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. 2023 Nov 12;14(11):2068.
doi: 10.3390/genes14112068.

Revisiting the Asian Buffalo Leech (Hirudinaria manillensis) Genome: Focus on Antithrombotic Genes and Their Corresponding Proteins

Zichao Liu  1 , Fang Zhao  2 , Zuhao Huang  2 , Qingmei Hu  1 , Renyuan Meng  1 , Yiquan Lin  2 , Jianxia Qi  3 , Gonghua Lin  2
Affiliations

Revisiting the Asian Buffalo Leech (Hirudinaria manillensis) Genome: Focus on Antithrombotic Genes and Their Corresponding Proteins

Zichao Liu et al. Genes (Basel). .

Abstract

Leeches are well-known annelids due to their obligate blood-feeding habits. Some leech species secrete various biologically active substances which have important medical and pharmaceutical value in antithrombotic treatments. In this study, we provided a high-quality genome of the Asian buffalo leech (Hirudinaria manillensis), based on which we performed a systematic identification of potential antithrombotic genes and their corresponding proteins. Combining automatic and manual prediction, we identified 21 antithrombotic gene families including fourteen coagulation inhibitors, three platelet aggregation inhibitors, three fibrinolysis enhancers, and one tissue penetration enhancer. A total of 72 antithrombotic genes, including two pseudogenes, were identified, including most of their corresponding proteins forming three or more disulfide bonds. Three protein families (LDTI, antistasin, and granulin) had internal tandem repeats containing 6, 10, and 12 conserved cysteines, respectively. We also measured the anticoagulant activities of the five identified hirudins (hirudin_Hman1 ~ hirudin_Hman5). The results showed that three (hirudin_Hman1, hirudin_Hman2, and hirudin_Hman5), but not the remaining two, exhibited anticoagulant activities. Our study provides the most comprehensive collection of antithrombotic biomacromolecules from a leech to date. These results will greatly facilitate the research and application of leech derivatives for medical and pharmaceutical purposes in the treatment of thrombotic diseases.

Keywords: anticoagulant activity; antithrombotic protein; gene family; genome; hirudin; leech.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scaffold and chromosome lengths of Hirudinaria manillensis genome.
Figure 2
Figure 2
Alignment of the archetypal hirudin (from H. medicinalis) and the hirudins identified from the H. manillensis genome. Red frame, signal peptide; red triangle, conserved cysteine; *, stop codon (similarly hereinafter).
Figure 3
Figure 3
(A) Alignment of the archetypal granulin (from H. nipponia) and progranulin identified from the H. manillensis genome; (B) Alignment of the five internal tandem repeats of the H. manillensis progranulin.
Figure 4
Figure 4
(A) Alignment of the archetypal antistasin (from Haemadipsa officinalis) and the antistasins identified from the H. manillensis genome; (B) Alignment of the five internal tandem repeats of the H. manillensis antistasin.
Figure 5
Figure 5
Alignment of the archetypal lefaxin (from H. depressa) and the lefaxins identified from the H. manillensis genome.
Figure 6
Figure 6
Alignment of the archetypal therostasin (from T. tessulatum) and the therostasin identified from H. manillensis.
Figure 7
Figure 7
Alignment and phylogenetic relationships of the archetypal hirustasin (from H. medicinalis), guamerin (from H. nipponia), piguamerin (from H. nipponia), bdellastasin (from H. medicinalis), and poecistasin (from H. manillensis) and their homologous proteins identified from the H. manillensis genome in this study.
Figure 8
Figure 8
Alignment of the archetypal eglin (from H. medicinalis) and the eglin identified from the H. manillensis genome.
Figure 9
Figure 9
Alignment of the archetypal bdellin (from H. medicinalis) and the bdellin identified from the H. manillensis genome.
Figure 10
Figure 10
(A) Alignment of the archetypal LDTI (from H. medicinalis) and the LDTI identified from the H. manillensis genome; (B) Alignment of the archetypal LDTI and two internal tandem repeats of the H. manillensis LDTI.
Figure 11
Figure 11
Alignment (A) and phylogenetic relationships (B) of the archetypal HMEI-A and HMEI-B (from H. manillensis) and the HMEIs identified from the H. manillensis genome in this study.
Figure 12
Figure 12
Alignment of the archetypal saratin (from H. officinalis) and the saratins identified from the H. manillensis genome.
Figure 13
Figure 13
Alignment of the archetypal apyrase (from H. robusta) and the apyrases identified from the H. manillensis genome.
Figure 14
Figure 14
Alignment of the archetypal lumbrokinase (from L. rubellus) and the lumbrokinases identified from the H. manillensis genome.
Figure 15
Figure 15
Alignment of the archetypal destabilase (from H. medicinalis) and the destabilases identified from the H. manillensis genome.
Figure 16
Figure 16
Alignment of the archetypal GGT (from H. medicinalis) and the GGT identified from the H. manillensis genome.
Figure 17
Figure 17
Alignment of the archetypal LCI (from H. medicinalis) and the LCI identified from the H. manillensis genome.
Figure 18
Figure 18
Alignment of the archetypal hyaluronidase (from H. nipponia) and the hyaluronidases identified from the H. manillensis genome.
Figure 19
Figure 19
Phylogenetic relationship of the five hirudins hirudin_Hman1 ~ hirudin_Hman5 identified from this study and all available protein sequences whose anticoagulant activity had been measured (red, active proteins; blue, inactive proteins; A, clade in which all hirudins are active proteins; B, clade containing both active and inactive hirudins; B1, subclade in which all hirudins are active proteins; B2, subclade in which all hirudins are inactive proteins).
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