Where there's smoke and a mutation there may be an evolutionary edge for humans

A genetic mutation may have helped modern humans adapt to smoke exposure from fires and perhaps sparked an evolutionary advantage over their archaic competitors, including Neanderthals, according to a team of researchers.

A genetic mutation that is now ubiquitous in humans may have increased our tolerance to smoke, leading to an 
evolutionary advantage over other hominins, such as Neanderthals [Credit:Web]

Modern humans are the only primates that carry this genetic mutation that potentially increased tolerance to toxic materials produced by fires for cooking, protection and heating, said Gary Perdew, the John T. and Paige S. Smith Professor in Agricultural Sciences, Penn State. At high concentrations, smoke-derived toxins can increase the risk of respiratory infections. For expectant mothers, exposure to these toxins can increase the chance of low birth weight and infant mortality.

The mutation may have offered ancient humans a sweet spot in effectively processing some of these toxins -- such as dioxins and polycyclic aromatic hydrocarbons -- compared to other hominins.

"If you're breathing in smoke, you want to metabolize these hydrophobic compounds and get rid of them, however, you don't want to metabolize them so rapidly that it overloads your system and causes overt cellular toxicity," said Perdew.

The researchers, who released their findings in the current issue of Molecular Biology and Evolution, suggest that a difference in the aryl hydrocarbon receptor -- which regulates the body's response to polycyclic aromatic hydrocarbons -- between humans, Neanderthals and other non-human primates may have made humans more desensitized to certain smoke toxins. The mutation in the receptor is located in the middle of the ligand-binding domain and is found in all present-day humans, Perdew added.

Ligands are small molecules that attach to receptor proteins in certain areas in much the same way that keys fit into locks.

Troy Hubbard, Ph.D candidate in molecular biology, left, reviews as chart of proteins collected from a sample 
with Dr. Gary Perdew in their Life Sciences Lab at Penn State [Credit: Patrick Mansell]

"For Neanderthals, inhaling smoke and eating charcoal-broiled meat, they would be exposed to multiple sources of polycyclic aromatic hydrocarbons, which are known to be carcinogens and lead to cell death at high concentrations," said Perdew. "The evolutionary hypothesis is, if Neanderthals were exposed to large amounts of these smoke-derived toxins, it could lead to respiratory problems, decreased reproductive capacity for women and increased susceptibility to respiratory viruses among preadolescents, while humans would exhibit decreased toxicity because they are more slowly metabolizing these compounds."

There is evidence that both humans and Neanderthals used fire, according to George Perry, assistant professor of anthropology and biology, Penn State, who worked with Perdew.

"Our hominin ancestors -- they would technically not be called humans at that time -- were likely using fire at least a million years ago, and some infer an earlier control and use of fire approximately 2 million years ago," said Perry.

Fire would have played an important role for both humans and Neanderthals.

"Cooking with fire could have allowed our ancestors to incorporate a broader range of foods in our diets, for example, by softening roots and tubers that might otherwise have been hard to chew," Perry said. "Cooking could also help increase the digestibility of other foods, both in chewing time and reduced energetic investment in digestion."

Adding cell culture media to cells in Gary Perdew's Life Sciences Laboratory 
[Credit: Patrick Mansell]

Fire also provided warmth, particularly in the higher latitudes, according to Perry.

"Besides heating and cooking, humans used -- and still use -- fire for landscape burning and as part of hunting and gathering, and now as part of agriculture," said Perry.

The study may also lend support to a recent theory that the invention of cooking may have helped humans thrive, according to Perdew.

He also suggested that the receptor might give humans a better tolerance for cigarette smoke, allowing people to smoke, but also putting them at risk of cancer and other chronic diseases.

"Our tolerance has allowed us to pick up bad habits," Perdew said.

The researchers used computational and molecular techniques to examine the difference in the genetics of polycyclic aromatic hydrocarbon tolerance between humans and Neanderthals. They examined a genomic database of humans, Neanderthals and a Denisovan, a hominin more closely related to Neanderthals than humans.

"We thought the differences in aryl hydrocarbon receptor ligand sensitivity would be about ten-fold, but when we looked at it closely, the differences turned out to be huge," said Perdew. "Having this mutation made a dramatic difference. It was a hundred-fold to as much of a thousand-fold difference."

In contrast, the sensitivity of the aryl hydrocarbon receptor for some endogenous -- produced in the body -- ligands is the same between human and Neanderthal, which further illustrates that modern humans may have adapted to specific environmental toxin exposures through this critical mutation in the aryl hydrocarbon receptor.

Author: Matt Swayne| Source: Penn State University [August 02, 2016]

Where there's smoke and a mutation there may be an evolutionary edge for humans

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'Red gene' in birds and turtles suggests dinosaurs had bird-like colour vision

Earlier this year, scientists used zebra finches to pinpoint the gene that enables birds to produce and display the colour red.

Dinosaurs would have had the same ability to see a wide spectrum of redness as birds and turtles, 
according to a new study [Credit: Web]

Now, a new study shows the same 'red gene' is also found in turtles, which share an ancient common ancestor with birds. Both share a common ancestor with dinosaurs.

The gene, called CYP2J19, allows birds and turtles to convert the yellow pigments in their diets into red, which they then use to heighten colour vision in the red spectrum through droplets of red oil in their retinas.

Birds and turtles are the only existing tetrapods, or land vertebrates, to have these red retinal oil droplets. In some birds and a few turtle species, red pigment produced by the gene is also used for external display: red beaks and feathers, or the red neck patches and rims of shells seen in species such as the painted turtle.

The scientists mined the genetic data of various bird and reptile species to reconstruct an evolutionary history of the CYP2J19 gene, and found that it dated back hundreds of millions of years in the ancient archelosaur genetic line - the ancestral lineage of turtles, birds and dinosaurs.

The findings, published today in the journal Proceedings of the Royal Society B, provide evidence that the 'red gene' originated around 250 million years ago, predating the split of the turtle lineage from the archosaur line, and runs right the way through turtle and bird evolution.

Scientists say that, as dinosaurs split from this lineage after turtles, and were closely related to birds, this strongly suggests that they would have carried the CYP2J19 gene, and had the enhanced 'red vision' from the red retinal oil.

This may have even resulted in some dinosaurs producing bright red pigment for display purposes as well as colour vision, as seen in some birds and turtles today, although researchers say this is more speculative.

The painted turtle, widespread across North America, is one of the turtle species that uses red pigment for external display 
as well as colour vision. Samples from this species were used in the new study [Credit: Nicole Valenzuela]

"These findings are evidence that the red gene originated in the archelosaur lineage to produce red for colour vision, and was much later independently deployed in both birds and turtles to be displayed in the red feathers and shells of some species, going from seeing red to being red," says senior author Dr Nick Mundy, from the University of Cambridge's Department of Zoology.

"This external redness was often sexually selected as an 'honest signal' of genuine high quality in a mate," he says.

The previous research in zebra finches showed a possible link between red beaks and the ability to break down toxins in the body, suggesting external redness signals physiological quality, and there is some evidence that colouration in red-eared terrapins is also linked to honest signalling.

"The excellent red spectrum vision provided by the CYP2J19 gene would help female birds and turtles pick the brightest red males," says Hanlu Twyman, the PhD student who is lead author on the work.

The structure of retinas in the eye includes cone-shaped photoreceptor cells. Unlike mammals, avian and turtle retinal cones contain a range of brightly-coloured oil droplets, including green, yellow and red.

These oil droplets function in a similar way to filters on a camera lens. "By filtering the incoming light, the oil droplets lead to greater separation of the range of wavelengths that each cone responds to, creating much better colour sensitivity," explains Mundy.

"Humans can distinguish between some shades of red such as scarlet and crimson. However, birds and turtles can see a host of intermediate reds between these two shades, for example. Our work suggests that dinosaurs would have also had this ability to see a wide spectrum of redness," he says.

Over hundreds of millennia of evolution, the CYP2J19 gene was independently deployed to generate the red pigments in the external displays of some bird species and a few turtle species. The scientists say their data indicate that co-option of CYP2J19 for red colouration in dinosaurs would also have been possible.

The ancestral lineage that led to scaly lizards and snakes split from the archosaur line before turtles, and, as the findings suggest, before the origin of the red gene. These reptiles either lack retinal oil droplets, or have yellow and green but not red.

However, the crocodilian lineage split from the archelosaur line after turtles, yet crocodiles appear to have lost the CYP2J19 gene, and have no oil droplets of any colour in their retinal cones.

Mundy says there is some evidence that oil droplets were lost from the retinas of species that were nocturnal for long periods of their genetic past, and that this hypothesis fits for mammals and snakes, and may also be the case with crocodiles.

Source: University of Cambridge [August 02, 2016]

'Red gene' in birds and turtles suggests dinosaurs had bird-like colour vision

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DNA's dynamic nature makes it well-suited to serve as the blueprint of life

A new study could explain why DNA and not RNA, its older chemical cousin, is the main repository of genetic information. The DNA double helix is a more forgiving molecule that can contort itself into different shapes to absorb chemical damage to the basic building blocks�A, G, C and T�of genetic code. In contrast, when RNA is in the form of a double helix it is so rigid and unyielding that rather than accommodating damaged bases, it falls apart completely.

The DNA double helix (shown on the left) can contort itself into different shapes to absorb chemical damage
 to the basic building blocks (A, G, C and T, depicted by a black dot) of genetic code. In contrast, an RNA 
double helix (shown on the right) is so rigid and unyielding that rather than accommodating 
damaged bases, it falls apart completely [Credit: Huiqing Zhou, Duke University]

The research, published August 1, 2016 in the journal Nature Structural and Molecular Biology, underscores the dynamic nature of the DNA double helix, which is central to maintaining the stability of the genome and warding off ailments like cancer and aging. The finding will likely rewrite textbook coverage of the difference between the two purveyors of genetic information, DNA and RNA.

"There is an amazing complexity built into these simple beautiful structures, whole new layers or dimensions that we have been blinded to because we didn't have the tools to see them, until now," said Hashim M. Al-Hashimi, Ph.D., senior author of the study and professor of biochemistry at Duke University School of Medicine.

DNA's famous double helix is often depicted as a spiral staircase, with two long strands twisted around each other and steps composed of four chemical building blocks called bases. Each of these bases contain rings of carbon, along with various configurations of nitrogen, oxygen, and hydrogen. The arrangement of these atoms allow G to pair with C and A to pair with T, like interlocking gears in an elegant machine.

When Watson and Crick published their model of the DNA double helix in 1953, they predicted exactly how these pairs would fit together. Yet other researchers struggled to provide evidence of these so-called Watson-Crick base pairs. Then in 1959, a biochemist named Karst Hoogsteen took a picture of an A-T base pair that had a slightly skewed geometry, with one base rotated 180 degrees relative to the other. Since then, both Watson-Crick and Hoogsteen base pairs have been observed in still images of DNA.

Five years ago, Al-Hashimi and his team showed that base pairs constantly morph back and forth between Watson-Crick and the Hoogsteen configurations in the DNA double helix. Al-Hashimi says that Hoogsteen base pairs typically show up when DNA is bound up by a protein or damaged by chemical insults. The DNA goes back to its more straightforward pairing when it is released from the protein or has repaired the damage to its bases.

"DNA seems to use these Hoogsteen base pairs to add another dimension to its structure, morphing into different shapes to achieve added functionality inside the cell," said Al-Hashimi.

Al-Hashimi and his team wanted to know if the same phenomenon might also be occurring when RNA, the middleman between DNA and proteins, formed a double helix. Because these shifts in base pairing involve the movement of molecules at an atomic level, they are difficult to detect by conventional methods. Therefore, Al-Hashimi's graduate student Huiqing Zhou used a sophisticated imaging technique known as NMR relaxation dispersion to visualize these tiny changes. First, she designed two model double helices�one made of DNA and one made of RNA. Then, she used the NMR technique to track the flipping of individual G and A bases that make up the spiraling steps, pairing up according to Watson-Crick or Hoogsteen rules.

Prior studies indicated that at any given time, one percent of the bases in the DNA double helix were morphing into Hoogsteen base pairs. But when Zhou looked at the corresponding RNA double helix, she found absolutely no detectable movement; the base pairs were all frozen in place, stuck in the Watson-Crick configuration.

The researchers wondered if their model of RNA was an unusual exception or anomaly, so they designed a wide range of RNA molecules and tested them under a wide variety of conditions, but still none appeared to contort into the Hoogsteen configuration. They were concerned that the RNA might actually be forming Hoogsteen base pairs, but that they were happening so quickly that they weren't able to catch them in the act. Zhou added a chemical known as a methyl group to a specific spot on the bases to block Watson-Crick base pairing, so the RNA would be trapped in the Hoogsteen configuration. She was surprised to find that rather than connecting through Hoogsteen base pairs, the two strands of RNA came apart near the damage site.

"In DNA this modification is a form of damage, and it can readily be absorbed by flipping the base and forming a Hoogsteen base pair. In contrast, the same modification severely disrupts the double helical structure of RNA," said Zhou, who is lead author of the study.

The team believes that RNA doesn't form Hoogsteen base pairs because its double helical structure (known as A-form) is more compressed than DNA's (B-form) structure. As a result, RNA can't flip one base without hitting another, or without moving around atoms, which would tear apart the helix.

"For something as fundamental as the double helix, it is amazing that we are discovering these basic properties so late in the game," said Al-Hashimi. "We need to continue to zoom in to obtain a deeper understanding regarding these basic molecules of life."

Source: Duke University [August 01, 2016]

DNA's dynamic nature makes it well-suited to serve as the blueprint of life

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