Beyond DNA: How environments influence biology to make things happen

(Press-News.org) RICHLAND, Wash.—Curled up inside every single one of the trillions of cells in the human body is six feet of DNA, spooled tightly and carrying the genetic instructions that govern so much of who a person becomes. It’s a nicely wrapped package of instructions for a lifetime.

 

But having the package in hand is a far cry from understanding how it’s executed.

 

It’s been 20 years since scientists completed the Human Genome Project, sequencing the entire length of DNA found in a person. Scientists have now done the same with an amazing array of organisms, including some types of worms, mice, mosquitoes, fruit flies, trees, rice and pufferfish.

 

Science is awash in genomes and the genes within.

 

Now, scientists are exploring the world beyond genes.

 

The annual meeting of the American Association for the Advancement of Science this week in Boston will feature the session, “After the Genome: What Comes Next and Are We Ready?” The session Friday, Feb. 14 has been organized by chemist Thomas Metz and data scientist Katrina Waters of the Department of Energy’s Pacific Northwest National Laboratory. Arpana Vaniya of the University of California at Davis will serve as moderator.

 

“The genome revolution has been incredible,” said Metz, an expert on the types of small molecules that are present in living systems and that influence biological functions. “But genes don’t explain everything. In people, it’s been shown that our genes predict maybe 40 percent or less of our long-term health and disease risk. What accounts for the rest?”

 

The AAAS session brings together a panel of three experts in genomics and phenomics to explore the many emerging factors that work downstream of the DNA “instruction manual” to bring about the world around us.

 

Aristides Patrinos of New York University’s Langone Health Center will kick off the session, leading a discussion about the origins and accomplishments of the Human Genome Project as well as future directions. That project was launched by the Department of Energy and completed by a collaboration of hundreds of scientists funded through DOE and the National Institutes of Health, as well as a private sector effort headed by J. Craig Venter.

 

Gary Miller of Columbia University will explore environmental factors and how they affect biological processes to influence living organisms. Taken together, the many environmental factors that act together to influence an organism’s biology are called the “exposome.” The process happens every day in our lives. For instance, two siblings who have largely the same genes have different lifestyles; the one who is sedentary and eats poorly has a heart attack at a younger age because of those environmental influences. Beyond the discussion at AAAS, Miller is co-organizing an “Exposome Moonshot Forum” that will take place in May.

 

PNNL scientist Katrina Waters will round out the session with her talk, “Predictive Phenomics: The Next Revolution in Life Sciences.”

 

Phenomics is unknown to most people outside of science, but it’s a pivotal concept that explains much of the world around us. An organism’s phenome includes all its observable traits: tall or short, fast or slow, green eyes or blue, and so on. The genes provide a starting point for such traits, but then countless interrelated chemical changes happen moment to moment that determine what actually results. Examples include some turtles whose gender is determined by the temperature in which they incubate as eggs, and hydrangeas, whose color is determined by the pH level of soil.

 

At PNNL, Waters leads the Predictive Phenomics Initiative, where she and dozens of other researchers seek to understand not just what factors influence an organism’s biology but how they do so in concert with each other. The researchers are combining chemistry, engineering and artificial intelligence to develop microbial systems that support the future bioeconomy and enhance national security. The PNNL team has organized the first-ever Predictive Phenomics Conference, to be held April 29–May 1 in Richland, Wash. Attendees will hear from more than 100 scientists active in the discipline.

 

The Predictive Phenomics Initiative and the Exposome Moonshot both focus on understanding the extensive molecular signaling that acts downstream of DNA to influence an organism.

 

Metz points out that all DNA is made up of just four nucleotides and that just 22 amino acids make up proteins. But beyond, there are potentially millions of small chemical signaling molecules that interact with and modify DNA, RNA and proteins. Once an underestimated phenomenon, scientists today are developing tools and conducting experiments that are revealing the huge impact that these signals have on our world—whether plants grow well, people are vulnerable to illness, and yeasts are triggered to produce useful chemicals.

 

“We know a great deal about DNA and RNA,” said Metz. “We have the proper tools to comprehensively examine those molecules, and we’ve been remarkably successful at understanding them. But there is so much more to know about processes downstream of DNA and RNA, and our understanding of these is limited because we don’t have the optimal tools to answer our questions.”

 

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