Related Experiment Video
Updated: May 12, 2026
08:35
Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
Published on: June 24, 2021
Testing for natural selection in human exonic splicing regulators associated with evolutionary rate shifts
Rodrigo F Ramalho1, Sahar Gelfman, Jorge E de Souza
1Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, 05508-900, Brazil. rfrusp@gmail.com
Journal of Molecular Evolution
|March 27, 2013
Summary
Slightly harmful genetic variations (polymorphisms) affecting exonic splicing silencers (ESSs) in essential gene regions are rare. Evolution favors inhibiting splicing signals, suggesting a common origin for exon skipping.
Area of Science:
- Evolutionary genetics
- Molecular biology
- Bioinformatics
Background:
- Exonic splicing silencers (ESSs) are crucial regulatory elements influencing gene expression.
- While ESSs in constitutive exons are under negative selection, the impact of deleterious polymorphisms on these regulators is poorly understood.
Purpose of the Study:
- To investigate the evolutionary impact of slightly deleterious polymorphisms on exonic splicing regulators (ESRs).
- To compare evolutionary patterns of ESRs in constitutive versus alternative exons.
- To explore the role of ESRs in the evolution of exon skipping.
Main Methods:
- Utilized a modified McDonald-Kreitman test to analyze human polymorphisms and human/rhesus substitutions.
- Focused analysis on exonic splicing regulators (ESRs) within constitutive and alternative exons.
- Compared evolutionary patterns between ESRs in constitutive exons and those involved in constitutive-to-skipped exon transitions.
Main Results:
- Observed a depletion of substitutions and an enrichment of single nucleotide polymorphisms (SNPs) linked to ESS gain in constitutive exons.
- Identified similar evolutionary patterns in ESRs previously implicated in the transition from constitutive to skipped exons during mammalian evolution.
- Found evidence suggesting that the evolution of exon skipping in mammals is more often driven by splicing signal inhibition than promotion.
Conclusions:
- Deleterious polymorphisms affecting ESSs in constitutive exons are likely purged by negative selection.
- The evolutionary trajectory from constitutive to skipped exons in mammals appears to favor the inhibition of splicing signals.
- Findings support the hypothesis of a constitutive origin for exon skipping and highlight the antagonistic roles of splicing regulatory elements.
Related Concept Videos
02:32Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...
02:18Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
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...
01:07Speciation Rates
Overview
02:02Cis-regulatory Sequences
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...