Ruminant-specific retrotransposons shape regulatory evolution of bovine immunity

Area of Science:

• Genomics
• Immunology
• Evolutionary Biology

Background:

• Transposable elements (TEs) are increasingly recognized for their role in gene regulation and evolutionary variation.
• Their contribution to ruminant genomes, particularly in immune responses, remains largely unexplored.
• Understanding these elements is crucial for livestock improvement and disease resistance.

Purpose of the Study:

• To investigate the role of lineage-specific TEs in regulating the type II interferon (IFN) response in cattle.
• To identify specific TEs that function as IFN-inducible enhancers in bovine cells.
• To determine if polymorphic TE insertions contribute to immune gene regulation in modern cattle populations.

Main Methods:

• Epigenomic profiling of the type II interferon response in bovine cells.
• CRISPR-Cas9 gene editing to assess the function of TE-derived enhancers.
• Population genomic analysis of TEs in 38 cattle individuals.

Main Results:

• Thousands of ruminant-specific TEs, including MER41_BT and Bov-A2, were identified as potential IFN-inducible enhancers.
• CRISPR knockout experiments confirmed that TE-derived enhancers regulate key immune factors like IFNAR2 and IL2RB.
• Polymorphic TE insertions were found to potentially act as enhancers in contemporary cattle.

Conclusions:

• Lineage-specific TEs have significantly shaped the evolution of ruminant IFN responses.
• These TEs continue to influence immune gene regulation across cattle breeds and individuals.
• TE co-option is a recurrent evolutionary mechanism for regulating IFN-inducible gene expression across species.