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Viral sequence integration into introns of chemokine receptor genes
Viral DNA sequences are able to integrate into the non-coding DNA sections of the genome of human cells which have been infected, either spontaneously or experimentally. We have made a data-base search for integration events of non-endogenous viruses into the introns of chemokine receptor sequences. A BLAST search of all viral DNA sequences, using the intronic sequences as "Query," returned several significant alignments. However, due to the high reiteration rate of the non-coding sequences in the human genome, it became necessary to re-examine the individual alignments to verify whether the virus-flanking intronic sequence was really located in a chemokine receptor intron. We found only one unquestionable event of viral insertion of a section of a long terminal repeat of the murine leukemia virus within the first intron of the CC chemokine receptor 7 gene. Possible biological effects of such an insertion are discussed. Further experimental or clinical research could demonstrate the occurrence of other intronic viral insertions in human chemokine receptor genes
Mutation, selection, and functional repair in formyl peptide receptor genes: a view on the selection processes occurring in this gene subfamily.
Evidence for endogenous retroviruses in human chemokine receptor gene introns: possible evolutionary inferences and biological roles
The human chemokine receptor (CKR) genes CCR2, CCR6, CCR7, CCR9, CCR10, CXCR4, and CXCR5 harbor one or two
introns. CCR7, CCR9, CCR10, and CXCR5 introns, (but not CCR2, CCR6, and CXCR4 introns) encompass retrovirus-like
inserts with the characteristics of SINEs (short interspersed nuclear elements) up to 300 nucleotides (nt) long. Other
characteristic elements of the retroviral genome, such as long terminal repeats and gag, pol, and env genes, are
lacking. The inserts likely derived from one (or more) of the following retroviruses: XA34 (NCBI GenBank Nucleotides,
U29659), HERV-P-T47D (AF087913), ERV FTD (U27241), HERV-K (Y17832), HML6p (U86698), HERV-H/env60 (AJ289710),
XA38 (U37066). Virus-like inserts are remarkably homogeneous in all CKR introns, with nt identities of about 80%.
Percentages of nt identities between the CKR inserts and the corresponding viral sequences are also about 80%. With
reference to the CKR sequence, the viral sequence aligns in some instances Plus/Plus (XA34, HML6p, HERV-H/env60,
and XA38) and in other instances Plus/Minus (HERV-P-T47D, ERV FTD, and HERV-K). Some aspects of the evolution of
retroviruses and CKRs as well as hypotheses on the biological significance of the SINE inserts are discussed
Differential Conservation of Nucleotides and Conservation/Mutation Correlations Between Nucleotides, with Special Reference to CXC 1 and 4 and FP Receptors Involved in Immune Regulation
Random mutations of the first nucleotide of a coding triplet alter the hydropathic character of 27 % of the hydrophobic amino acids and of 23 % of the hydrophilic amino acids, while random mutations of the second nucleotide alter the hydropathic character of 82 % of the hydrophobic amino acids and of 47 % of the hydrophilic amino acids. In cases of a change of the hydropathic character, a second random mutation in the previously unmutated first or second nucleotide causes reversion to the original character of an additional 11 % of the originally hydrophobic-coding triplets and an additional 14 % of the originally hydrophilic-coding triplets (on average). Thus, a selection oriented towards the preservation of the hydropathic character of amino acids may be expected to eventually result in a higher conservation of the second nucleotide (as compared to the first). In the case of uncorrected mutations of one of the two first nucleotides, it may be expected that appropriate second mutations in the other unaffected nucleotide will be positively selected. This would result in a positive correlation between the conservation/mutation indexes of the two first nucleotides, as these would be prevailingly either both conserved or both mutated. We examined six groups of coding mRNA sequences: chemokine CXC 1 and 4 and formyl peptide receptors; a group comprising different receptors of the rhodopsin-like superfamily, together with some viral sequences which share significant homologies with these receptors; a group of viral sequences with homologies with the rhodopsin-like receptors; a group of solute carriers. In all the experimental groups the second nucleotide of the triplet was the most conserved and a significant positive correlation existed between conservation/mutation indexes of the two first nucleotides. Similar conservation/mutation patterns could be of more general occurrence in the genome, as a consequence of selection processes
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