Related Experiment Video

Updated: Aug 12, 2026

High-throughput Screening for Protein-based Inheritance in S. cerevisiae
08:12

High-throughput Screening for Protein-based Inheritance in S. cerevisiae

Published on: August 8, 2017

Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states

P Schaner1, N Richards, A Wadhwa

  • 1Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan, USA.

Nature Genetics
|March 10, 2001
PubMed

Insights

Familial Mediterranean fever (FMF) is linked to pyrin gene mutations. Evolutionary analysis suggests these mutations may have provided a selective advantage, driving pyrin

Area of Science:

  • Evolutionary biology
  • Genetics
  • Molecular biology

Background:

  • Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder.
  • FMF is caused by mutations in the pyrin gene, with high allele frequencies suggesting a selective advantage.
  • The ret finger protein (rfp) domain of pyrin harbors most disease-causing mutations.

Purpose of the Study:

  • To investigate the evolutionary history of the pyrin gene, specifically its rfp domain, across primate species.
  • To determine if disease-associated amino acid positions in human pyrin are conserved or represent ancestral states in other primates.
  • To identify signatures of natural selection acting on the pyrin gene during primate evolution.

Main Methods:

  • Comparative sequence analysis of the pyrin rfp domain across primate lineages.
  • Identification of amino acid variations at disease-relevant positions.
  • Analysis of lineage-specific dN/dS ratios to detect positive selection.

Main Results:

  • Several amino acid positions associated with human FMF mutations were found to be wild-type in other primate species.
  • For some positions, human disease mutations represent a reversion to an ancestral amino acid state.
  • Episodic positive selection signatures were detected in pyrin, particularly within primate lineages.

Conclusions:

  • The pyrin gene has undergone functional evolution driven by selective pressures in humans and other primates.
  • High FMF allele frequencies in human populations may be a consequence of past selective advantages conferred by pyrin mutations.
  • Evolutionary analysis provides insights into the genetic basis and potential adaptive significance of FMF.

More Related Videos

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing07:24

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing

Published on: February 10, 2023

Following the Dynamics of Structural Variants in Experimentally Evolved Populations04:52

Following the Dynamics of Structural Variants in Experimentally Evolved Populations

Published on: February 3, 2023

Related Concept Videos

Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Synteny and Evolution02:31

Synteny and Evolution

John H. Renwick first coined the term “synteny” in 1971, which refers to the genes present on the same chromosomes, even if they are not genetically linked. The species with common ancestry tend to show conserved syntenic regions. Therefore, the concept of synteny is nowadays used to describe the evolutionary relationship between species.
Around 80 million years ago, the human and mice lineages diverged from the common ancestor. During the course of evolution, the ancestral chromosome underwent...
Gene Duplication and Divergence02:37

Gene Duplication and Divergence

The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was  generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.
Exon Recombination02:32

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 has three reading...
Point and Frameshift Mutations01:30

Point and Frameshift Mutations

Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...