Differential accumulation of mutations localized in particular domains of the mucin genes expressed in the vertebrate host stage of Trypanosoma cruzi.
The surface of Trypanosoma cruzi is covered by mucin-type glycoproteins involved in parasite protection, attachment and immunoevasion. The gene family coding for the mucins expressed by the parasite in the vertebrate host, named TcMUC, is composed of several hundred members and presents high variability. The genes encoding mucins expressed in the insect-dwelling parasite stages are part of a much more homogeneous family, named TcSMUG. Here, we addressed the organization and evolution of physically linked T. cruzi mucin genes by sequencing large chromosomal fragments containing these genes. Specific accumulation of mutations was restricted to particular domains of TcMUC genes, showing that these regions have, or have had, an accelerated evolution rate. Sequence analysis of several TcMUC genes allowed for the identification of members sharing features of TcMUC I and II, thus evidencing that one group of genes was generated from the other. The highly conserved intergenic regions of both TcMUC and TcSMUG families contained TG-rich microsatellites that were not present in unrelated genes in the cosmids, suggesting a role for homologous recombination in shuffling and/or amplification of T. cruzi mucin genes. The comparison of putative homologous TcMUC II genes from different strains of T. cruzi showed that their central variable domains are conserved. This conservation was always higher at the DNA level suggesting positive selection in these particular regions of TcMUC II genes.
Campo
Vanina
V
Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús Universidad Nacional de General San Martín and Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.
Di Noia
Javier M
JM
Buscaglia
Carlos A
CA
Agüero
Fernán
F
Sánchez
Daniel O
DO
Frasch
Alberto C C
AC
D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D016054:DNA, Protozoan / Q000737:chemistry; D017125:Genes, Protozoan; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D009077:Mucins / Q000235:genetics*; D005810:Multigene Family; D009154:Mutation; D010802:Phylogeny; D021382:Protein Sorting Signals; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D017385:Sequence Homology; D020080:Tandem Repeat Sequences; D014349:Trypanosoma cruzi / Q000145:classification / Q000235:genetics* / Q000254:growth & development*
D016054:DNA, Protozoan; D009077:Mucins; D021382:Protein Sorting Signals