Formyl Peptide Receptors on Immune and Nonimmune Cells: Analysis of Sequence Conservation in FPR Genes

• Published in: Immunopharmacology and immunotoxicology Vol. 29; no. 2; pp. 243 - 269
• Main Authors: Panaro, M.A., Acquafredda, A., Sisto, M., Lisi, S., Calvello, R., Mitolo, C.I., Cianciulli, A., Mitolo, V.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01-01-2007; Taylor & Francis
• Subjects: Amino Acid Sequence; Animals; Bacteria; Conserved Sequence; Data Interpretation, Statistical; Dogs; Formyl peptide receptors; FPR1; Humans; Immunity; Immunity, Cellular - physiology; Macaca mulatta; Mice; Molecular Sequence Data; Mutation - genetics; Mutation - physiology; Nucleotides - chemistry; Rabbits; Rats; Receptors, Formyl Peptide - physiology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Vertebrates
• ISSN: 0892-3973; 1532-2513
• DOI: 10.1080/08923970701512544

Formyl peptides are oligopeptides released by Gram-negative bacteria. So far, specific formyl peptide receptors (FPRs) have been described in mammals only. FPRs are seven-transmembrane G-coupled molecules and make up a relatively homogeneous group, although exhibiting different levels of affinity for the ligands. We examined the patterns of conservation mutation within the FPR group of genes, as studied in 16 mRNAs from different species. Following alignment of the coding sections, those nucleotides identical in at least 15 sequences were assigned a "conservation index" 2; those with 8-14 identities an index 1; those with less than 8 identities an index zero. The cumulative average conservation index was 1.36. The autocorrelation function and the power spectrum of the whole series of indexes demonstrated a 3-unit periodicity. This periodicity is explained by the fact that the average conservation indexes of the first, second and third nucleotides of the coding triplets were 1.46, 1.55 (both above the mean), and 1.06 (below the mean), respectively, so that correlations at lag 3 tend to be all positive. In mRNAs, regardless of the position in the coding triplets, T is significantly more frequently conserved (average index = 1.60) than A, C, and G (1.21 - 1.38). In the nucleotides with conservation index 1 or zero, we recorded the two more frequently represented bases. In 35% of mRNA nucleotides the two more frequently represented bases were C and T; in 28% of cases the two more frequently represented bases were A and G; other couples occurred with lower frequencies. Both mutations may arise following C methylation with subsequent transformation into T (by deamination), either in the template or the coding DNA strand. Thus, we hypothesized that in FPR mRNAs there is an evolutionary trend of transformation from G to A and from C to T, the latter being the more stable of the bases.