Transcription factor

Biology

Gene

Philosophy

Transcription (linguistics)

Computer science

Linguistics

Computational biology

Genetics

Nature Communications

TATA-box binding protein (TBP) is required for every single transcription event in archaea and eukaryotes. It binds DNA and harbors two repeats with an internal structural symmetry that show sequence asymmetry. At various times in evolution, TBP has acquired multiple interaction partners and different organisms have evolved TBP paralogs with additional protein regions. Together, these observations raise questions of what molecular determinants (i.e. key residues) led to the ability of TBP to acquire new interactions, resulting in an increasingly complex transcriptional system in eukaryotes. We present a comprehensive study of the evolutionary history of TBP and its interaction partners across all domains of life, including viruses. Our analysis reveals the molecular determinants and suggests a unified and multi-stage evolutionary model for the functional innovations of TBP. These findings highlight how concerted chemical changes on a conserved structural scaffold allow for the emergence of complexity in a fundamental biological process.

Molecular determinants underlying functional innovations of TBP and their impact on transcription initiation