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Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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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...
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Exon Recombination02:32

Exon Recombination

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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. 
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Gene Duplication and Divergence02:37

Gene Duplication and Divergence

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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...
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Gene Evolution - Fast or Slow?

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Convergent Evolution01:54

Convergent Evolution

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Evolution shapes the features of organisms over time, ensuring that they are suited for the environments in which they live. Sometimes, selection pressure leads to the rise of similar but unrelated adaptations in organisms with no recent common ancestors, a process known as convergent evolution.
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Related Experiment Video

Updated: Jun 3, 2025

Initiating Differentiation in Immortalized Multipotent Otic Progenitor Cells
12:17

Initiating Differentiation in Immortalized Multipotent Otic Progenitor Cells

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Repurposing of a gill gene regulatory program for outer-ear evolution.

Mathi Thiruppathy1, Lauren Teubner1, Ryan R Roberts1

  • 1Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Nature
|January 9, 2025
PubMed
Summary

The mammalian outer ear evolved using gene regulatory programs shared with fish gills. This research uncovers the evolutionary reuse of ancient genetic pathways for developing the outer ear from gill-like structures.

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Area of Science:

  • Evolutionary developmental biology
  • Comparative genomics
  • Mammalian evolution

Background:

  • The evolutionary origin of the mammalian outer ear is poorly understood due to the lack of fossil evidence for its cartilaginous structures.
  • Previous research has illuminated the evolution of the middle ear from fish jawbones, but the outer ear's development remains enigmatic.

Purpose of the Study:

  • To investigate the evolutionary origins of the mammalian outer ear, specifically whether it arose de novo or through the repurposing of ancestral developmental programs.
  • To identify shared genetic and regulatory mechanisms between the development of the outer ear and other vertebrate structures.

Main Methods:

  • Comparative single-nucleus multiomics analysis of human outer ear and zebrafish gills.
  • Identification and functional validation of conserved gene expression patterns and enhancers using transgenic approaches.
  • Single-cell multiomics of horseshoe crab book gills to explore invertebrate gill development programs.

Main Results:

  • Conserved gene expression and regulatory elements were identified between the human outer ear and zebrafish gills.
  • Transgenic experiments demonstrated conserved enhancer activity between human outer ear and fish gills, and vice versa.
  • A shared Distal-less homeobox (DLX)-mediated developmental program was found in vertebrate gills and horseshoe crab book gills.

Conclusions:

  • The mammalian outer ear likely evolved through the co-option of gene regulatory programs originally used for gill development in ancestral vertebrates.
  • Elements of an ancient invertebrate gill development program were repurposed sequentially to form vertebrate gills and subsequently the mammalian outer ear.