Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Gene Evolution - Fast or Slow?

Gene 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...

Gene Evolution - Fast or Slow?

Gene Evolution - Fast or Slow?

From DNA to Protein

From DNA to Protein

The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...

Genome Copying Errors

Genome Copying Errors

DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.

Multi-species Conserved Sequences

Multi-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...

Exon Recombination

Exon 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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Mapping RNA structure assembly and remodeling in biomolecular condensates.

bioRxiv : the preprint server for biology·2026

Same author

Resolving human neuronal herpesvirus reactivation via petabase-scale association studies.

bioRxiv : the preprint server for biology·2026

Same author

Multi-site DMS probing reveals higher-order structure of RNA-protein complexes in living cells.

Molecular cell·2026

Same author

Author Correction: Phenome-wide analysis of copy number variants in 470,727 UK Biobank genomes.

Nature·2026

Same author

Precision Diagnosis in APOL1 Kidney Disease With the p.N264K M1 Protective Variant.

JAMA network open·2026

Same author

Ubiquitous low-energy RNA fluctuations and energetic coupling measured by chemical probing.

bioRxiv : the preprint server for biology·2026

Search research articles

Related Experiment Video

Updated: Dec 18, 2025

Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers

Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers

Published on: June 24, 2019

Natural Selection Shapes Codon Usage in the Human Genome.

Ryan S Dhindsa¹, Brett R Copeland², Anthony M Mustoe³

¹Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, New York, NY 10032, USA.

American Journal of Human Genetics

|June 10, 2020

Summary

Natural selection optimizes synonymous codon usage in the human genome, impacting gene function and potentially contributing to disease. This study reveals that synonymous mutations play a significant, underappreciated role in human genetic variation.

Keywords:

RVIS codon optimality codon usage conservation constraint intolerance population genetics synGERP synRVIS synonymous mutations

More Related Videos

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

In Vivo Modeling of the Morbid Human Genome using Danio rerio

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

Related Experiment Videos

Last Updated: Dec 18, 2025

Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers

Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers

Published on: June 24, 2019

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

In Vivo Modeling of the Morbid Human Genome using Danio rerio

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

Area of Science:

Genomics
Molecular Biology
Human Genetics

Background:

Synonymous codon usage influences translational efficiency and mRNA stability in model systems.
The role of natural selection in shaping human codon content for translation optimization remains unclear.
Synonymous mutations are often overlooked as disease contributors, except when affecting splicing.

Purpose of the Study:

To investigate whether natural selection optimizes codon content in the human genome.
To explore the impact of synonymous variation on gene function and human disease.
To quantify gene-level constraint on synonymous variation.

Main Methods:

Analysis of genetic sequencing data from nearly 200,000 individuals.
Development of intolerance metrics to assess constraint on synonymous variation.
Investigation of codon optimality in specific genes, including BRCA1.

Main Results:

Clear evidence that natural selection optimizes codon content in the human genome.
Dosage-sensitive, DNA-damage-response, and cell-cycle-regulated genes show particular intolerance to synonymous variation.
Reduced codon optimality in BRCA1 can impair its function.

Conclusions:

Synonymous codon usage is under natural selection in humans.
Synonymous mutations represent an underappreciated factor in human genetic variation and disease.
Constraint on synonymous variation is significant in functionally important genes.