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.
Abstract
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.
Yep. One of a handful of people who’s work I’ve been following intensely ever since I first became aware of it. I continue to be amazed that it is possible for scientists to say with considerable confidence that a particular mutation occurred in some particular gene billions of years ago, and what it’s physical and chemical, and hence phenotypic effects would have been.
Ancestral sequence reconstruction methods and the results that can be derived therefrom really deserve to be much more widely known. It is nothing short of amazing.
There are several more alpha and beta globin genes, as these exist in clusters (along with multiple pseudogenes). However, this may be beside the point you are trying to make here. What is that point?
//Whether or not this is true, it’s not relevant to the thread.//
Of course it’s relevant. Why do you talk about evolution? Human hemoglobin diversity is based on epigenetic regulation. Epigenetic modifications never result in any kind of evolution but devolution.
HBB gene: 27 disease phenotypes. Evidence for genetic decay.
HBA1 gene: 9 disease phenotypes. Evidence for genetic decay.
HBA2 gene: 7 disease phenotypes. Evidence for genetic decay.
Still only three different DNA strands used for hemoglobin protein encoding in human genome worldwide. There’s more genetic entropy than true beneficial genetic variants. Where’s the evolution?
So as we can see, the ancestor used to consist of just a single protein subunit, a monomer. This got duplicated, creating a homodimer (homo because there’s two of the same subunits connected to each other, dimer because there’s two).
The two duplicates diverged (mutations made them different from each other), resulting in a hetero(different) dimer.
Eventually they evolved to be able to assemble into a tetramer with four subunits, consisting of two heterodimers.
The proteins share an ancient common ancestor with myglobin.
That’s an example of evolution of increased molecular complexity. From a complex consisting of a single protein subunit, to one consisting of four. From a single ancestral protein coding gene, into multiple distinct protein coding genes with different functions, including the distinct functional protein coding genes of both hemoglobin and myoglobin.
Did you read the actual research article linked in the OP? It describes the evolution of the hemoglobin tetramer(consisting of four subunits, as in tetra), as in the quaternary structure of the extant hemoglobin protein complex, from an ancient precursor with only one subunit. It happened by multiple successive rounds of duplication and divergence.
Key ancestral stages in this evolutionary history are inferred by phylogenetic methods, recreated in the laboratory, and tested for how they worked and which mutations made it possible for the transition from a single subunit to four interconnected subunits to evolve.
You’re right, that was stated incorrectly. The Ancα/β ancestor is actually a pre-duplication protein that intrinsically forms homodimers. It was only after this got duplicated and the two duplicates diverged it became a heterodimer.
