UCSF

Homologous chromosome pairing is an important first step in Meiosis. It physically aligns the homologs at a close distance along their length so that they can exchange genetic information. This exchange of information increases genetic diversity and forms the basis for Mendelian inheritance. Homologous chromosome pairing also disentangles the chromosomeswhich prepares them for chromosome segregation later in the cell cycle. Errors in chromosome segregation lead to infertility, meiotic arrest, and chromosome number disorders. It is thus important to understand how this crucial first step in Meiosis is achieved. While a lot is known about the genetics of homologous chromosome pairing, much less is known about the physics of chromosome pairing. Even in an organism with relatively short chromosomes such as S. cerivisea, pairing is still a limiting step in Meiosis, taking hours to complete. At these timescales, photobleaching and phototoxicity are problematic, even when using very low intensity light. For these reasons, it has proved difficult to study this process live. The difficulty of studying this process experimentally motivated us to build a physical model. Our physical model simulates not only meiotic chromosomes, but the physical environment, constraints, and active motion that the chromosomes experience during pairing. We used this model to investigate how different features of Meiosis affect the rate of pairing and the resolution of interlocks. By modeling three strains of S. cerivisea in silico, and comparing our results to experimental data, we were also able to make a prediction about the distribution of binding sites along the length of the chromosomes. Finally, our model gives us detailed movies of interlock resolution events which are then used to build a step-by-step recipe for interlock resolution. Together, these results bring new insights to the physical process of homologous chromosome pairing.