Most studies of molecular evolution focus on protein-coding sequences. It seems that the regulatory sequences are overlooked. How do regulatory sequences evolve? How do they control spatial and temporal gene expression?
These are big, open-ended questions with no clear answers.
The short answer to how they evolve is that they evolve like all other sequences, under the standard evolutionary forces of mutation, genetic drift, natural selection, recombination, etc. The mode of selection on regulatory sequences is either thought to be selective constraint or stabilizing selection. See the citeulike library I maintain on this topic here to get a flavor of the diversity or results on regulatory evolution.
The regulatory code question is the/a $64,000 question in post-genomic biology. There is no general solution (yet) to decode the regulatory function of a sequence, and anyone who says there is IMO is over-stating their results or method.
quick PubMed search:
Bullaughey K. Changes in selective effects over time facilitate turnover of enhancer sequences. Genetics. 2011 Feb;187(2):567-82. Epub 2010 Nov 23. PubMed PMID: 21098721; PubMed Central PMCID: PMC3030497.
Crocker J, Potter N, Erives A. Dynamic evolution of precise regulatory encodings creates the clustered site signature of enhancers. Nat Commun. 2010 Oct 19;1:99. doi: 10.1038/ncomms1102. PubMed PMID: 20981027; PubMed Central PMCID: PMC2963808.
Hardison RC. Variable evolutionary signatures at the heart of enhancers. Nat Genet. 2010 Sep;42(9):734-5. PubMed PMID: 20802475.
Lusk RW, Eisen MB. Evolutionary mirages: selection on binding site composition creates the illusion of conserved grammars in Drosophila enhancers. PLoS Genet. 2010 Jan 22;6(1):e1000829. PubMed PMID: 20107516; PubMed Central PMCID: PMC2809757.
Borok MJ, Tran DA, Ho MC, Drewell RA. Dissecting the regulatory switches of development: lessons from enhancer evolution in Drosophila. Development. 2010 Jan;137(1):5-13. Review. PubMed PMID: 20023155; PubMed Central PMCID: PMC2796927.
Moses AM. Statistical tests for natural selection on regulatory regions based on the strength of transcription factor binding sites. BMC Evol Biol. 2009 Dec 9;9:286. PubMed PMID: 19995462; PubMed Central PMCID: PMC2800119.
Ho MC, Johnsen H, Goetz SE, Schiller BJ, Bae E, Tran DA, Shur AS, Allen JM, Rau C, Bender W, Fisher WW, Celniker SE, Drewell RA. Functional evolution of cis-regulatory modules at a homeotic gene in Drosophila. PLoS Genet. 2009 Nov;5(11):e1000709. Epub 2009 Nov 6. PubMed PMID: 19893611; PubMed Central PMCID: PMC2763271.
Crocker J, Tamori Y, Erives A. Evolution acts on enhancer organization to fine-tune gradient threshold readouts. PLoS Biol. 2008 Nov 4;6(11):e263. PubMed PMID: 18986212; PubMed Central PMCID: PMC2577699.
I would add another paper here: Science. 2010 May 21;328(5981):1036-40. Epub 2010 Apr 8. Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Schmidt D, Wilson MD, Ballester B, Schwalie PC, Brown GD, Marshall A, Kutter C, Watt S, Martinez-Jimenez CP, Mackay S, Talianidis I, Flicek P, Odom DT.
But as Casey says, there are many open questions and methodological limitations that are being worked on.
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