van Loo B and Bornberg-Bauer E
Enzyme sub-functionalization driven by regulation
EMBO reports, 2017

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The emergence of functional novelties in proteins during evolution has puzzled scientist
for many years. Most proposed models focus on repeated duplication-divergence cy-
cles. However, so far none of these studies address the entanglement of selection pres-
sures acting on transcription control and control of enzymatic activity, e.g. by metabo-
lites. In this issue of EMBO reports, Noda-Garcia et al describe two glutamate dehydro-
genase copies from Bacillus subtilis with very similar sequences and under two distinct
modes of activity control [1]. The functional divergence of these two enzymes during
evolution is driven by an interlinked combination of differences between their enzyme
properties and the transcriptional regulation, or lack thereof, that they are under. This
paper thus illuminates another level of complexity in molecular evolution that may help
understand the hitherto unexplained co-existence of paralogous genes that at first sight
appear to be functionally redundant.