RNA World 2.0

Most scientists believe that ribonucleic acid played a key role in the origin of life on Earth, but the versatile molecule isn’t the whole story.

© KEVIN HAND

The ubiquity and diverse functionality of ribonucleic acid (RNA) in today’s world suggest that the information polymer could well have been the leading player early on in the establishment of life on Earth, and, in theory, it’s a logical basis for primitive life. One can readily imagine that RNA, as a catalytic molecule capable of serving as a template for its own replication, might have reproduced itself and grown exponentially in the primordial environment. Perhaps such an RNA-based proto–life-form even replicated with an appropriate level of fidelity to allow natural selection to begin directing its evolution.

But there’s a snag: “The odds of suddenly having a self-replicating RNA pop out of a prebiotic soup are vanishingly low,” says evolutionary biochemist Niles Lehman of Portland State University in Oregon.

For decades, researchers from diverse fields have theorized—and argued—about how early life might have begun, and about what sparked the 3.5 billion years of evolution that led to the plethora of cell-based life that occupies almost every nook and cranny of modern Earth. Different camps emerged. So-called “metabolism first” researchers focus on understanding chemical cycles that may have materialized in a prebiotic environment and could have led to the synthesis of nucleotides and other organic molecules. Those subscribing to the theory of “genetics first” want to identify the first information molecule and understand how it arose, replicated, and evolved.

The RNA world, first posited by Francis Crick1 and others in the late 1960s, remains an attractive hypothesis. Many of the chemical hurdles that once challenged the laboratory synthesis of the molecule under presumed primordial conditions are being overcome, and in vitro evolution experiments are yielding RNA molecules that perform numerous functions, including copying themselves or other RNAs. “I don’t think there can be much doubt that RNA was a major central player as both a catalyst and an early replicator,” says Nick Lane, a biochemist at the University College London whose research falls under the “metabolism first” label. “So the RNA world is absolutely correct, as far as I’m concerned, in that.”

But the notion that RNA, on its own, spontaneously assembled and evolved on early Earth has fallen out of favor. More likely, whatever conditions spawned compounds as complex as nucleotides also generated other organics, perhaps early forms of modern amino acids and fatty acids, the constituent parts of proteins and membranes. “I’m not sure how many people anymore believe in a pure RNA world. I certainly don’t,” says Lane. “I think the field has drifted away from that, and there’s now an acknowledgment it had to be ‘dirty.’ ”

“I think most people would argue that there’s . . . more than just RNA,” agrees Matthew Powner, a “genetics first” origins-of-life researcher, also at University College London. (See “Matthew Powner: Origin Solver,” The Scientist, March 2014) “People have relaxed their opinions of the RNA world . . . from its original inception where RNA was fundamental to all parts of biology in the earliest form of life.”

Tiny mutation may have shaped modern humans, scientists say

ORIGINAL: LATimes

By Eryn Brown, Los Angeles Times

February 14, 2013

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A genetic variant could have helped people survive crippling heat by giving them extra sweat glands, says a report from a team that sought to replicate the effect in mice.

About 30,000 years ago, a tiny mutation arose in a gene known as EDAR and began to spread rapidly in central China, eventually becoming common in the region.

This week, scientists at Harvard University offered some explanations for why the EDAR mutation may have been so successful — by observing how it affects mice, animals long used in disease research but never before pressed into service for the study of human evolution.

The small change, substituting one chemical letter of DNA for another, may have helped humans in Asia survive crippling heat and humidity by endowing them with extra sweat glands, the scientists reported Thursday in the journal Cell. It may also have made people with the mutation more attractive to the opposite sex by allowing them to grow thicker hair or fuller breasts.

The research showed how scientists are getting better at zeroing in on the key DNA changes that shaped who we are today. The analysis also revealed that mutations in genes involved in bone density, skin color and immune system function were likely pivotal in helping humans adapt to new environments as they spread throughout the world.

"You can let the genome tell you what's been important in human evolution," said Harvard computational geneticist Pardis Sabeti, senior author of the two studies published in Cell.

Living beings evolve through a process known as selection. Organisms with advantageous traits thrive, passing their DNA to another generation. Harmful traits die off when their hosts can't live long enough to reproduce.

Scientists can recognize patterns in DNA that indicate a particular version of a gene has spread through a population because it boosts survival. But those beneficial mutations are usually passed down along with thousands of other variants that happen to live in their chromosomal neighborhood.

That has made it hard for researchers to determine exactly which genetic tweaks conferred the competitive advantage.

"It's like you walk around a ghost town and you see the clues that something happened, but you don't know exactly what or how," said UC Santa Cruz biomolecular engineer Ed Green, who was not involved in the new studies.

Sabeti and an international group of colleagues are using multiple techniques to dig out the key drivers of human evolution in the avalanche of genetic data made possible by faster, cheaper sequencing technology. A single human genome contains 3 billion pairs of the chemical letters A, C, G and T.

To sort through all that, the researchers used powerful computers to identify genetic changes that seemed to be linked to evolutionary change. They examined the DNA of 179 people from Utah, East Asia and West Africa and revealed hundreds of potentially key variants, including mutations that made bones stronger and helped people absorb more vitamin D from the sun as they moved to northern latitudes.

Sabeti wanted to understand more about how these mutations influenced human traits. Such work requires experimentation — and that is where the mice entered the picture.

The EDAR gene was already known to influence hair thickness and to alter tooth shape in humans. But Sabeti wasn't sure whether the mutation her team turned up was a key change that drove human evolution.

To arrive at an answer, she and her collaborators genetically engineered mice that had the Asian version of EDAR.

They found that, as with humans, the mice had thicker hair than their counterparts without the variant. They also displayed traits the researchers hadn't expected to see, including more sweat glands and changes in their mammary glands. (The variant had no discernible effect on the animals' teeth.)

Next, the team examined the fingertips and EDAR genes of 623 people in Taizhou, China, to see if those who had the mutation also had a larger number of active sweat glands. They did.

The results present a fuller picture of how the EDAR mutation may have helped drive evolution.

People who inherited the variant may have reproduced more successfully because having more sweat glands helped their bodies cool off in hot, humid weather.

Or it might have spread through sexual selection. Thicker hair may have been more appealing in a mate. In addition, the mutation could have changed breast size or shape, making people who had it more attractive to the opposite sex.

That scientists could study a mouse and reveal such insights into human evolution was "amazing," said Green, who co-wrote an essay about the work that was also published in Cell on Thursday.

The story was similar for the TLR-5 gene, which is involved in protecting the body from certain bacteria. Instead of testing in mice, the scientists used cell cultures in lab dishes to demonstrate that the mutation reduced the immune system's inflammatory response to a key protein in the bacterial pathogens.

The team's analysis suggested that many of the key genetic changes weren't in genes themselves, but in regions of the chromosome that scientists think contain instructions for how those genes should be turned on and off, or tuned up or down, Sabeti said.

The work offers a long-awaited view into the key mutations that billions of us share and that made us who we are, said David Kingsley, an evolutionary geneticist at Stanford University who was not involved in the new studies.

"We're reading a book of information about our past that has never been available before," he said.

eryn.brown@latimes.com

Bioinspired Fibers Change Color when Stretched

ORIGINAL: Wyss Institute

January 28, 2013

The so-called "bastard hogberry," shown here floating in water (which changes its apparent color), has inspired a new type of photonic fiber. (Image courtesy of Peter Vukusic.)

Color-tunable photonic fibers mimic the fruit of the "bastard hogberry" plant

A team of materials scientists at Harvard University and the University of Exeter, UK, have invented a new fiber that changes color when stretched. Inspired by nature, the researchers identified and replicated the unique structural elements that create the bright iridescent blue color of a tropical plant's fruit.

The multilayered fiber, described today in the journal Advanced Materials, could lend itself to the creation of smart fabrics that visibly react to heat or pressure.

"Our new fiber is based on a structure we found in nature, and through clever engineering we've taken its capabilities a step further," says lead author Mathias Kolle, a postdoctoral fellow at the Harvard School of Engineering and Applied Sciences (SEAS). "The plant, of course, cannot change color. By combining its structure with an elastic material, however, we've created an artificial version that passes through a full rainbow of colors as it's stretched."

The photonic fibers are made by wrapping multiple layers of polymer around a glass core, which is later etched away. The thickness of the layers determines the apparent color of the fiber, which can range across the entire visible spectrum of light. (Image courtesy of Mathias Kolle.)

Since the evolution of the first eye on Earth more than 500 million years ago, the success of many organisms has relied upon the way they interact with light and color, making them useful models for the creation of new materials. For seeds and fruit in particular, bright color is thought to have evolved to attract the agents of seed dispersal, especially birds.

The fruit of the South American tropical plant, Margaritaria nobilis, commonly called "bastard hogberry," is an intriguing example of this adaptation. The ultra-bright blue fruit, which is low in nutritious content, mimics a more fleshy and nutritious competitor. Deceived birds eat the fruit and ultimately release its seeds over a wide geographic area.

Zooming in on the structure of the hogberry fruit, multiple scales of repeating architecture become clear. (Image courtesy of Mathias Kolle.)

"The fruit of this bastard hogberry plant was scientifically delightful to pick," says principal investigator Peter Vukusic, Associate Professor in Natural Photonics at the University of Exeter. "The light-manipulating architecture its surface layer presents, which has evolved to serve a specific biological function, has inspired an extremely useful and interesting technological design."

Vukusic and his collaborators at Harvard studied the structural origin of the seed's vibrant color. They discovered that the upper cells in the seed's skin contain a curved, repeating pattern, which creates color through the interference of light waves. (A similar mechanism is responsible for the bright colors of soap bubbles.) The team's analysis revealed that multiple layers of cells in the seed coat are each made up of a cylindrically layered architecture with high regularity on the nano- scale.

The researchers at Harvard developed a unique method of producing the photonic fibers; they believe it can be scaled up for industrial fabrication. (Image courtesy of Mathias Kolle.)

The team replicated the key structural elements of the fruit to create flexible, stretchable and color-changing photonic fibers using an innovative roll-up mechanism perfected in the Harvard laboratories.

"For our artificial structure, we cut down the complexity of the fruit to just its key elements," explains Kolle. "We use very thin fibers and wrap a polymer bilayer around them. That gives us the refractive index contrast, the right number of layers, and the curved, cylindrical cross-section that we need to produce these vivid colors."

The researchers say that the process could be scaled up and developed to suit industrial production.

"Our fiber-rolling technique allows the use of a wide range of materials, especially elastic ones, with the color-tuning range exceeding by an order of magnitude anything that has been reported for thermally drawn fibers," says coauthor Joanna Aizenberg, Amy Smith Berylson Professor of Materials Science at Harvard SEAS, and Kolle's adviser. Aizenberg is also Director of the Kavli Institute for Bionano Science and Technology at Harvard and a Core Faculty Member at the Wyss Institute for Biologically Inspired Engineering at Harvard.

The fibers' superior mechanical properties, combined with their demonstrated color brilliance and tunability, make them very versatile. For instance, the fibers can be wound to coat complex shapes. Because the fibers change color under strain, the technology could lend itself to smart sports textiles that change color in areas of muscle tension, or that sense when an object is placed under strain as a result of heat.

Additional coauthors included Alfred Lethbridge at the University of Exeter, Moritz Kreysing at Ludwig Maximilians University (Germany), and Jeremy B. Baumberg, Professor of Nanophotonics at the University of Cambridge (UK).

This research was supported by the U.S. Air Force Office of Scientific Research Multidisciplinary University Research Initiative, by the UK Engineering and Physical Sciences Research Council, and through a postdoctoral research fellowship from the Alexander von Humboldt Foundation. The researchers also benefited from facilities at the Harvard Center for Nanoscale Systems, which is part of the National Nanotechnology Infrastructure Network supported by the U.S. National Science Foundation. The Wyss Institute for Biologically Inspired Engineering at Harvard also contributed to this research.

CONTACT: Caroline Perry, (617) 496-1351