Evolution of a polymorphic regulatory element in interferon-gamma through transposition and mutation.

Area of Science:

• Evolutionary genomics
• Molecular evolution
• Gene regulation

Background:

• Mammalian transposable elements possess regulatory elements capable of activating adjacent genes.
• Transposable elements may also relocate extrinsic transactivating DNA sequences to new genomic positions.
• The role of comobilized regulatory sequences in shaping gene regulatory networks is largely unexplored.

Purpose of the Study:

• To investigate the origin and evolution of regulatory elements within the human interferon-gamma promoter.
• To determine if transposable elements can comobilize functional DNA sequences.
• To understand the impact of such events on gene regulatory network evolution.

Main Methods:

• Identification and characterization of a polymorphic segment in the human interferon-gamma promoter.
• Sequence comparisons across nine primate species.
• Analysis of DNA-protein interactions to assess binding site functionality.

Main Results:

• An Alu element insertion, dated 22-34 million years ago, introduced two adjacent binding sites for NF-kappaB and NFAT into the interferon-gamma promoter.
• The inserted DNA segment, containing an intact NFAT binding site, was comobilized with the Alu element.
• The NF-kappaB binding ability evolved through post-insertion mutations, indicating a stepwise acquisition of function.

Conclusions:

• Retropseudogenes can comobilize intact regulatory sequences, influencing the evolution of gene regulatory networks.
• The findings support the hypothesis that transposable elements contribute to regulatory innovation.
• Further research is needed to quantify the extent to which these events have shaped genome evolution.