Homology, paralogy and function of DGF-1, a highly dispersed Trypanosoma cruzi specific gene family and its implications for information entropy of its encoded proteins

Homology, paralogy and function of DGF-1, a highly dispersed Trypanosoma cruzi specific gene family and its implications for information entropy of its encoded proteins

Author Kawashita, Silvia Y. Autor UNIFESP Google Scholar
Silva, Claudio V. da Autor UNIFESP Google Scholar
Mortara, Renato A. Autor UNIFESP Google Scholar
Burleigh, Barbara A. Google Scholar
Briones, Marcelo R. S. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Harvard Univ
Universidade Federal de Uberlândia (UFU)
Abstract Surface adhesion proteins are essential for Trypanosoma cruzi invasion of mammalian cells. Here we show that Dispersed Gene Family-1 (DGF-1) members, previously identified as nuclear repeated sequences present in several chromosomes and comprising the third largest T cruzi specific gene family, have conserved adhesin motifs including four segments with significant similarity to human beta 7 integrin. How cytometry and biotinylation assays with anti-DGF-1 antibodies indicated that, as expected, DGF-1 members are expressed on the trypomastigote surface. the DGF-1 genealogy, inferred using T cruzi Genome Project data and network phylogeny algorithms, suggests that this gene family is separated in at least three groups with differential distribution of functional domains. To identify which members of this gene family are expressed we used a combined approach of RT-PCR and codon usage profiles, showing that expressed members have a very biased codon usage favoring CC, whereas non-expressed members have a homogeneous distribution. Shannon information entropy was used to measure sequence variability and revealed four major high entropy segments in the extracellular domain of DGF-1 overlapping with important putative functional modules of the predicted proteins. Testing for natural selection, however, indicated that these high entropy segments were not under positive selection, which contradicts the notion that positive selection is the cause of high variability in specific domains of a protein relative to other less variable regions in the same molecule. We conjectured that members of the DGF-1 family might be associated with the ability of T cruzi to bind extracellular matrix proteins, such as fibronectin and laminin, and speculated on mechanisms that would be generating the localized diversity in these molecules in the absence of selection. (C) 2009 Elsevier B.V. All rights reserved.
Keywords Trypanosoma cruzi
Dispersed gene family-1
Shannon entropy
Codon usage
Integrin-like genes
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Howard Hughes Medical Institute (USA)
Grant number WHO: A10801
Date 2009-05-01
Published in Molecular and Biochemical Parasitology. Amsterdam: Elsevier B.V., v. 165, n. 1, p. 19-31, 2009.
ISSN 0166-6851 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 19-31
Origin http://dx.doi.org/10.1016/j.molbiopara.2008.12.010
Access rights Closed access
Type Article
Web of Science ID WOS:000264514600003
URI http://repositorio.unifesp.br/handle/11600/31500

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