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Tigra Scientifica: Hooked on GKPID: Our Cells’ Molecular Carabiner

Courtesy of Wikimedia

If you’re a rock-climber, you’re familiar with the carabiner that secures your rope and prevents nasty accidents. Without the carabiner, your journey up that cliff side would be very precarious. Similarly, if our cells didn’t have a molecular carabiner, our evolutionary journey from single-cellular organisms to multicellular titans would have also been extremely dangerous. 

A 2016 article published in eLife sheds light on this molecular carabiner: guanylate kinase protein-interaction domain (GKPID). Studying this ancient protein has revealed the mechanisms behind our unicellular ancestors’ majestic evolution into multicellular critters.  

Unicellular organisms dominated Earth for billions of years. Before our single-celled ancestors could evolve to multicellular organisms, cells had to communicate with one another to cooperate in forming tissues and organ systems that comprised the multicellular creatures that first swam on Earth. 

Forming tissues was no simple task, however. Cells had to orient themselves as they divided into daughter cells. This required the use of the mitotic spindle, a complex assembly of rope-like tubes known as microtubules within the dividing cell. 

The mitotic spindle’s job is to lasso the chromosomes – along with the DNA inside – to the daughter cells. Failure of the mitotic spindle to do so results in aberrant cells and possibly fatal diseases. For the mitotic spindle to do its job, it must be properly oriented. Cue GKPID, the molecular carabiner that locks the spindle in place by hooking it to marker proteins on the cell edge.

Joseph Thornton and Kenneth Prehoda, professors from the University of Oregon, performed ancestral protein reconstruction, using gene sequencing and computer simulation to retrace GKPID’s evolutionary steps. They found that GKPID underwent “molecular exploitation” events that redesigned the protein for new functions. 

GKPID now acts as a carabiner by physically linking the spindle’s microtubules onto a molecular marker on the cell’s edge upon receiving a signal from a molecule outside the cell. The real kicker, however, is that GKPID was not originally designed to be a carabiner. Rather, this function was derived from a single mutation that drastically evolved the protein’s function. If this random but fortuitous mutation had not happened, unicellular organisms may not have evolved into multicellular creatures. 

It is truly astonishing that random chance had such a significant impact on one of science’s most marvelous events – our unicellular ancestors’ evolution into multicellular organisms.

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