Ng TCR organization and its influence on gene segment recombination probability.

Ng TCR organization and its influence on gene Y-27632 biological activity segment recombination probability. TCR V segments are separated by long intervals, J segments by shorter intervals (dashed lines); the ratio of log segment length to log spacing is approximately 1.4 for V segments and approximately 1.3 for J segments. Relative interval between successive V segments and the J segments in the TRA locus (top blue curve) declines logarithmically with a slope of approximately 1.3. Sine and cosine function value of the start nucleotides of each V segment extrapolated to the sense (green) and antisense (blue) DNA strands, demonstrate that the gene segments are accurately aligned once the logarithmic organization is accounted for. Hypothetically, the segment location on the two DNA helices being in-phase or Lonafarnib chemical information out-of-phase may impact the energetics of DNA ?RAG enzyme interaction and thus the probability amplitude (orange line, going from 0 to 1) for gene segment recombination analogous to wave interference phenomenon. In the model depicted, V1 location on the two helices is out of phase, V2 is partially in phase and V3 is completely in phase. Closely clustered together J segments are more likely to be in phase.from the rearranging segment, Db or Ja), may influence its usage in repertoire generation resulting in the periodic distribution of the V and J segment usage in T-cell clones when the locus is interrogated from the 50 to 30 end. Essentially, this means that using analytical techniques such as Fourier’s series, probability amplitudes may be determined for the various gene segments on the TCR loci based on their positions. It may be very likely that the recombination is most frequent for gene segments that occur at a certain `harmonic’ frequency. As an example in the data presented, the TRB-V segment clonal frequency appears to oscillate with a wavelength of approximately 50?0 000 radians from the TRB-D segment (figure 4). This organizational pattern is also observed in the distribution of V gene segments capable of recombining with TRD-D segments, which are approximately 100 000 radians apart on the TRA locus, scattered among the TRA-specific V genes (figure 3). It may be speculated that the gene segment distribution periods represent optimal energy distribution for recombination to occur on the long helical DNA molecule, analogous to the interference phenomenon encountered in wave mechanics. This is plausible because the DNA double helices may represent two superposed waves, and the gene segment location may lend itself to either constructive or destructive interference, impacting the interaction with RAG enzymes and recombination potential. This would in turn determine the probability amplitude of that gene segment being represented in the final T-cell clonal repertoire (figure 5). Evidence to support a role for varying energy distribution along the DNA molecules is beginning to emerge as, such as, in modelling electron clouds of DNA molecules as chains of coupled harmonic oscillators have demonstrated the association between the quantum entanglement in the electron clouds of DNA molecules and the local binding energy [39]. It has also been demonstrated that the lower energy requirements for bending and rotation of the CG-rich DNA sequences, allows more efficient bending of DNA molecules around histones, resulting in greater CG content around nucleosomal DNA [40]. In this theoretical paper, we demonstrate that the TCR loci have an iterative, logarithmically scal.Ng TCR organization and its influence on gene segment recombination probability. TCR V segments are separated by long intervals, J segments by shorter intervals (dashed lines); the ratio of log segment length to log spacing is approximately 1.4 for V segments and approximately 1.3 for J segments. Relative interval between successive V segments and the J segments in the TRA locus (top blue curve) declines logarithmically with a slope of approximately 1.3. Sine and cosine function value of the start nucleotides of each V segment extrapolated to the sense (green) and antisense (blue) DNA strands, demonstrate that the gene segments are accurately aligned once the logarithmic organization is accounted for. Hypothetically, the segment location on the two DNA helices being in-phase or out-of-phase may impact the energetics of DNA ?RAG enzyme interaction and thus the probability amplitude (orange line, going from 0 to 1) for gene segment recombination analogous to wave interference phenomenon. In the model depicted, V1 location on the two helices is out of phase, V2 is partially in phase and V3 is completely in phase. Closely clustered together J segments are more likely to be in phase.from the rearranging segment, Db or Ja), may influence its usage in repertoire generation resulting in the periodic distribution of the V and J segment usage in T-cell clones when the locus is interrogated from the 50 to 30 end. Essentially, this means that using analytical techniques such as Fourier’s series, probability amplitudes may be determined for the various gene segments on the TCR loci based on their positions. It may be very likely that the recombination is most frequent for gene segments that occur at a certain `harmonic’ frequency. As an example in the data presented, the TRB-V segment clonal frequency appears to oscillate with a wavelength of approximately 50?0 000 radians from the TRB-D segment (figure 4). This organizational pattern is also observed in the distribution of V gene segments capable of recombining with TRD-D segments, which are approximately 100 000 radians apart on the TRA locus, scattered among the TRA-specific V genes (figure 3). It may be speculated that the gene segment distribution periods represent optimal energy distribution for recombination to occur on the long helical DNA molecule, analogous to the interference phenomenon encountered in wave mechanics. This is plausible because the DNA double helices may represent two superposed waves, and the gene segment location may lend itself to either constructive or destructive interference, impacting the interaction with RAG enzymes and recombination potential. This would in turn determine the probability amplitude of that gene segment being represented in the final T-cell clonal repertoire (figure 5). Evidence to support a role for varying energy distribution along the DNA molecules is beginning to emerge as, such as, in modelling electron clouds of DNA molecules as chains of coupled harmonic oscillators have demonstrated the association between the quantum entanglement in the electron clouds of DNA molecules and the local binding energy [39]. It has also been demonstrated that the lower energy requirements for bending and rotation of the CG-rich DNA sequences, allows more efficient bending of DNA molecules around histones, resulting in greater CG content around nucleosomal DNA [40]. In this theoretical paper, we demonstrate that the TCR loci have an iterative, logarithmically scal.

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