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A new study led by scientists at The Scripps Research Institute (TSRI) offers a intertwine on a popular theory for how life on Earth began about four billion years ago, challenging the "RNA world" hypothesis, a theory for how RNA molecules evolved to create proteins and DNA. Instead, the new research offers evidence for a world where RNA and DNA evolved simultaneously.

"Even if you believe in a RNA-only world, you have to believe in something that existed with RNA to help it move forward," said Ramanarayanan Krishnamurthy, associate professor of chemistry at TSRI and senior author of the new study. "Why not think of RNA and DNA rising together, rather than trying to convert RNA to DNA by means of some fantastic chemistry at a prebiotic stage?"

Researchers have explored the RNA world hypothesis for more than 30 years. The idea behind this theory is that a series of chemical reactions led to the formation of self-replicating RNA molecules. RNA then evolved to create proteins and enzymes that resembled early versions of what makes up life today. Eventually, these enzymes helped RNA produce DNA, which led to complex organisms.

On the surface, RNA and DNA molecules look similar, with DNA forming a ladder-like structure (with nucleobase pairs as the rungs and sugar molecule backbones as the sides) and RNA forming what looks like just one side of a ladder.

If the RNA world theory is accurate, some researchers believe there would have been many cases where RNA nucleotides were mixed with DNA backbones, creating "heterogeneous" strands. If stable, these blended "chimeras" would have been an intermediate step in the transition to DNA.

However, the new study shows a important loss of stability when RNA and DNA share the same backbone. The chimeras do not stay together as well as pure RNA or pure DNA, which would adjust their ability to grasp genetic information and replicate.

"We were surprised to see a very deep drop in what we would call the thermal stability," said Krishnamurthy, who in addition to his position at TSRI has joint appointments with the National Science Foundation (NSF)-National Aeronautics and Space Administration (NASA) Center for Chemical Evolution and the Simons Collaboration on the Origins of Life. This instability appeared to be due to a difference in the DNA sugar molecule structure versus the RNA sugar molecule.

The finding supported previous research from Nobel laureate and Harvard University Chemistry and Chemical Biology Professor Jack Szostak that showed a loss of stability.

Because of this instability, chimeras in the RNA world would have likely died off in favor of more stable RNA molecules. This reflects what scientists see in cells today: If RNA nucleobases mistakenly join a DNA strand, sophisticated enzymes will rush to fix the mistake. Evolution has led to a system that favors more stable, "homogeneous" molecules.

These sophisticated enzymes were probably not around at the time of RNA and DNAs early evolution, so these substitutions may have had a crippling effect on the molecules ability to replicate and function. "The transition from RNA to DNA would not have been easy without mechanisms to grasp them separate," said Krishnamurthy.

This realization led the scientists to consider an alternate theory: RNA and DNA may have arisen in tandem.
Krishnamurthy emphasized that his lab is not the first to propose this theory, but the findings on chimeric instability give scientists new evidence to consider. If the two evolved at the same time, DNA could have established its own homogeneous system early on. RNA could have still evolved to produce DNA, but that may have occurred after it first met DNA and got to know its raw materials.

Krishnamurthy added that scientists will never know exactly how life began (barring the invention of a time machine), but by considering circumstances of early evolution, scientists can gain insights into the fundamentals of biology.

The Daily Galaxy via The Scripps Research Institute

Image credit: Human Sculpture in Swiss Alps by  Antony Gormley 

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Researchers at the National Institute of Mental Health (NIMH) have produced the first direct evidence that parts of our brains implicated in mental disorders may be shaped by a "residual echo" from our ancient past. The more a persons genome carries genetic vestiges of Neanderthals, the more certain parts of his or her brain and skull resemble those of humans evolutionary cousins that went extinct 40,000 years ago, says NIMHs Karen Berman, M.D. NIMH is part of the National Institutes of Health.

In exacting, the parts of our brains that enable us to use tools and visualize and locate objects owe some of their lineage to Neanderthal-derived gene variants that are part of our genomes and affect the shape of those structures -- to the extent that an individual harbors the ancient variants. But this may involve trade-offs with our social brain. The evidence from MRI scans suggests that such Neanderthal-derived genetic variation may affect the way our brains labor today -- and may detain clues to understanding deficits seen in schizophrenia and autism-related disorders, say the researchers.

Dr. Berman, Michael Gregory, M.D., of the NIMH Section on Integrative Neuroimaging, and colleagues, report on their magnetic resonance imaging (MRI) study published online, July 24, 2017 in the journal Scientific Reports.

The image above  of MRI data shows areas of the skull preferentially affected by the amount of Neanderthal-derived DNA.

During their primordial migration out of Africa, ancestors of present-day humans are thought to have interbred with Neanderthals, whose brain characteristics can be inferred from their fossilized skulls. For example, these indicate that Neanderthals had more prominent visual systems than modern humans.

Might some of us, more than others, harbor Neanderthal-derived gene variants that may predisposition our brains toward trading sociability for visuospatial prowess -- or vice versa? The new study adds support to this possibility by showing how these gene variants influence the structure of brain regions underlying those abilities.

To test this possibility, Gregory and Berman measured the impact of Neanderthal variants on MRI measures of brain structure in a sample of 221 participants of European ancestry, drawn from the NIMH Genetic Study of Schizophrenia.

The new MRI evidence points to a a gene variant shared by modern-day humans and Neanderthals that is likely involved in development of the brains visual system. Similarly, Neanderthal variants impacting development of a exacting suspect brain area may help to inform cognitive disability seen in certain brain disorders, say the researchers.

For example, in 2012, Berman and colleagues reported on how genetic variation shapes the structure and function of a brain area called the Insula in the autism-related disorder Williams Syndrome. People with this rare genetic disorder are overly sociable and visuo-spatially impaired - conspicuously opposite to the hypothesized Neanderthal propensities and more typical cases on the autism spectrum. Mice in which a gene affected by Williams syndrome is experimentally deleted show increased separation anxiety. And just last week, researchers showed that the same genetic variability also appears to explain why dogs are friendlier than wolves.

The Daily Galaxy via NIMH

Image credit: With thanks to Peter the Great Museum