Evolutionary analysis of transcription elongation factors reveals conserved and lineage-specific regulatory domains

In eukaryotes, transcription elongation factors (TEFs) associate with RNA Polymerase II (RNAPII) to facilitate gene expression and couple transcription to co-transcriptional processes, including chromatin regulation and RNA processing. To further our understanding of TEF biology, we developed a domain-centric analysis pipeline to perform a broad survey of 10 TEF orthologs—Paf1, Ctr9, Cdc73, Rtf1, Leo1, Spt4, Spt5, Spt6, Spn1, and Elf1—across the Tree of Life and analyze their evolutionary patterns in a structural context. We report evidence for all 10 TEFs being present in the last eukaryotic common ancestor, indicating that mechanisms of TEF-mediated transcription regulation are both ancient and conserved. However, some early-diverging eukaryotic clades exhibit signs of altered TEF domain composition. A comparative phylogenetic analysis highlighted conserved regions of TEFs that are detected in both metazoans and fungi and other regions that appear clade-specific, detected only in metazoans. These observations, together with additional insights generated from evolutionary rate covariation analysis, shed light on under-characterized aspects of TEFs, including domains for which functions have yet to be dissected.Transcription elongation factors associate with RNA Polymerase II to regulate gene expression and coordinate chromatin regulation and RNA processing. This study presents an evolutionary analysis of ten core transcription elongation factors and shows that all ten factors originated in the last eukaryotic common ancestor and display both conserved and lineage-specific domains.