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Related Experiment Videos

Did myocilin evolve from two different primordial proteins?

Arijit Mukhopadhyay1, Arnab Gupta, Saibal Mukherjee

  • 1Indian Institute of Chemical Biology, Human Genetics & Genomics Division, Jadavpur, Kolkata, India.

Molecular Vision
|July 27, 2002
PubMed
Summary

Molecular evolution suggests myocilin arose from gene fusion, potentially explaining its link to primary open-angle glaucoma. This study investigated myocilin

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Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Genetics

Background:

  • Myocilin is a 57 kDa glycoprotein implicated in primary open-angle glaucoma.
  • Its biological function remains poorly understood.
  • Sequence homology suggests N- and C-termini relate to myosin and olfactomedin, respectively.

Purpose of the Study:

  • To investigate the molecular evolution of myocilin.
  • To understand the evolutionary origins of myocilin's distinct domains.
  • To explore the relationship between myocilin's structure and its association with glaucoma.

Main Methods:

  • Sequence alignment and database searches across species.
  • Secondary structure analysis using PSIPRED.
  • Disulfide bond prediction using CYSPRED.

Related Experiment Videos

  • Putative motif identification via ScanProsite.
  • Phylogenetic analysis of mammalian myocilins.

    • Main Results:

    • Homology to myocilin's termini found in various species, with Xenopus laevis showing broader homology.
    • Conserved amino acids and functional motifs identified between homologous protein sets.
    • Myocilin exhibits distinct secondary structures: alpha-helical N-terminus and beta-sheet/turn C-terminus.
    • Phylogenetic analysis shows closer relationships between rat and mouse myocilins.

    Conclusions:

    • Myocilin likely evolved from the fusion of at least two distinct genes.
    • Mutations in glaucoma-associated myocilin exons (1 and last) support the gene fusion hypothesis.
    • Evolutionary insights may clarify myocilin's role in mammalian biology and disease.