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

Conserved Binding Sites

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...

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?

Evolutionary Relationships through Genome Comparisons

Evolutionary Relationships through Genome Comparisons

Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...

Conservation of Protein Domains Over Different Proteins

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...

Protein Organization

Protein Organization

Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....

You might also read

Related Articles

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

Sort by

Same author

Targeting immune cells in the aged brain reveals that engineered cytokine IL-10 enhances neurogenesis and improves cognition.

Immunity·2026

Same author

Author Correction: Streptomyces produce a diphtheria toxin-like exotoxin that targets insects.

Nature microbiology·2026

Same author

Streptomyces produce a diphtheria toxin-like exotoxin that targets insects.

Nature microbiology·2026

Same author

Widespread gene fusion artifacts in helminth genome annotations.

BMC genomics·2026

Same author

Targeting immune cells in the aged brain reveals that engineered cytokine IL-10 enhances neurogenesis and improves cognition.

Immunity·2026

Same author

Age-related microbiome metabolites alter RNA splicing and chromatin accessibility in the brain.

bioRxiv : the preprint server for biology·2025

Search research articles

Related Experiment Video

Updated: Mar 9, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

Lineage-specific mutational clustering in protein structures predicts evolutionary shifts in function.

Jeremy Adams¹, Michael J Mansfield¹, Daniel J Richard¹

¹Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

Bioinformatics (Oxford, England)

|January 6, 2017

Summary

We developed a method to detect spatially clustered mutations in protein evolution, identifying over 19,000 lineages with significant clusters. This approach reveals functional shifts and new candidates for experimental study in protein families.

More Related Videos

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Identification and Classification of Position-specific GABA_A Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

Related Experiment Videos

Last Updated: Mar 9, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Identification and Classification of Position-specific GABA_A Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

Area of Science:

Evolutionary biology
Structural biology
Bioinformatics

Background:

Spatially clustered mutations in proteins often indicate positive selection for new functions, particularly in cancer oncoproteins.
Previous methods focused on pairwise comparisons, leaving the utility for phylogenetic analysis unexplored.

Purpose of the Study:

To adapt and extend spatial substitution clustering methods for phylogenetic branch analysis.
To investigate the capacity of this approach to identify historical functional shifts in protein families.

Main Methods:

Implemented and enhanced the P3D statistic for detecting spatially clustered substitutions on phylogenetic branches.
Analyzed 423,690 vertebrate protein family branches from 9,261 families.
Examined enrichment of clusters in ligand-binding sites and specific protein families (e.g., C2H2 transcription factors, protein kinases).

Main Results:

Identified 19,607 lineages across 5,362 protein families with significant spatial substitution clustering (P3D < 0.01).
Spatially clustered substitutions were enriched in ligand-binding residues and specific protein families.
Detected functional shifts and new interactions in ancient adaptations of proteins like SLC7A2, PTEN, and SNAP25.

Conclusions:

Lineage-specific, spatially clustered substitutions are valuable indicators of functional shifts in protein evolution.
The developed method successfully identifies historical functional changes and provides new candidates for experimental validation.