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(Photo: mystel/Shutterstock)

It Doesn’t Matter That Not Everything Matters

• March 14, 2014 • 12:00 PM

(Photo: mystel/Shutterstock)

Why scientists need to stop worrying about whether or not everything in biology serves a purpose.

John Brockman, the publisher and science impresario who runs the online science and culture salon Edge.org, has asked his provocative, annual Edge question: What scientific idea is ready for retirement? “Few truly new ideas are developed without abandoning old ones first,” Brockman writes. “What established scientific idea is ready to be moved aside so that science can advance?”

Here’s my candidate for forced retirement: The idea that we need to distinguish between things in biology that are there for a purpose and those that aren’t.

Because purpose is such a distinctive feature of life, discovering the functions of individual biological parts has been a major goal of life scientists for over 2,000 years. Aristotle made it a part of his scientific agenda. Galen, physician to Roman Emperor Marcus Aurelius in the second century, argued that nature had shown “forethought and art” in the design of animals’ bodies and thus the only way to fully understand an organism was to discover the purpose of each of its parts. Nearly 1,500 years later, William Harvey, who discovered the function of the heart, argued that “Nature, perfect and divine, making nothing in vain,” does not add unnecessary components to living things. Galen and Harvey ascribed biology’s exquisite functional designs to a Designer. When Charles Darwin and Alfred Wallace discovered evolution by natural selection, they got rid of the Designer but not the design.

There is no reason our DNA can’t be a mixture of the absolutely functional, the non-functional, and the sort-of functional.

Over the last century, biology has gone molecular, and the modern-day search for purpose in biology has focused on assigning functions to the cellular components that lie at the intersection of life and non-life, particularly the DNA, RNA, and protein molecules that do the major jobs of the cell. But when you get down to the nanoscale level of molecular biology, the idea that each biological part has a definite function starts to become non-functional.

The most obvious place to see this is that we have too much DNA. Only about two percent of our DNA contains the instructions necessary for making the cell’s protein components. For decades, biologists have scratched their heads over the rest. What is its function? Is most of our genome a genetic wasteland? And humans aren’t the most genetically overloaded species: Amoebas, lungfish, salamanders, and onions have a lot more DNA than we do. In an influential 1980 paper, Ford Doolittle and Carmen Sapienza argued on evolutionary grounds that our genomes likely contain DNA that was of absolutely no use to us—”whose only ‘function’ is self-preservation.” Trying to assign a biological purpose to this DNA would prove to be “ultimately futile.”

Now that the study of DNA has become more central to biological science than ever before, the issue of how to distinguish functional from non-functional DNA has become a major point of contention. Because evolution is the driving force that creates function in biology, scientists frequently identify functional genetic elements by looking for DNA that is protected by evolution from function-destroying mutational erosion. Evolutionary conservation has been a crucial standard of evidence for determining whether a segment of DNA has a purpose.

But not everyone agrees with this standard. In 2012, the ENCODE project, a consortium of scientists tasked by the National Institutes of Health to make a comprehensive catalog of all of the functional DNA elements in our genome, published their results and claimed that, contrary to what scientists believed for decades, most of our DNA does in fact have a purpose: 80 percent of our genome is functional. (Full disclosure: Some of my research is funded by ENCODE.)

ENCODE’s sensational claim was widely covered by the press as a major scientific breakthrough, but it drew harsh responses from the scientific community. The heart of the dispute was over ENCODE’s definition of function. They abandoned the evolutionary standard and relied instead on finding DNA that carried certain biochemical features that are known to occur with functional DNA. University of Houston biochemist Dan Graur and his colleagues argued that ENCODE, by defining function in this way committed the logical fallacy of affirming the consequent—it may be true that all swans are white birds, but it’s wrong to conclude that every white bird is a swan. Graur accused the ENCODE scientists of seeing swans everywhere. Just because a functional piece of DNA has a particular biochemical feature does not mean that all DNA elements with that feature are functional. The only way to avoid this problem, Graur argued, is to stick with the evolutionary standard.

On the other hand, the ENCODE results showed that, functional or not, most of our genome is biochemically active. Things happen in the cell, whether they have a purpose or not. Biologists are discovering how evolution can build complex networks of interacting genes into our genomes for no particular purpose. The functional parts of our genome are embedded in a context of purposeless genetic junk that is nevertheless not inert, and it has the potential to cause serious problems when perturbed. Evolution is ultimately a probabilistic and continuous process; new function in the genome can arise from non-functional elements, and there is no reason our DNA can’t be a mixture of the absolutely functional, the non-functional, and the sort-of functional.

Ford Doolittle, at Dalhousie University in Nova Scotia, agreed with Graur that ENCODE went too far, but he also pointed out that the argument wasn’t so much about biology as it was about words: “there is no experimentally ascertainable truth of these definitional matters other than the truth that many of the most heated arguments in biology are not about facts at all but rather about the words that we use to describe what we think the facts might be.”

Doolittle is right, and biologists, of all people, should recognize that nature doesn’t fit into the neat categories that we define. What’s true of life in general is true of molecular biology as well: Not everything happens for a purpose.

Michael White
Michael White is a systems biologist at the Department of Genetics and the Center for Genome Sciences and Systems Biology at the Washington University School of Medicine in St. Louis, where he studies how DNA encodes information for gene regulation. He co-founded the online science pub The Finch and Pea. Follow him on Twitter @genologos.

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