School of Mathematics

Alessandro Moura

Why are replication origins located where they are?

DNA replication in yeast and many other organisms starts from precise locations on the genome, called replication origins.  The way the origins are distributed in the chromosomes is particularly important in ensuring that replication is completed quickly, and that no regions of the genome take too long to be replicated.  This raises the possibility that the spatial distribution of origins is affected by selection pressures.  In this work we put forth the hypothesis that the minimisation of the replication time is one of the main determinants of the origin locations.  Using a simple mathematical model, we show that our hypothesis predicts that highly efficient origins tend to be isolated from other origins, whereas inefficient ones tend to be clustered together. We also predict that the distance between neighbouring origins is strongly correlated with the difference in their firing times.  We test these predictions using data recently obtained through next-generation sequencing methods, and show that they are supported by the data.