Evolution of a family of molecular Rube Goldberg contraptions

Case studies of the evolution of molecular machines remain scarce.One of the most diverse and widespread homologous families of machines is the type IV filament (TFF) superfamily, comprised of type IV pili, type II secretion systems (T2SSs), archaella, and other less-wellcharacterized families.These families have functions including twitching motility, effector export, rotary propulsion, nutrient uptake, DNA uptake, and even electrical conductance, but it is unclear how such diversity evolved from a common ancestor.In this issue, Denise and colleagues take a significant step toward understanding evolution of the TFF superfamily by determining a global phylogeny and using it to infer an evolutionary pathway.Results reveal that the superfamily predates the divergence of Bacteria and Archaea, and show how duplications, acquisitions, and losses coincide with changes in function.Surprises include that tight adherence (Tad) pili were horizontally acquired from Archaea and that T2SSs were relatively recently repurposed from type IV pili.Results also enable better understanding of the function of the ATPase family that powers the superfamily.The study highlights the role of tinkering by exaptation-the repurposing of pre-existing functions for new rolesin the diversification of molecular machines.How life innovates has long fascinated humankind.Central to evolutionary innovation is exaptation, in which existing features are co-opted for new functions [1].For example, avian flight evolved by exaptation of feathers for lift (feathers originated as insulators) [2], flexible wrists for wing folding (such wrists preceded flight) [3], and hollow bones for reduced weight (air pockets evolved with other functions and did not originally enter bones) [4], leading to an integrated flight system.In turn, such exaptations push the range of subsequent innovations into the "adjacent possible" [5]-in the case of flight, feathers were further exapted to become steering devices [6].Thus, even with "nothing new under the sun," evolution repurposes or combines previously disparate elements to create new functions.Exaptation is also responsible for evolutionary innovations in the molecular machines of life.For example, injectisomes-nanoscale syringes used by Bacteria to pump toxins into our cells, causing diseases including food poisoning, chlamydia, and plague-have exapted the assembly process of bacterial flagella to secrete toxins [7,8].Another particularly rich family of inter-related molecular machines is the type IV filament (TFF) superfamily, which function as