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An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
Coevolution reveals a network of human proteins originating with multicellularity
Alexandr Bezginov1, Gregory W Clark, Robert L Charlebois
1Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Molecular Biology and Evolution
|September 15, 2012
Summary
The human protein coevolution network reveals two distinct subnetworks: one ancient and one animal-specific. The animal subnetwork, enriched in cell communication and division proteins, is linked to diseases like cancer and ciliopathies.
Area of Science:
- Evolutionary biology
- Systems biology
- Genomics
Background:
- Protein interaction networks are crucial for biological systems and organismal development.
- Dysfunctional interactions can lead to disease by disrupting homeostasis.
- Understanding the evolution of these interactions is key to understanding disease origins.
Purpose of the Study:
- To investigate the evolutionary history of protein interactions.
- To construct and analyze the human protein coevolution network.
- To identify links between protein coevolution, multicellularity, and disease.
Main Methods:
- Derived the human protein coevolution network using the MatrixMatchMaker algorithm and the Orthologous MAtrix (OMA) database.
- Utilized protein orthologs from 103 eukaryotic genomes.
- Annotated the network with protein-protein interaction data, functional data, evolutionary rates, and emergence dates.
Main Results:
- Clustering partitioned the coevolution network into ancient eukaryotic and recent animal-specific subnetworks.
- The animal subnetwork is enriched for proteins involved in cell-cell communication and cell division.
- Proteins in the animal subnetwork are implicated in ciliopathies and cancer, suggesting a functional link.
Conclusions:
- The evolution of multicellularity involved the recruitment of ancient ciliary functions.
- Protein coevolution patterns reflect distinct functional roles in ancient eukaryotes versus animals.
- The identified animal-specific protein network is strongly associated with human diseases, particularly ciliopathies and cancer.
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