Publication Date:
2009-03-17
Description:
The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein-binding affinity and phenotype. We developed an algorithm to measure constraint on the basis of similarity of DNA topography among multiple species, using hydroxyl radical cleavage patterns to interrogate the solvent-accessible surface area of DNA. This algorithm found that 12% of bases in the human genome are evolutionarily constrained-double the number detected by nucleotide sequence-based algorithms. Topography-informed constrained regions correlated with functional noncoding elements, including enhancers, better than did regions identified solely on the basis of nucleotide sequence. These results support the idea that the molecular shape of DNA is under selection and can identify evolutionary history.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749491/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749491/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parker, Stephen C J -- Hansen, Loren -- Abaan, Hatice Ozel -- Tullius, Thomas D -- Margulies, Elliott H -- R01 HG003541/HG/NHGRI NIH HHS/ -- R01 HG003541-03/HG/NHGRI NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):389-92. doi: 10.1126/science.1169050. Epub 2009 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics Program, Boston University, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286520" target="_blank"〉PubMed〈/a〉
Keywords:
Algorithms
;
Amino Acid Motifs
;
Base Sequence
;
Binding Sites
;
Conserved Sequence
;
DNA/*chemistry/genetics
;
Deoxyribonuclease I/metabolism
;
Early Growth Response Protein 1/genetics/metabolism
;
Evolution, Molecular
;
*Genome, Human
;
Humans
;
Mutant Proteins/metabolism
;
Nucleic Acid Conformation
;
Phenotype
;
Polymorphism, Single Nucleotide
;
Selection, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
