Your Lifestyle as a Child may Influence you DNA for Life

Noted geneticist Snoop Dogg once said--and I’m paraphrasing here--that no matter where one goes in life, one’s surroundings during one's formative years stay with one for life. No matter where you go, you can’t change where you’re from (I think Prof. Dogg was actually calling back to an old Comrads lyric from the song Homeboyz--I’m sure you all will correct me in the comments). Findings published today in the International Journal of Epidemiology suggest that he may have been correct--socio-economic status and living standards early in life may actually cause changes to your DNA that you carry with you for life, regardless of how your living conditions change along the way.

In some ways, we already knew that. Some adult diseases--type 2 diabetes, coronary heart disease, etc.--have been linked to socio-economic disadvantages in early life. But we don’t really know why or how. Researchers in Canada and the UK may have just found the key.

 Their sample size is admittedly small, but what they found was significant. In 40 research patients in the UK that are participating in an ongoing study that has documented many aspects of their lives, researchers looked at differences in gene methylation. Methylation is an epigenetic modification to one’s DNA that changes a gene’s activity, generally reducing that activity within the genome. Various factors can influence methylation, including environmental conditions.

In their sample, the researchers looked at DNA taken from the subjects at age 45. They chose subjects that had come from either very high or very low standards of living, and they looked at differences in DNA methylation across some 20,000 genes. They found that 1,252 methylation differences were associated with socio-economic circumstances in early life while just 545 were associated with socio-economic circumstances in adulthood, suggesting that where you come from really does make an impact on the very fiber of your biological being.

Moreover, the methylation patterns were clustered together in large swaths of DNA, suggesting an epigenetic pattern linked to humans’ early environments. That’s actually good news. If we know some diseases are linked to a person’t early upbringing, and we can see where there are changes happening in the DNA during early life, then we can narrow the window on where in the genome things like coronary heart disease and diabetes take root. Future research could peg where certain methylation differences are associated with specific diseases, then target those areas with drugs or other treatments.

by "environment clean generations"

You Could Probably Live For 1000 Years

According to Richard Seymour, founder of design agency Seymourpowell: "The future's a secret". And if he told us anything that he has learnt from the companies he has worked with, he would have to kill us.

"The future's here, it's just packed away in places where the majority can't see it." How many of us in the audience, for example, know Apple's plans for the next seven years? Companies are pathologically guarding their plans, and Seymour is one of the people who gets to see what they think the future will hold.

 Siri (Apple's new voice-controlled software in iOS 5) is one of the developments that he lauds but adds that if such "proxies" are going to rise, they need to be with their "owner". "I want it with me, not in the cloud. It doesn't live behind the glass, it lives with me," he says.

But, it is genome sequencing that is set to have the biggest impact on design in the coming decades, says Seymour. Pulling from his pocket a slide containing "an entire human" (pictured), he explained how this one slide has gone from costing thousands to hundreds of pounds; and could, in the next couple of years, "be available on the back of a cereal packet". Already, he said, we have DNA-based cosmeceuticals, and the subsequent scrum to buy these products is evidence of their potential.

We may also need their powers if we continue to live longer and longer. "The first person to live for a thousand years is possibly already alive", says Seymour. And, of those of us sitting at Wired 2011 aged between 20-30, there "will certainly" be some who reach 130 years old. This, he says, "will have an instantaneous and catastrophic effect on the world population".

To solve the space problem, we could take to the skies in the Aircruise airship concept -- a clipper for the clouds that Seymourpowell showed Wired.co.uk in February 2010, and which Seymour says could become a reality. "I try to maintain an altitude in what I do," he says, adding that much of the technology to create the Aircruise was available 80 years ago. As Seymour states, bringing us back down the ground with a bump, "Technology doesn't hold us back, it's our lack of imagination".

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Early Humans Had Sex With Mysterious Extinct Relatives

Our species may have bred with a now extinct lineage of humanity before leaving Africa, scientists say.

Although we modern humans are now the only surviving lineage of humanity, others once roamed the Earth, making their way out of Africa before our species did, including the familiar Neanderthals in West Asia and Europe and the newfound Denisovans in East Asia. Genetic analysis of fossils of these extinct lineages has revealed they once interbred with modern humans, unions that may have endowed our lineage with mutations that protected them as we began expanding across the world about 65,000 yeas ago.

Now researchers analyzing the human genome find evidence that our species hybridized with a hitherto unknown human lineage even before leaving Africa, with approximately 2 percent of contemporary African DNA perhaps coming from this lineage. In comparison, recent estimates suggest that Neanderthal DNA makes up 1 percent to 4 percent of modern Eurasian genomes and Denisovan DNA makes up 4 percent to 6 percent of modern Melanesian genomes.

"We need to modify the standard model of human origins in which a single population transitioned to the anatomically modern state in isolation — a garden of Eden somewhere in Africa — and replaced all other archaic forms both within Africa and outside Africa without interbreeding," researcher Michael Hammer, a population geneticist at the University of Arizona in Tucson, told LiveScience. "We now need to consider models in which gene flow occurred over time."

Haplotype hints

Hammer and his colleagues gathered DNA samples from the Center for the Study of Human Polymorphisms in Paris and sequenced about 60 regions of the human genome that apparently have no function. These genes are less subject than functional DNA to change as a result of recent evolutionary pressures driving the survival of the fittest; in such a way, they can give a clearer view of how populations might have mixed or not in the past.

The investigators focused on three populations that presented a good sample of the geographic and cultural diversity of sub-Saharan Africa — Mandenka farmers in western Africa, Biaka Pygmies in west-central Africa, and San Bushmen of southern Africa — looking for unusual patterns that suggested ancient interbreeding with other lineages. This included a hunt for long haplotypes, or sets of DNA sequences, not seen in other modern human groups, the idea being that while short haplotypes could potentially be explained by a few chance mutations within these modern human populations, comparatively long haplotypes were instead likely inherited from a significantly different lineage.

 "If interbreeding occurs, it's going to bring in a whole chromosome," Hammer explained. Although this genetic contribution would have dwindled over time, remnants would still exist as shorter, unusual fragments, and "by looking at how long they are, we can get an estimate of how far back the interbreeding event happened." (The longer these odd haplotypes are, the more recently they occurred, having less time to get diminished by other genetic inputs.)

The researchers discovered especially strong evidence for such genetic mixing in the Biaka and San, in the form of a trio of unusual haplotypes. By comparing these sets of genes with those from comparable modern human ones, the investigators estimated the unusual genes may have come from a lineage that first diverged from the ancestors of modern humans about 700,000 years ago. For context, the Neanderthal lineage diverged from ours within the past 500,000 years, while the first signs of anatomically modern human features appeared only about 200,000 years ago.

"The populations that interbred in Africa were on a similar scale of divergence as the expanding modern population and Neanderthals were outside of Africa," Hammer said. "They were similar enough biologically so that they were able to produce fertile offspring, thus allowing genes to flow from one population to the other."

The length of the exotic haplotypes from this extinct lineage suggests interbreeding might still have occurred until as recently as 35,000 years ago.

"We think there were probably thousands of interbreeding events," Hammer said. "It happened relatively extensively and regularly."

Homeland of extinct lineage

A broader survey of where this trio of exotic haplotypes from this extinct lineage might now be found revealed they could be seen in modern human groups across sub-Saharan Africa, but apparently just one central African population of Pygmies, the Mbuti, had all three. Since this group is relatively isolated from other modern human populations, including other Pygmies, the scientists conjecture that central Africa may have been the homeland of this extinct lineage.

In the future, Hammer's team wants to look at the entire genome sequences of several modern human groups in Africa to get a better picture of how interbreeding might have occurred.

"Did it occur in a single burst in a single locale, or was admixture an ongoing process such that genes were flowing over large geographic distances and long periods of time?" Hammer asked. "This has many implications for how modern humans acquired the features that make them unique."

The researchers also want to look for ancient DNA from this extinct lineage that might have conferred some evolutionary advantage to hybrids with modern humans. This process of modern humans interbreeding with other lineages as they expanded across the world "may have accelerated the evolutionary process by allowing genes that are beneficial in one locale to spread to a new population that has not yet had time to adapt to those new conditions," Hammer said. "This may be a major mode of acquiring novel characteristics and one of the ways that we became the species that we are today."

So far no traces of the haplotypes from this newfound lineage have been seen in modern human groups outside of Africa. However, "we can't be sure until we do a better job of searching for them," Hammer said. "Another question for the future."

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Genetic Circuit Force Cancerous Cells To Commit Suicide

Cancer Cell Death This scanning electron micrograph shows a cancer cell in the last stage before it dies. The lumps are from macrophages that have attacked the cancer cell and fused within it.

A new DNA-based logic circuit can sense the signs of cancer, compute that a cell is cancerous, and then cause it to self-destruct, researchers say. The cell-level diagnostic system could be used for drug screening or perhaps for disease treatment, killing tumors while leaving healthy cells alone. 

In principle, the circuit works like any other logic circuit: It analyzes multiple inputs and makes a decision. In this case, the circuit really consists of genes that can detect up to five cancer-specific molecules and their concentrations. When all five of those characteristics are present, the circuit makes a positive determination, and then it triggers cell death.

In a new study, researchers from MIT and ETH Zurich worked with HeLa cells, a prolific type of cervical cancer cell. They studied the cells’ microRNA, which regulates gene expression by destroying messenger RNA, the substance that brings the DNA blueprint to the rest of the cell. They eventually pinpointed one microRNA combo that was unique to HeLa cells. 

This is no small feat by itself — there are about 1,000 versions of miRNA in humans, according to MIT News. Each type of cancer has a unique miRNA profile.

Once they had the right combination, the researchers designed a synthetic gene which codes for a protein that promotes apoptosis, or programmed cell death. The special gene would turn on in the presence of miRNA levels that match the HeLa profile. 

“The biocomputer combines the factors using logic operations such as AND and NOT, and only generates the required outcome, namely cell death, when the entire calculation with all the factors results in a logical TRUE value,” Yaakov Benenson, a professor of synthetic biology at ETH Zurich, said in a statement.

f the miRNA levels were too high or too low, the gene would not switch on, and the cell would not be killed. Healthy cells, which would also lack the HeLa profile, would be similarly left alone, the researchers said.

The next step would be to test this system in a living animal, but this will be difficult. Current methods use viruses or chemicals to bring foreign DNA inside cells, but these make permanent changes, which could have their own complications. So the method is still far from being usable for cancer treatment, researchers said.

Still, it is an important step toward building a single-cell-level diagnostic method, Benenson said. 

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Some New Life Form Lives On Arsenic

• Bacterium in a lab thrived despite substituting one of the six building blocks of life.  


• The finding has implications for the search for life beyond Earth -- as well as the prospect that alternative forms of life may exist on the home planet as well.


• Scientists weaned a strain of bacteriaoff of phosphorus, leaving them to do-or-die with arsenic. Surprisingly, they lived.  

Strange bacteria living deep in a California lake can survive on arsenic and can even grow by incorporating the element into its DNA and cell membranes.

"It has solved the challenge of being alive in a very different way than we knew of," said lead researcher Felisa Wolfe-Simon, a biochemist with the U.S. Geological Survey in Menlo Park, Calif. 

GFAJ-1 is no Frankenstein monster. It's a bacterium scooped up from the salty sediments of Mono Lake in California that seems to have pulled off a major scrambling of its building blocks for life -- something scientists didn't think possible.

The finding not only presents the possibility that alternative life forms can exist, or once existed, on Earth. It opens the floodgates for scientists developing techniques to identify alien life, if it exists. And it raises the prospect of alternative methods for wastewater treatment and bio-energy production.

"The implications are profound, regardless. The building blocks of life are more flexible that we had previously thought," astrobiologist Ariel Anbar, with Arizona State University.

The life forms in question, GFAJ-1 of the Halomonadaceae family of Gamoproteobacteria -- like all living things -- were dependent on oxygen, carbon, hydrogen, nitrogen, phosphorus and sulfur to exist. But in the laboratory of Wolfe-Simon, a NASA astrobiology research fellow, the organisms learned to live with arsenic instead of phosphorus.

"Are the organisms actually doing this in Mono Lake, or do they have the latent ability to do so? That's an interesting question to pursue," said Anbar, a co-author of the study.

Analysis showed the transition was more than cosmetic. The microbes seem to have incorporated arsenic into their DNA. Wolfe-Simon accomplished this by not replenishing the phosphorus in their laboratory environment, forcing them to make do, or die, in a liquid that became increasingly more concentrated in arsenic, which from a molecular perspective, closely resembles phosphorus.

Surprisingly, the colony lived and grew.

 

"Nothing should have grown," Wolfe-Simon told reporters. "It was amazing. We have a microbe doing something different than life as we know it. We've cracked open the door to what's possible elsewhere in the universe."

Steven Benner, with the Foundation for Applied Molecular Evolution in Gainesville, Fla., would like to see more detailed studies on the chemistry, including radioactive tracers to map the location of arsenic in cells.

"Chemists think this is an exceptional result, and therefore chemists will, like Carl Sagan says, require exceptional evidence to prove it," Benner said.

If the study holds up, it could lead to a change in how phosphates are used and managed on Earth.

"Phosphate-based fertilizers are one of the pillars of the green revolution," said chemist James Elser, also with Arizona State. "They are limited in a lot of different ecosystems. Organisms rely on phosphorus to build nucleic acids and other molecules to grow and proliferate."

"Phosphorus is a big issue for sustainability and the quality of aquatic ecosystems. When it leaks out of systems, out of agricultural systems, it functions as a pollutant," Elser added. "It's really exciting to think about the possibilities that are raised by a clever organism that evolved a way to do without phosphorus, possibly... and how it might be used in wastewater treatment, recovering phosphorus from various sources, in bio-energy production."

The finding also will spur NASA to rethink how it goes about looking for life, particularly on Mars, the target for a new rover packed with biology and chemistry experiments that is due to be launched next year.

"It makes me have to expand my notion of what environmental constituents might enable habitability," said Pamela Conrad, a Mars Science Lab co-investigator with NASA's Goddard Space Flight Center in Greenbelt, Md.

"Perhaps arsenic is not an essential component for habitability or for life, but it may be one that can be tolerated," she added. "And that opens up our perspective to try to understand what other potential components might be tolerated, or in fact even essential, that we presently haven't thought of."

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