Using what they call “molecular time travel,” researchers from the University of Oregon, the University of Chicago Medical Center, and elsewhere have found that multicellular life formed largely as the result of a single, random mutation more than 600 million years ago.
Writing in the latest edition of the journal eLife, the study authors explained that experiments conducted using “resurrected” ancient proteins revealed the mechanisms through which single-celled ancestral organisms transitioned into animals capable of forming organized tissue.
“Our experiments show how biological complexity can evolve through simple, high-probability genetic paths,” co-senior author Dr. Joe Thornton, professor of human genetics and ecology and evolution at the University of Chicago, said in a statement. “Before the last common ancestor of all animals, when only single-celled organisms existed on Earth, just one tiny change in DNA sequence caused a protein to switch from its primordial role as an enzyme to a new function that became essential to organize multicellular structures.”
The research, which also involved experts form the Medical College of Wisconsin and Howard Hughes Medical Institute at the University of California, Berkeley, is said to be the first to detail molecular mechanisms involved in the evolution of multicellular organisms. The findings could also solve the mysteries of evolution and shed new light on diseases such as cancer.
Mechanisms of cell orientation play a key role
Dr. Thornton and his colleagues focused on mitotic spindle orientation, which uses a structure in an organism’s cells that governs the direction in which those cells divide relative to other, nearby cells—an essential part of maintaining organized tissues. This structure, the mitotic spindle, is a network of protein filaments that separates chromosomes prior to division.
In most types of creatures, a protein scaffold known as the guanylate kinase protein interaction domain (GK-PID) rotates the spindle relative to the cells around it by binding to a pair of partner molecules: an “anchor” protein on the inside of the cell membrane which indicates the positions of nearby cells, and a motor protein that pulls on mitotic spindle filaments.
After they are linked by GK-PID, the motors pull chromosomes towards the anchors, ensuring that new daughter cells are oriented correctly. To study how this function originally evolved in multicellular creatures, Dr. Thornton and his colleagues used a technique called ancestral protein reconstruction to reverse-engineer the evolution of different genes and proteins.
Using gene sequencing and computational methods, the researchers were able to see molecular changes and infer how proteins behaved in the ancient past. They sequenced the genomes of more than 40 types of organisms and found that the anchor protein first appeared in the lineage leading to complex animal development, essentially replacing another molecule which served a similar purpose in GK-PID and setting the groundwork for the formation of tissues.
While the findings provide the first in-depth explanation of how this function first evolved in complex multicellular lifeforms, Dr. Thornton emphasized that there are still many other parts of the evolution of spindle orientation that remain poorly understood, as well as the possibility that other functions could have helped in the transition away from single-celled organisms.
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Feature Image: Wakayama et al., PLoS 2009
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