Friday, August 07, 2009

The genome, more than coding   posted by Razib @ 8/07/2009 06:12:00 PM

Evolutionary Processes Acting on Candidate cis-Regulatory Regions in Humans Inferred from Patterns of Polymorphism and Divergence. Let me just jump to the final paragraph since that's probably what most readers are curious about:
Our analysis of human polymorphism and divergence in conserved non-coding sites suggests that the evolution of candidate cis-regulatory regions is often driven by both positive and negative selection. Our findings reinforce the idea that the non-coding portion of our genome has an important functional and evolutionary role, and suggest that patterns of natural selection in non-coding DNA are often distinct from that of protein-coding regions. Many of the adaptive changes in candidate cis-regulatory regions might have occurred near genes expressed in the fetal brain, supporting the hypothesis that the evolution of the developing brain may be largely attributable to changes in gene regulation. Our results add to the increasing evidence that non-coding DNA is not all selectively neutral, and that selection on candidate cis-regulatory regions has played an important role throughout hominid evolution.

Gene regulation has of course been one possible solution to how humans can be so phenotypically different from chimpanzees despite close sequence level identity.

Related: Dissecting the regulatory differences between human and chimp.

Labels: ,

Thursday, February 26, 2009

Epigenetics and gene structures   posted by p-ter @ 2/26/2009 07:40:00 PM

Following up on this previous post on epigentics, I thought I'd point to a couple nice examples of using epigenetic information to obtain insight into basic biology.

The first is, I think it's fair to say, a landmark paper identifying a set of over a thousand likely functional non-coding RNAs in mouse cell lines. The approach used here was epigenetic: the authors generated genome-wide maps of chromatin modifications known to mark promoters and transcribed regions, and screened out all the regions of the genome already known to be transcriptionally active. This left them with a set of putatively functional transcripts, which tended to be highly evolutionarily conserved (indicating function), and many of which they confirmed via other means to be novel long non-coding RNAs.

The second is a nice paper demonstrating that one of the same epigentic marks used above to identify transcribed regions is present, in humans, mice, and nemotodes, preferentially on exons (rather than on the entirety of the transcribed region). As this mark is present only in genes that are being transcribed, the authors conclude that it is placed in conjunction with transcription, and likely in conjunction with splicing. They speculate about the role that this mark could play in gene regulation, but in general, this paper raises many more interesting questions than can currently be answered.

Labels: ,

Saturday, December 20, 2008

Transcription around promoters   posted by p-ter @ 12/20/2008 05:38:00 PM

A number of papers out this week (summarized here) notice, using various technologies, the presence of extensive transcription off both DNA strands around active promoters. A figure from one of the papers is above--note the peak in transcription from the sense strand just downstream of the transcription start site (TSS), and the peak in anti-sense transcription just upstream of the TSS. This is an interesting observation, and an example of the unexpected things you can see with new technologies, but no one is exactly sure what to make of it--it could just be the transcriptional machinery being a bit sloppy.

Labels: ,