Related Experiment Video
Updated: Jun 23, 2026
07:28
Identification of Functionally-Relevant Lentivirus Integration Sites in an Insertional Mutagenesis Cell Library
Published on: January 10, 2025
Pervasive cryptic selection in the human noncoding genome
Biorxiv : the Preprint Server for Biology
|June 22, 2026
Summary
Cryptic selection, where mutations are under negative selection but not detected by conservation, is pervasive in the human genome. This evolutionary dynamic challenges traditional methods, revealing more genome-wide constraint than previously estimated.
Area of Science:
- Evolutionary genetics
- Comparative genomics
- Human population genetics
Background:
- Traditional evolutionary genetics assumes conserved sequences are under negative selection, while non-conserved ones evolve neutrally.
- Comparative genomics estimates ~5% of the human genome experiences negative selection, but functional turnover may hide other selected sites.
- The extent of this 'cryptic' or hidden negative selection remains largely unknown.
Purpose of the Study:
- To develop a statistical method for detecting cryptic selection in human polymorphism data.
- To quantify the prevalence and impact of cryptic selection on genome-wide constraint estimates.
- To highlight the limitations of conservation-based approaches in evolutionary genetics.
Main Methods:
- Developed a novel statistical test to identify cryptic selection using human polymorphism data.
- Applied the test to simulated data to assess detection power based on selection proportion, sequence length, and sample size.
- Analyzed polymorphism data from the 1000 Genomes Project, comparing functional and neutral regions.
Main Results:
- Cryptic selection significantly shapes the site frequency spectrum (SFS).
- Pervasive signals of cryptic selection were detected in putatively functional noncoding regions, even after removing highly conserved sites.
- Estimated that at least 7% of the human genome is under negative selection, exceeding previous conservation-based estimates.
Conclusions:
- Cryptic selection is widespread in the human genome and has been underestimated by conservation-based methods.
- Functional turnover in noncoding regions contributes significantly to genome-wide constraint.
- Future evolutionary analyses must incorporate functional turnover to accurately identify neutral variants.
More Related Videos
Related Concept Videos
02:51Multi-species Conserved Sequences
Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
02:05Gene Evolution - Fast or Slow?
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
02:05Gene Evolution - Fast or Slow?
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
01:21Frequency-dependent Selection
When the fitness of a trait is influenced by how common it is (i.e., its frequency) relative to different traits within a population, this is referred to as frequency-dependent selection. Frequency-dependent selection may occur between species or within a single species. This type of selection can either be positive—with more common phenotypes having higher fitness—or negative, with rarer phenotypes conferring increased fitness.Positive Frequency-Dependent SelectionIn positive...
02:07Organization of Genes
Overview
02:32Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.