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Updated: Jul 5, 2026

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Published on: March 18, 2020
Rapid evolution by positive Darwinian selection in T-cell antigen CD4 in primates
Zhengdong D Zhang1, George Weinstock, Mark Gerstein
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
The CD4 protein, crucial for immune response and HIV/SIV infection, evolves rapidly due to positive selection. This selection pressure, particularly on its surface where viruses bind, is linked to SIV infection in primates.
Area of Science:
- Evolutionary biology
- Immunology
- Virology
Background:
- CD4 is a key glycoprotein in immune response and HIV/SIV lifecycle.
- CD4 exhibits faster evolution than most mammalian genes, suggesting strong selective pressures beyond simple relaxation of purifying selection.
Purpose of the Study:
- Investigate the evolutionary dynamics of CD4.
- Identify regions and sites under positive selection.
- Explore the relationship between CD4 evolution, structure, and SIV interaction.
Main Methods:
- Comparative genomic analysis of orthologous human and mouse CD4 genes.
- Reconstruction of ancestral primate CD4 coding sequences.
- Tertiary structure modeling of ancestral and extant CD4 sequences.
- Structural mapping of positively selected sites.
Main Results:
- Identified significant positive selection acting on specific CD4 codon sites.
- Positively selected sites are located on the D1 domain surface, the binding site for SIV gp120.
- Ancestral CD4 sequences from SIV-infected primate lineages show greater variation in electrostatic charge and CD4-gp120 complementarity.
Conclusions:
- Positive selection on CD4 in primates is likely driven by SIV infection.
- Evolutionary changes in CD4 sequence and structure are linked to its interaction with immunodeficiency viruses.
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