Convergent evolution of the Hedgehog/Intein fold in protein splicing

The widely used molecular evolutionary clock assumes the divergent evolution of proteins. Convergent evolution has been proposed only for small protein elements but not for an entire protein fold. We investigated the structural basis of the protein splicing mechanism by class 3 inteins, which is distinct from class 1 and 2 inteins. We gathered structural and mechanistic evidence supporting the notion that the Hedgehog/INTein (HINT) superfamily fold, commonly found in protein splicing and related phenomena, could be an example of convergent evolution of an entire protein fold. We propose that the HINT fold is a structural and biochemical solution for trans-peptidyl and trans-esterification reactions.

Human germline mutation and the erratic evolutionary clock

Our understanding of the chronology of human evolution relies on the “molecular clock” provided by the steady accumulation of substitutions on an evolutionary lineage. Recent analyses of human pedigrees have called this understanding into question, by revealing unexpectedly low germline mutation rates, which imply that substitutions accrue more slowly than previously believed. Translating mutation rates estimated from pedigrees into substitution rates is not as straightforward as it may seem, however. We dissect the steps involved, emphasizing that dating evolutionary events requires not “a mutation rate,” but a precise characterization of how mutations accumulate in development, in males and females—knowledge that remains elusive.

Masers as evolutionary tracers of high-mass star formation

Determining an evolutionary clock for high-mass star formation is an important step towards realising a unified theory of star formation, as it will enable qualitative studies of the associated high-mass stars to be executed. We have carried out detailed studies of a large number of sources suspected of undergoing high-mass star formation and have found that common maser transitions offer the best opportunity to determine an evolutionary scheme for these objects. We have investigated the relative evolutionary phases of massive star formation associated with the presence or absence of combinations of water, methanol and main-line hydroxyl masers. The locations of the different maser species have been compared with the positions of 1.2 mm dust clumps, radio continuum, GLIMPSE point sources and Extended Green Objects. Comparison between the characteristics of coincident sources has revealed strong evidence for an evolutionary sequence for the different maser species in high-mass star formation regions. We present our proposed sequence for the presence of the common maser species associated with young high-mass stars and highlight recent advances. We discuss future investigations that will be made in this area by comparing data from the Methanol Multibeam (MMB) Survey with chemical clocks from the Millimetre Astronomy Legacy Team 90 GHz (MALT90) Survey.