On the Border of Order: Chromosomal Organization in Space and Time*

Many processes in biology, from antibody production to tissue differentiation, share a common fundamental step — establishing physical contact between distant genomic segments. A key outstanding question is then: How do genomic segments that are strung out over millions of base pairs along the DNA find each other in the crowded cell on a remarkably short timescale? This question, fundamental to biology, can be recognized as the physics problem of the first-passage time. We show how concepts from statistical physics help reveal the physical principles by which cells solve this first-passage problem with astonishing efficiency. We illustrate these ideas in the context of adaptive immunity – the system that enables the individual to respond to a great variety of pathogens through a diverse repertoire of antibodies.