Analysis of Genetic Variation Indicates DNA Shape Involvement in Purifying Selection

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• Noncoding DNA sequences are crucial for gene expression and regulation.
• Transcription factors (TFs) use both DNA sequence and shape for binding specificity.
• Previous work linked DNA shape changes from single nucleotide polymorphisms (SNPs) to altered TF binding.

Purpose of the Study:

• To test the hypothesis that local DNA shape within and around TF binding sites is under evolutionary selection pressure.
• To investigate the role of DNA shape in the evolution of regulatory elements.

Main Methods:

• Analysis of SNP data from 216 natural strains of Drosophila melanogaster.
• Comparison of SNPs in functional versus nonfunctional regions of experimentally validated cis-regulatory modules (CRMs).
• Utilized DNase I accessibility data to identify putative CRMs for broader genome-wide analysis.

Main Results:

• SNPs in functional CRM regions showed smaller DNA shape variations compared to nonfunctional regions.
• SNPs with higher minor allele frequencies were associated with smaller DNA shape variations.
• These findings were consistent across both validated and putative CRMs.

Conclusions:

• Common SNPs in functional regulatory regions tend to maintain DNA shape.
• SNPs that significantly alter DNA shape are likely eliminated by purifying selection.
• DNA shape is an important factor under evolutionary constraint in regulatory DNA.