The role of domain shuffling in the evolution of signaling networks

Abstract

In a seminal paper entitled "Evolution and Tinkering," François Jacob affirmed that: "Novelties come from previously unseen association of old material. To create is to recombine" [Jacob F. (1977) Science 196:1161-1166]. In the 35 years that have passed since Jacob's insight, we have amassed enough data to actually shed light on many of the molecular mechanisms that enable evolution to create novelty by simply recombining what existed already. In this review, we will succinctly discuss the role that the recombination of protein domains has in the evolution of signaling networks, drawing from examples provided by diverse disciplines, including bioinformatics, systems and synthetic biology, and laboratory evolution.

Co-Folding of a FliF-FliG Split Domain Forms the Basis of the MS:C Ring Interface within the Bacterial Flagellar Motor

“…When FliF is bound to FliG, all three domains adopt similar conformations such that FliF:FliG aligns well with the ARM M motif and helix MC/NM in FliG M , as well as with helices 1–6 in FliG C . The striking similarity of the FliF:FliG fold with that of FliG M and FliG C suggests domain shuffling may relate all three of the FliG domains (Di Roberto et al, 2014). Either the N-terminal helix of FliG N was transferred to the C-terminus of FliF, or the FliG N :FliF C unit was fused and propagated to generate FliG M and FliG C .…”

Modular engineering of cellular signaling proteins and networks

“…These domains are often found in multi-domain proteins [6] where their combination can yield switch-like enzymes gated by upstream signals, or scaffolds that rewire and guide signaling cascades (Figure 1). In the context of evolution [7,8], development [9], differentiation [10], and disease [11,12], it is clear that new cellular behaviors often arise when existing molecular modules are recombined to generate new receptors, sensors and downstream signaling protein. In this review, we highlight recent advances in the design of synthetic signaling systems made by following the same approach.…”

“…But as described above, to engineer cellular networks we need to learn how to engineer individual signaling proteins and their connectivity. We postulate that much of the functional innovation in cellular signaling networks has evolved through repeated duplication and recombination of modular domains [7]. Researchers interested in posttranslational engineering can now use bioinformatics tools [70,71,72] to mine these naturally occurring circuits for domains that are, in essence, ‘pre-validated’ for a high degree of modularity (successfully functioning in many fusion contexts) and minimal crosstalk with other cellular components.…”

Aquerium: A web application for comparative exploration of domain‐based protein occurrences on the taxonomically clustered genome tree

“…Domains, defined as minimal structural and functional building blocks of proteins, are capable of folding autonomously and evolving independently. Single domain proteins (SDPs) were likely dominant in the early stage of life, whereas multi‐domain proteins (MDPs) are enriched with the complexity of organisms . In SDPs the domain itself functions alone while in MDPs domains work in collaboration to perform the protein function.…”