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In Vitro Microfluidic Disease Model to Study Whole Blood-Endothelial Interactions and Blood Clot Dynamics in Real-Time
Published on: May 24, 2020
Step-by-step evolution of vertebrate blood coagulation.
1Department of Chemistry and Biochemistry and Molecular Biology, University of California, San Diego, La Jolla, CA 92093-0314, USA. rdoolittle@ucsd.edu
Cold Spring Harbor Symposia on Quantitative Biology
|August 12, 2009
Summary
The evolution of blood clotting factors reveals their gradual acquisition throughout vertebrate history. Key mammalian clotting factors emerged progressively, with some absent even in egg-laying mammals, highlighting complex evolutionary pathways.
Area of Science:
- Evolutionary biology
- Genomics
- Biochemistry
Background:
- Blood coagulation is a complex process involving over two dozen genetically encoded factors in mammals.
- Whole-genome sequencing facilitates the reconstruction of complex trait evolution, such as blood clotting.
- Understanding the evolutionary history of clotting factors provides insights into vertebrate adaptation.
Purpose of the Study:
- To investigate the evolutionary emergence and presence of mammalian blood clotting factors across vertebrate lineages.
- To identify the point in vertebrate evolution where key blood clotting factors first appeared or were lost.
- To compare gene inventories of protochordates and various nonmammalian vertebrates for clotting factor orthologs.
Main Methods:
- Examined whole-genome sequences from two protochordates (sea squirt, amphioxus) and seven nonmammalian vertebrates.
- Searched for approximately 20 genes associated with mammalian blood clotting.
- Utilized comparative genomics to identify genuine orthologs across species.
Main Results:
- No genuine orthologs for mammalian blood clotting factors were found in protochordate genomes.
- Jawless fish possess genes for fibrinogen to fibrin conversion but lack essential thrombin activators.
- Fish generally lack contact factor proteases, which first appear in tetrapods.
- The complete set of human clotting factors is present in marsupials (opossum), but not in egg-laying mammals (platypus).
Conclusions:
- Blood clotting factor evolution is a stepwise process, with factors appearing gradually throughout vertebrate evolution.
- The evolutionary trajectory of clotting factors varies significantly across different vertebrate groups.
- The study highlights the incomplete complement of clotting factors in basal vertebrates and even some mammals, underscoring the complexity of hemostasis evolution.
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