Genetic plasticity of V genes under somatic hypermutation: statistical analyses using a new resampling-based...

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Somatic hypermutation (SHM) is crucial for generating antibody diversity.
• Previous research suggested sequence-specific mutation in immunoglobulin variable (V) genes, favoring complementarity-determining regions (CDRs).

Purpose of the Study:

• To develop a novel statistical method for analyzing genetic plasticity in V genes and V gene families.
• To identify factors influencing mutational differences between gene regions and quantify selection strength.
• To compare SHM patterns across species and investigate its evolutionary origins.

Main Methods:

• Developed a new resampling-based methodology for statistical analysis of genetic plasticity.
• Analyzed codon usage and mutability patterns in immunoglobulin V genes.
• Compared human and sheep immunoglobulin sequences, as well as human TCR V(beta) sequences.

Main Results:

• Immunoglobulin V genes exhibit distinct codon usage, though not fully optimized for SHM.
• Mutability patterns are largely conserved across species, with notable exceptions like sheep.
• Human TCR V(beta) sequences share mutability patterns with immunoglobulins, suggesting shared evolutionary history or functional overlap.

Conclusions:

• Somatic hypermutation likely emerged early in immune system evolution and is conserved across species.
• SHM plays an essential role in generating the antibody repertoire.
• The findings support a shared evolutionary origin or functional convergence of hypermutation mechanisms in immunoglobulins and T-cell receptors.