University of Oregon researcher’s evolutionary biology work attracts debate

EUGENE – University of Oregon molecular biologist Ken Prehoda is experiencing the ups and downs of becoming a viral sensation – as in social media, not an infection.

A paper on evolutionary biology he and co-authors published this month on eLifeSciences, an electronic scholarly journal, was groundbreaking enough that scientists nationally took notice – and so provocative that it became clickbait for opponents of evolutionary theory.

Prehoda and UO researcher Douglas Anderson and others made a discovery that’s giving science a new avenue for exploring how all life on Earth evolved from a single-celled entity squirming in seawater.

“How do you go from a single cell to an organized multicellular organism?” Prehoda said. “The key, really, is finding the steps.”

Prehoda’s research argues that the change from single cell to multicell was much more easily accomplished than many scientists have thought previously.

By contrast, the so-called intelligent design theory put forth by believers who say a divine entity created humans is based on the idea that organisms are so complex that they couldn’t arise from the random, step-by-step process of evolution. As a result, Prehoda now finds his email box stuffed with missives from unhappy anti-evolutionists.

The writers’ general message is: “You say we come from cells and monkeys, but we come from God,” Prehoda said.

The eLife publication sparked an explosion of interest, with write-ups in the New York Times, the Washington Post and Discovery magazine.

Readers hit the eLife link more than 30,000 times, which probably is a record for eLife, Prehoda said.

The tail

Prehoda’s team’s first problem was imagining how single-celled organisms could arrange themselves alongside their counterparts and establish a colony that could begin to cooperate and become complex, many-celled life forms.

Prehoda and other scientists realized that a single-celled organism that propelled itself with a tail (called a flagellum) would have only one way to organize. “If you want to get together in a little sphere, and you have a tail, you can’t really stick the tail any way but out,” he said. Thus oriented, when the cells divided, they had a natural structure to follow. The tail specifies how the cells divide.

In the lab, Prehoda and other paper collaborators – including some at Berkeley and Wisconsin – studied choanoflagellate, modern single-celled organisms that sometimes form colonies to pursue food.

Resurrection

Using sophisticated methods – the bread and butter of current evolutionary research – the scientists traced the organism’s genes back through the eons to the unicellular ancestor of all animal life on the planet.

They do this by computer, comparing genes – with their pairs made of A,C,G,T – and inferring the mutations that caused changes at each stage of evolution.

Finally, when they arrived at the sequence of the ancient unicellular relative of all animal life, the researchers copied the sequenced information, sent it to a laboratory in Florida, and, a few days later, a tube of clear liquid containing the DNA of an ancient molecule that hadn’t existed for hundreds of millions of years arrived.

Using a method pioneered by professor Joe Thornton at the University of Oregon – before Thornton was hired away by the University of Chicago – the researchers used the “ancestral genetic sequences” to resurrect, in the laboratory, the prehistoric protein that the unicellular organisms used to reproduce.

In experiments done on the UO campus, Prehoda, Anderson and the others determined that the protein that orients cells so they can become multicellular colonies started out as an enzyme that mutated into protein that helped drag dividing cells into place.

And, to their surprise, it took only one mutation on one gene to give single cells the ability to get into position for multicellular cooperation, Prehoda said.

The discovery opens new avenues for research, including into cancer.

Scientists can look at that confounding disease as a cell that regressed back to a more primitive unicellular state, misbehaving and ceasing to cooperate with the other cells of the body, Prehoda said. “It is a different perspective on the problem, which could make us think of different classes of genes that could be involved in cancer,” he said.

Protein wiggle

The scientist is preparing the next paper that explores how the switch from enzyme to protein occurred.

At the microscopic level, structures are all buffeted by thermal energy, causing everything to move around, Prehoda said. “What this mutation did, we think, is change how the protein wiggles. That appears to be the thing that changed the function,” he said.

All the public attention the paper drew was great, in some regards. In other ways, it was bittersweet.

When eLife published the article, the list of authors was in the wrong order, meaning the New York Times interviewed Thornton at Chicago rather than contacting Prehoda – in whose lab the bulk of the work was undertaken, Prehoda said.

Thornton tweeted that it was an oversight; he didn’t notice the order of the authors when he proofread the article before publication.

Prehoda doesn’t buy it, saying that’s not the kind of mistake a scientist makes because it’s too important. ELife since has corrected the order of authorship.

In the meantime, Prehoda said he was surprised to draw the ire of anti-evolutionists. He sticks to his findings that the evolutionary change was simple. “How could this possibly occur? It seems like it’s so complicated and requires a lot of mutations – a lot of things to happen that seem inconceivable,” he said. “Guess what? This jump happened with just one mutation.”

From a microbiology standpoint, Prehoda said, there’s no argument about evolution. “You can make evolution happen on a rapid time scale in the lab,” he said. “We’ve witnessed evolution. Evolution is just a fact, hands down.”

Future avenues

To follow all the promising leads, the UO needs to rebuild its scientific workforce. “When you look at something like biochemistry, we really only have three very active biochemists, and – look across the country – that’s ridiculously low,” Prehoda said.

The university is working to fill the job vacated by Thornton and that of biochemistry professor Andy Berglund, who recently left for the University of Florida.

In 2014, Prehoda was part of a team that proposed hiring three promising young researchers to form a “cluster of excellence” called Life at Nanoscale, but nothing so far has come of the effort. “It’s ready to go anytime. All we need is authorization for funding,” he said.

The university is in the hunt to hire three researchers for another cluster, called Genome Function, which was approved and funded by the university.

Prehoda, who directs the UO’s Institute of Molecular Biology, said he’s hopeful that the hiring will accelerate, especially since bringing on new faculty is a priority of the UO’s new president, Michael Schill.

“I get a really good vibe from President Schill,” he said. “The faculty, so far, is extremely pleased.”