The ability of bacteria and archaea to modulate metabolic process, defensive

response, and pathogenic capabilities depend on their repertoire of genes and

capacity to regulate the expression of them. Transcription factors (TFs) have

fundamental roles in controlling these processes. TFs are proteins dedicated to

favor and/or impede the activity of the RNA polymerase. In prokaryotes these

proteins have been grouped into families that can be found in most of the

different taxonomic divisions. In this work, the association between the

expansion patterns of 111 protein regulatory families was systematically

evaluated in 1351 non-redundant prokaryotic genomes. This analysis provides

insights into the functional and evolutionary constraints imposed on different

classes of regulatory factors in bacterial and archaeal organisms. Based on

their distribution, we found a relationship between the contents of some TF

families and genome size. For example, nine TF families that represent 43.7% of

the complete collection of TFs are closely associated with genome size; i.e., in

large genomes, members of these families are also abundant, but when a genome is

small, such TF family sizes are decreased. In contrast, almost 102 families

(56.3% of the collection) do not exhibit or show only a low correlation with the

genome size, suggesting that a large proportion of duplication or gene loss

events occur independently of the genome size and that various yet-unexplored

questions about the evolution of these TF families remain. In addition, we

identified a group of families that have a similar distribution pattern across

Bacteria and Archaea, suggesting common functional and probable coevolution

processes, and a group of families universally distributed among all the

genomes. Finally, a specific association between the TF families and their

additional domains was identified, suggesting that the families sense specific

signals or make specific protein-protein contacts to achieve the regulatory

roles.