Anomalous Diffusion of DNA Elements and First-Passage Times of Genomic Interactions

Yaojun Zhang
Department of Physics
UC San Diego


ABSTRACT

The most remarkable feature of human adaptive immune system is its ability to recognize and respond to millions of different antigens. The diverse repertoire of antigen-specific receptors is generated by a special form of genetic recombination, known as V(D)J recombination. To determine the mechanism by which chromosomal DNA segments move inside the cell nucleus, we analyzed the 3D trajectories of the V and DJ elements in B lymphocytes. We found that these DNA elements displayed fractional Langevin motion indicative of the viscoelastic hindrance from the surrounding network of proteins and chromatin fibers, including the neighboring segments of the chromatin fiber. Using fractional Langevin dynamics simulations and first-passage times analysis, we found that DJ elements reach a V element within minutes. We propose that the viscoelastic nature of the nuclear environment causes coding and regulatory DNA elements to bounce back and forth until specific genomic interactions are established.