In this work, we describe a systematic comparative genomic analysis of
promiscuous domains in genomes of Bacteria and Archaea. A quantitative measure
of domain promiscuity, the weighted domain architecture score (WDAS), was used
and applied to 1317 domains in 1320 genomes of Bacteria and Archaea. A
functional analysis associated with the WDAS per genome showed that 18 of 50
functional categories were identified as significantly enriched in the
promiscuous domains; in particular, small-molecule binding domains, transferases
domains, DNA binding domains (transcription factors), and signal transduction
domains were identified as promiscuous. In contrast, non-promiscuous domains
were identified as associated with 6 of 50 functional categories, and the
category Function unknown was enriched. In addition, the WDASs of 52 domains
correlated with genome size, i.e., WDAS values decreased as the genome size
increased, suggesting that the number of combinations at larger domains
increases, including domains in the superfamilies Winged helix-turn-helix and
P-loop-containing nucleoside triphosphate hydrolases. Finally, based on
classification of the domains according to their ancestry, we determined that
the set of 52 promiscuous domains are also ancient and abundant among all the
genomes, in contrast to the non-promiscuous domains. In summary, we consider
that the association between these two classes of protein domains (promiscuous
and non-promiscuous) provides bacterial and archaeal cells with the ability to
respond to diverse environmental challenges.