a1 Centre for Immunity, Infection and Evolution, and Institute for Immunology and Infection Research, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland
a2 Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, EH26 0PZ, Scotland
The transforming growth factor-β (TGF-β) gene family regulates critical processes in animal development, and plays a crucial role in regulating the mammalian immune response. We aimed to identify TGF-β homologues from 2 laboratory model nematodes (Heligmosomoides polygyrus and Nippostrongylus brasiliensis) and 2 major parasites of ruminant livestock (Haemonchus contortus and Teladorsagia circumcincta). Parasite cDNA was used as a template for gene-specific PCR and RACE. Homologues of the TGH-2 subfamily were isolated, and found to differ in length (301, 152, 349 and 305 amino acids respectively), with variably truncated N-terminal pre-proteins. All contained conserved C-terminal active domains (>85% identical over 115 amino acids) containing 9 cysteine residues, as in C. elegans DAF-7, Brugia malayi TGH-2 and mammalian TGF-β. Surprisingly, only the H. contortus homologue retained a conventional signal sequence, absent from shorter proteins of other species. RT-PCR assays of transcription showed that in H. contortus and N. brasiliensis expression was maximal in the infective larval stage, and very low in adult worms. In contrast, in H. polygyrus and T. circumcincta, tgh-2 transcription is higher in adults than infective larvae. The molecular evolution of this gene family in parasitic nematodes has diversified the pre-protein and life-cycle expression patterns of TGF-β homologues while conserving the structure of the active domain.
(Received February 25 2009)
(Revised April 15 2009)
(Accepted April 21 2009)
(Online publication August 28 2009)
c1 Corresponding author: Institute of Immunology and Infection Research, University of Edinburgh, Ashworth Laboratories, West Mains Road, Edinburgh EH9 3JT, Scotland. Fax: +44 131 650 5450. E-mail: firstname.lastname@example.org
p1 Current address: Queensland Institute for Medical Research, Brisbane, Australia.