Thanks, Clayton, for your reply and for the reference. I'll read the paper with interest. The excerpts you pasted here suggest that nucleosomes are more than just mechanical and passive packaging devices. From an evolutive point of view, I guess that the current structure of nucleosomes was first 'established' to compress the increasing genomes and then the size of exons was somehow adjusted to fit their size due to the obtained advantages in controlling transcription and splicing...
Yes, I have read about that in Alberts et al.'s book, but I greatly appreciate this nice summary. You are right, my background is in CS, but I'm becoming more and more interested in so many computational features and concepts that are enclosed into cells!
Regarding evolution of exons, apparently they were 'first' and genes came later (in eucaryote cells) as aggregates of exons. As far as I know, this has been suggested by the correspondence between exons and protein domains. Is this consistent with exons that adapt their size to nucleosome capacity? They look like opposite evolution moves...
In addition to Vladimir's excellent points, I'd caution against putting too much weight into the idea that PolII pauses on exons preferentially in higher eukaryotes. At least in terms of ChIP-Seq datasets for PolII, I don't think this hypothesis can be well supported. In contrast, PolII enrichment at the 3' terminal exon of expressed genes is likely a general phenomenon.
Thanks for the new references and comments! Vladimir, the information in Alberts et al.'s book comes from the paper "Initial sequencing and analysis of the human genome" by the International Human Genome Sequencing Consortium (published in Nature 409:860-921, February 2001, doi: 10.1038/35057062, it is freely available) Figure 35a (page 896) shows the diagram that has been used in the book to establish the claim that originated my question. Table 21 in the same page gives the number 145 bp for the average size of exons for protein-coding genes in humans. And, actually, Figures 35b and 35c concern the length of introns (for humans, worms and flies), but (in sharp contrast with the exon case) no clear conclusion about a common average size for all of them can be established, i.e., the average size of introns depends more on the species than the average size of exons...
@Clayton- excellent post. Thanks for the citations from the Ast lab, and yes I agree that nucleosomal occupancy might affect PolII elongation rates without causing pausing per se. Introns themselves are hardly passive players here, though. The fact that enhancers often occur within them will lead to decreased nucleosomal occupancies within introns due to TF binding. In addition, additional regulatory elements promoting association with the nuclear matrix or nuclear envelope (often AT rich, and with lower nucleosomal conent) are probably exluded from exons.
Thanks everyone for this interesting discussion. I am wondering if we in certain diseases there is deletion of an exon and consequent alteration in nucleosome structure or shifting of nucleosome etc. Do we know any such disease?
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