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Related Experiment Videos

Ancient origin of human complement factor H

J Krushkal1, C Kemper, I Gigli

  • 1Research Center for Human Genetics, Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center, 2121 Holcombe Boulevard, Houston, TX 77030, USA.

Journal of Molecular Evolution
|November 3, 1998
PubMed
Summary
This summary is machine-generated.

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The alternative complement pathway protein factor H (FH) has an ancient evolutionary origin, predating the classical pathway protein C4b-binding protein alpha (C4bpalpha). This supports the theory that the alternative pathway is evolutionarily older.

Area of Science:

  • Immunology
  • Evolutionary Biology
  • Biochemistry

Background:

  • The human complement system comprises two main pathways: the classical and alternative pathways.
  • Factor H (FH) is a key regulator of the alternative pathway, while C4b-binding protein alpha (C4bpalpha) regulates the classical pathway.
  • Homologous proteins in different species offer insights into evolutionary history.

Purpose of the Study:

  • To investigate the evolutionary history of human factor H (FH) and C4bpalpha.
  • To compare the evolutionary origins of the alternative and classical complement pathways.
  • To establish the evolutionary relationship between human complement proteins and those from barred sand bass (P. nebulifer) and C. elegans.

Main Methods:

  • Phylogenetic tree inference using individual short consensus repeats (SCRs).

Related Experiment Videos

  • Analysis of sequence divergence among repeats from different genes.
  • Comparative analysis of complement proteins across species.

    • Main Results:

    • Phylogenetic analysis indicates human FH shares a closer evolutionary relationship with complement components from P. nebulifer and C. elegans than C4bpalpha.
    • This suggests FH, an alternative pathway component, has an ancient origin.
    • C4bpalpha, a classical pathway component, likely arose later through gene duplication.
    • Sand bass proteins SBP1 and SBCRP-1 show very recent divergence.

    Conclusions:

    • The alternative complement pathway, represented by FH, is evolutionarily older than the classical pathway, represented by C4bpalpha.
    • Gene duplication events played a role in the evolution of complement system components.
    • Comparative genomics provides evidence for the evolutionary history of immune system proteins.