but did not accept it as an orthologue because the reciprocal BLAST gave a far better hit to hemerythrin.

Complementary proteomics

The Kvist draft genome is best read alongside Babenko et al. (2020), which reported an earlier, independently assembled H. medicinalis genome draft (BMC Genomics, 29 April 2020) and used mass spectrometry to identify 189 proteins in the salivary cell secretion of H. medicinalis (344 in H. verbana). Together they link genes to the proteins the leech actually secretes.

See genomics-proteomics for the broader omics summary.

References

[R1]
Draft genome of the European medicinal leech Hirudo medicinalis (Annelida, Clitellata, Hirudiniformes) with emphasis on anticoagulants
Scientific Reports(2020)https://doi.org/10.1038/s41598-020-66749-5
Primary source (Kvist et al., PMID 32555498).
[R2]
In-depth profiles of bioactive large molecules in saliva secretions of leeches determined by combining salivary gland proteome and transcriptome data
Journal of Proteomics(2019)https://doi.org/10.1016/j.jprot.2019.03.009
Liu et al. 2019 (PMID 30880165): 434 full-length salivary protein sequences deduced; the abstract does not name the species.
[R3]
Draft genome sequences of Hirudo medicinalis and salivary transcriptome of three closely related medicinal leeches
BMC Genomics(2020)https://doi.org/10.1186/s12864-020-6748-0
Babenko et al. 2020 (PMID 32349672): an independently assembled H. medicinalis genome draft (published 29 April 2020, before Kvist et al.) plus salivary transcriptomes and proteomics of three Hirudo species.

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