THE TRYPANOSOMA-CRUZI MUCIN FAMILY IS TRANSCRIBED FROM HUNDREDS OF GENES HAVING HYPERVARIABLE REGIONS

In previous works we have identified genes in the protozoan parasite T rypanosoma cruzi whose structure resemble those of mammalian mucin gen es. Indirect evidence suggested that these genes might encode the core protein of parasite mucins, glycoproteins that were proposed to be in volved in the interaction with, and invasion of, mammalian host cells. We now show that the mucin gene family from T. cruzi is much larger a nd diverse than expected. A minimal number of 484 mucin genes per hapl oid genome is calculated for a parasite clone. Most, if not all, genes are transcribed, as deduced from cDNA analysis. Comparison of the cDN A sequences showed evidences of a high mutation rate in localized regi ons of the genes. Sequence conservation among members of the family is much higher in the untranslated (UTR) regions than in the sequences e ncoding the mature mucin core protein. Transcription units can be clas sified into two main subfamilies according to the sequence homologies in the 5'-UTR, whereas the 3'-UTR is highly conserved in all clones an alyzed. The common origin of members of this gene family as well as th eir relationships can be defined by sequence comparison of different d omains in the transcription units. The regions encoding the N and C te rmini, supposed to correspond to the leader peptide and membrane-ancho ring signal, respectively, (Di Noia, J. M., Sanchez, D. O., and Frasch , A. C. C. (1995) J. Biol. Chem. 270, 24146-24149) are highly conserve d. Conversely, the central regions are highly variable. These regions encode the target sites for O-glycosylation and are made of a variable number of repetitive units rich in Thr and Pro residues or are nonrep etitive but still rich in Thr/Ser and Pro residues. The region putativ ely coding for the N-terminal domain of the mature core protein is hyp ervariable, being different in most of the transcripts sequenced. Nonr epetitive central domains are unique to each gene. Gene-specific probe s show that the relative abundance of different mRNAs varies greatly w ithin the same parasite clone.