Positive Selection on Mammalian Immune Genes-Effects of Gene Function and Selective Constraint

Area of Science:

• Evolutionary biology
• Immunology
• Genomics

Background:

• Genome-wide studies reveal immune genes are often under positive selection across taxa.
• Factors determining positive selection on specific immune genes remain largely unknown.
• Understanding these factors is crucial for comprehending immune system evolution.

Purpose of the Study:

• To investigate determinants of positive selection in mammalian immune genes.
• To assess the roles of gene function, expression, protein interactions, and selective constraint.
• To compare selection pressures on different immune gene categories, including pattern recognition receptors (PRRs).

Main Methods:

• Compiled a dataset of over 1,100 mammalian immune genes, categorized by function.
• Analyzed selection pressures using data from rodent models.
• Quantified rates of positive selection and selective constraint across gene categories.

Main Results:

• Cytokines, cytokine receptors, and cell surface proteins showed high rates of positive selection, comparable to PRRs.
• These categories exhibited three times the rate of positive selection compared to non-immune genes.
• Lower selective constraint partly explained the high selection on cytokines/cell surface proteins, but gene function remained a key driver.

Conclusions:

• Gene function, particularly for cytokines and cell surface proteins, is a significant determinant of positive selection in immune genes.
• Processes beyond direct host-pathogen coevolution likely contribute to immune gene evolution.
• Findings have broad implications for understanding the evolutionary dynamics of the mammalian immune system.