Density gradient ultracentrifugation and whole genome sequences: Fine-tuning the correspondence

Since its introduction in the 1950's, analytical ultracentrifugation (AUC) of DNA in CsCl and other salt density gradients at sedimentation equilibrium has remained an elegant way to gain insight into the variation of base composition (GC, guanine + cytosine %) among and within animal and plant chromosomes, and into functional correlates of GC. Absorbance profiles of routine preparations of DNA in CsCl are essentially GC histograms of fixed-length sequence fragments (≈ 15-100 kb). This correspondence has been amply illustrated by genome sequences obtained over the past 5 years. Both AUC and sequencing have now generated large amounts of data that can be jointly mined. The dialogue between these two approaches should render tractable some tenacious problems of CsCl profile analysis, such as the correct treatment of concentration dependence for heterogeneous DNA. We focus on how absorbance profiles of a species' DNA vary as one changes the scale of one's observation (molecular weight), and dissect this scale-dependence into the contributions from its two main sources (diffusion, sequence effects). Our understanding of heterogeneous DNA in CsCl gradients can profit from the comparison of results from AUC and whole-genome sequencing, and the insights gained should prompt more strategic AUC analyses of DNA.