Identifying branch-specific positive selection throughout the regulatory genome using an appropriate proxy neutral
Alejandro Berrio1, Ralph Haygood2, Gregory A Wray3
1Department of Biology, Duke University, Biological Sciences Building, 124 Science Drive, Durham, NC, 27708, USA. alebesc@gmail.com.
BMC Genomics
|May 15, 2020
Summary
A new method, adaptiPhy, enhances the detection of adaptive evolution in noncoding DNA. It improves the identification of positive selection in human accelerated elements, revealing that a quarter of these elements evolve under positive selection.
Area of Science:
- Evolutionary biology
- Genomics
- Bioinformatics
Background:
- Adaptive changes in cis-regulatory elements are key to evolution by natural selection.
- Identifying functional noncoding DNA is crucial for linking genotype to phenotype.
Purpose of the Study:
- To introduce adaptiPhy, a method for improved detection of directional selection in noncoding DNA.
- To provide a more sensitive and targeted characterization of selection across the genome.
Main Methods:
- Utilized ENCODE annotations for proxy neutral sequences.
- Applied adaptiPhy to human accelerated elements and open chromatin regions.
- Evaluated the impact of sequence length and branch count on test performance.
Main Results:
- adaptiPhy demonstrated utility in identifying selection in noncoding elements.
- Optimal lengths for query (150 bp–1 kb) and reference (3 kb) alignments were determined.
- The method successfully distinguished positive selection from neutral evolution and relaxation of constraint.
- Confirmed that 25% of non-coding Human Accelerated Elements show evidence of positive selection.
Conclusions:
- adaptiPhy offers significant improvements for detecting branch-specific directional selection in noncoding sequences.
- The method enhances the characterization of directional selection and neutral evolution genome-wide.
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