Evolution of an ancient protein function involved in organized multicellularity in animals

Abstract

To form and maintain organized tissues, multicellular organisms orient their mitotic spindles relative to neighboring cells. A molecular complex scaffolded by the GK protein-interaction domain (GKPID) mediates spindle orientation in diverse animal taxa by linking microtubule motor proteins to a marker protein on the cell cortex localized by external cues. Here we illuminate how this complex evolved and commandeered control of spindle orientation from a more ancient mechanism. The complex was assembled through a series of molecular exploitation events, one of which – the evolution of GKPID’s capacity to bind the cortical marker protein – can be recapitulated by reintroducing a single historical substitution into the reconstructed ancestral GKPID. This change revealed and repurposed an ancient molecular surface that previously had a radically different function. We show how the physical simplicity of this binding interface enabled the evolution of a new protein function now essential to the biological complexity of many animals.DOI: http://dx.doi.org/10.7554/eLife.10147.001

A Relay Pathway between Arginine and Tryptophan Metabolism Confers Immunosuppressive Properties on Dendritic Cells

“…In conclusion, our data, besides further underlining the importance of critical pathways linking metabolism and immunity in multicellular animals, suggest that the appearance of a highly evolved form of biologic response such as immune regulation would rely on a network based on the co-option of two ancient pathways, i.e., Arg and Trp catabolisms (Anderson et al., 2016) as reinforced by TGF-β. A consequence of this could be that tumors, considered to be the result of an evolutionary process (Billaud and Santoro, 2011), have become particularly apt to co-opt metabolic and immunosuppressive networks to propel their generation and progression.…”

Choanoflagellate models — Monosiga brevicollis and Salpingoeca rosetta

“…rosetta has also emerged as model to reconstruct the ancestral functions of synaptic proteins like Homer, PSD-95 and CamKII [13 , 44,45]. The postsynaptic density protein Homer, which controls abundance and orientation of membrane receptors and regulates calcium signaling in neurons [46], unexpectedly localizes to the nucleus in S. rosetta (Figure 2j) [13 ].…”

Evolution of protein specificity: insights from ancestral protein reconstruction

“…Several recent studies, however, have documented protein families in which the specific biological functions of present-day proteins evolved de novo from ancestral proteins that lacked those functions, and they reveal the mechanisms by which those new functions evolved [39–43]. Here we survey these findings, discussing three case studies in which different kinds of biological specificity evolved de novo : substrate-specificity of an enzyme, ligand-specificity of an allosterically regulated protein, and DNA-specificity of a transcription factor.…”