Length of the hypermutation motif DGYW/WRCH in the focus of statistical limits. Implications for a double-motif or extended motif recognition models.
The motif DGYW/WRCH (Mh) and its frequently discussed simplified derivative GYW/WRC (Mhs) are involved in immunoglobulin (Ig) hypermutation. Both these motifs appear to be markedly shorter than the corresponding conventionally predicted minima of valid sequence lengths (MVSL). The same conclusion concerning both Mh and Mhs can also be obtained in the combined case including a less strict semi-empirically defined w-value and one nucleotide length tolerance related to MVSL. Such disagreement indicates considerably low information content in Mh and Mhs when evaluating these motifs as alphabetical structures (words). This fact raises a question of actually recognized structures (presumably longer than Mh and Mhs). Interestingly, both Mh and Mhs dimers or pairs of closely located Mh or Mhs achieve confirmation of length validity in the case of w=0.05, suggesting thus double-motif recognition as one of statistically consistent explanations. This possibility is also in agreement with the results of our model sequence study of mRNA derived from variable Ig gene sequences (rIgV) with respect to the most frequently occurring structures formed by motif overlaps in all model sequence sets. On the other hand, additional superior occurrence of motif pairs at a structurally important distance of a single DNA thread was found in the conserved domain (cd00099) related sequences of Elasmobranchii origin and less markedly in the corresponding human rIgV, but not in a randomly selected human subset of rIgV. The data are discussed with respect to statistical evaluation and structural properties of hypermutation motifs or the competent enzyme, i.e. activation-induced cytidine deaminase.
Kubrycht
Jaroslav
J
Laboratory of Biotransformation, National Institute of Public Health, 10042 Prague 10, Czech Republic. jkub@post.cz
Sigler
Karel
K
D020816:Amino Acid Motifs; D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics; D004252:DNA Mutational Analysis; D004789:Enzyme Activation; D005803:Genes, Immunoglobulin; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D017434:Protein Structure, Tertiary; D027041:Somatic Hypermutation, Immunoglobulin
D003564:Cytidine Deaminase