Interactions between immune cell types facilitate the evolution of immune traits

Area of Science:

• Immunology
• Evolutionary Biology
• Genetics

Background:

• Natural selection requires heritable variation in fitness-affecting traits.
• Evolvability, the capacity to produce selectable variation, influences evolutionary rates.
• The sources of variation in immune traits, crucial for rapid evolution, are largely unknown.

Purpose of the Study:

• To investigate the sources of variation in immune traits and their impact on immune system evolvability.
• To determine how the modular organization of the immune system contributes to its evolutionary capacity.
• To identify genetic factors influencing immune cell frequencies and their evolutionary constraints.

Main Methods:

• Immune cell profiling in bone marrow of 54 genetically diverse mouse strains (Collaborative Cross).
• Polygenic analysis to identify genes associated with immune cell frequency variation.
• Examination of gene expression patterns, including cell-extrinsic (cyto-trans) effects.

Main Results:

• Immune cell frequency variation is polygenic, with many genes regulating cell-intrinsic functions (proliferation, migration, apoptosis).
• Identified 'cyto-trans' genes, expressed in one cell type but affecting another, are prevalent.
• Cyto-trans genes show weaker negative selection in vertebrates, suggesting increased robustness.

Conclusions:

• Immune system modularity, particularly through cyto-trans interactions, enhances evolvability by allowing variation with less detriment.
• Interactions between immune components create a phenotypic space that facilitates adaptive evolution.
• This modularity is a key factor in the evolution of complex biological systems like the immune system.