Investigating hypothetical products from noncoding frames (HyPNoFs)

Abstract

Hypothetical Products from Noncoding Frames (i.e., HyPNoFs) are hypothetical, not-coded proteins, translated from alternate reading frames (i.e., coding + 1 and coding + 2) of cDNAs. HyPNoFs of CD4, PKC, oncostatin, bcl-2 proto-oncogene, tumor suppressor p53, cystic fibrosis transmembrane regulator (CFTR), and tumor necrosis factors alpha and beta were searched as query sequences vs the SWISS-PROT data bank. Homology searchers carried out revealed that hypothetical products (i.e., HyPNoFs) may share high similarity with real protein products actually coded. Sequence similarity of hypothetical products to real proteins is sometimes very high, suggesting common conformational features, according to the Sander and Schneider cutoff value. This finding supports the hypothesis that eukaryotic DNA, currently considered to be monocistronic, might occasionally have polycistronic regions, carrying different protein messages on overlapping frames. As yet, polycistronic genes have been observed in viral genomes only. The presence of polycistronic regions in eukaryotic genes is likely reminiscent of an ancient strategy, rather than a present feature of the genome in eukaryotes. These data suggest that thorough investigation of HyPNoFs is likely to improve our ability to trace genes' evolution and to investigate structure-function relationships of protein and DNA sequences.

A COMPUTATIONAL STRATEGY TO INVESTIGATE RELEVANT SIMILARITIES BETWEEN VIRUS AND HUMAN PROTEINS - Local High Similarities between Herpes and Human Proteins

“…Consistent with these findings, a strong rational supports the investigation of human-to-viral structural-functional relationships based, at least in some cases, onto a common-antigen sharing process. We have previously suggested unexpected evolutionary relations between human-lymphocytes CD4 receptor and his counterpart HIV-capsid-constituent GP120 (Facchiano, 1995;Facchiano, 1996); allele variability has been related to viral infection and susceptibility, with a significant association of HIV progression with patients HLA status (Limou, 2009;Fellay, 2007). Based on significant proteins similarities we have also suggested the occurrence of molecular mimicry between pathogens and human proteins possibly underlying different diseases (Benvenga, 1995;Benvenga, 1999;Benvenga, 2003).…”