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bioRxiv · 10.64898/2026.04.08.717362

Early evolution of the prokaryotic transcription factor repertoire

Singh, I. R.·Dubey, A.·Seshasayee, A. S. N.
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Abstract

Transcription initiation is regulated by proteins called transcription factors (TFs). Though TFs help determine phenotype across the tree of life, they are nonessential for minimal cellular life and are often absent in endosymbiotic and parasitic organisms. Given this and the idea that it is a certain level of organism complexity that calls for specific transcription regulation, we traced the evolutionary history of TF repertoire on a bacterio-archaeal tree of life using a dataset of [~]500,000 TFs, grouped into [~]1,700 orthologous groups (OGs) across [~]3,000 species. The most ancestral prokaryotes encoded multiple TFs. Going by known extant functions of these TFs, they possibly regulated sugar-fermentation metabolism, sensed overall metabolic state and redox, responded to DNA damage or bound metals; many of which are consistent with some reconstructions of ancestral gene pools and physiologies. The number of TFs as well as their superfamily-level diversity, through evolutionary history, matches expectations against genome size derived from extant bacteria, suggesting pre-LUCA diversification of TF sequence families. Emergence of new TFs along the phylogeny largely followed a smooth cumulative distribution curve, suggesting steady innovation, early in prokaryote evolution, in contrast to eukaryotes, in which a majority of TF families emerged in a burst manner at the ancestors of multicellular lineages. Gains of TFs late in prokaryotic evolution predominantly featured recycling of protein families discovered elsewhere in the prokaryotic tree, consistent with the dominance of horizontal gene transfer in these organisms. We speculate on the difference between the evolutionary trajectory of prokaryotic TF repertoire and compare it with the eukaryotic TF repertoire trajectory. This helps us in understanding the manner in which their TF repertoires have evolved in two different super-kingdoms. The difference between the evolutionary dynamics of TF-repertoires might be due to how complexity is envisioned in these two different kingdoms.

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Singh, I. R., Dubey, A., Seshasayee, A. S. N.. 2026-04-11. Early evolution of the prokaryotic transcription factor repertoire. https://doi.org/10.64898/2026.04.08.717362

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