Important new paper from Joe Thornton and colleagues, on the evolution of molecular complexity. Here is the accompanying News and Views piece:
Key quote from the News and Views article:
The authors’ work shows how natural selection, acting on pre-existing biophysical protein properties, can, in just a few evolutionary steps, create multimeric structures that have complex functions. Most cellular processes involve the action of protein multimers, and Pillai and colleagues’ work serves as one of the clearest examples so far of how such complexity can arise during protein evolution.
The piece also explores caveats and future directions.
Link below to the primary article itself, and abstract is below. I can help you get a PDF if you get in touch.
Most proteins associate into multimeric complexes with specific architectures1,2, which often have functional properties such as cooperative ligand binding or allosteric regulation3. No detailed knowledge is available about how any multimer and its functions arose during evolution. Here we use ancestral protein reconstruction and biophysical assays to elucidate the origins of vertebrate haemoglobin, a heterotetramer of paralogous α- and β-subunits that mediates respiratory oxygen transport and exchange by cooperatively binding oxygen with moderate affinity. We show that modern haemoglobin evolved from an ancient monomer and characterize the historical ‘missing link’ through which the modern tetramer evolved—a noncooperative homodimer with high oxygen affinity that existed before the gene duplication that generated distinct α- and β-subunits. Reintroducing just two post-duplication historical substitutions into the ancestral protein is sufficient to cause strong tetramerization by creating favourable contacts with more ancient residues on the opposing subunit. These surface substitutions markedly reduce oxygen affinity and even confer cooperativity, because an ancient linkage between the oxygen binding site and the multimerization interface was already an intrinsic feature of the protein’s structure. Our findings establish that evolution can produce new complex molecular structures and functions via simple genetic mechanisms that recruit existing biophysical features into higher-level architectures.