Atapuerca Mountains Hominins' Nuclear DNA Sequenced, may Push Back Origin of Modern Human, Neandertal Divergence

In a remarkable technical feat, researchers have sequenced DNA from fossils in Spain that are about 300,000 to 400,000 years old and have found an ancestor—or close relative—of Neandertals. The nuclear DNA, which is the oldest ever sequenced from a member of the human family, may push back the date for the origins of the distinct ancestors of Neandertals and modern humans, according to a presentation here yesterday at the fifth annual meeting of the European Society for the study of human evolution.

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DNA Testing Suggests Alaska's North Slope was Ancient Homeland for PreColumbian Arctic North American Peoples

Genetic testing of Iñupiat people currently living in Alaska's North Slope is helping Northwestern University scientists fill in the blanks on questions about the migration patterns and ancestral pool of the people who populated the North American Arctic over the last 5,000 years.

"This is the first evidence that genetically ties all of the Iñupiat and Inuit populations from Alaska, Canada and Greenland back to the Alaskan North Slope," said Northwestern's M. Geoffrey Hayes, senior author of the new study to be published April 29, 2015, in the American Journal of Physical Anthropology.

In this study, all mitochondrial DNA haplogroups previously found in the ancient remains of Neo- and Paleo-Eskimos and living Inuit peoples from across the North American Arctic were found within the people living in North Slope villages.

These findings support the archaeological model that the "peopling of the eastern Arctic" began in the North Slope, in an eastward migration from Alaska to Greenland. It also provides new evidence to support the hypothesis that there were two major migrations to the east from the North Slope at two different times in history.

"There has never been a clear biological link found in the DNA of the Paleo-Eskimos, the first people to spread from Alaska into the eastern North American arctic, and the DNA of Neo-Eskimos, a more technologically sophisticated group that later spread very quickly from Alaska and the Bering Strait region to Greenland and seemed to replace the Paleo-Eskimo," Hayes said.

"Our study suggests that the Alaskan North Slope serves as the homeland for both of those groups, during two different migrations. We found DNA haplogroups of both ancient Paleo-Eskimos and Neo-Eskimos in Iñupiat people living in the North Slope today."

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The RNA World Before DNA Unlocked: RNA Made in its own Mirror Image

A cross-chiral RNA polymerase ribozyme

Authors:

Sczepanski et al

Abstract:

Thirty years ago it was shown that the non-enzymatic, template-directed polymerization of activated mononucleotides proceeds readily in a homochiral system, but is severely inhibited by the presence of the opposing enantiomer. This finding poses a severe challenge for the spontaneous emergence of RNA-based life, and has led to the suggestion that either RNA was preceded by some other genetic polymer that is not subject to chiral inhibition or chiral symmetry was broken through chemical processes before the origin of RNA-based life. Once an RNA enzyme arose that could catalyse the polymerization of RNA, it would have been possible to distinguish among the two enantiomers, enabling RNA replication and RNA-based evolution to occur. It is commonly thought that the earliest RNA polymerase and its substrates would have been of the same handedness, but this is not necessarily the case. Replicating d- and l-RNA molecules may have emerged together, based on the ability of structured RNAs of one handedness to catalyse the templated polymerization of activated mononucleotides of the opposite handedness. Here we develop such a cross-chiral RNA polymerase, using in vitro evolution starting from a population of random-sequence RNAs. The d-RNA enzyme, consisting of 83 nucleotides, catalyses the joining of l-mono- or oligonucleotide substrates on a complementary l-RNA template, and similar behaviour occurs for the l-enzyme with d-substrates and a d-template. Chiral inhibition is avoided because the 106-fold rate acceleration of the enzyme only pertains to cross-chiral substrates. The enzyme’s activity is sufficient to generate full-length copies of its enantiomer through the templated joining of 11 component oligonucleotides.

pop sci write up here.

Harvard & MIT Produce First Nano Foundry...From DNA!

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have unveiled a new method to form tiny 3D metal nanoparticles in prescribed shapes and dimensions using DNA, Nature's building block, as a construction mold.

The ability to mold inorganic nanoparticles out of materials such as gold and silver in precisely designed 3D shapes is a significant breakthrough that has the potential to advance laser technology, microscopy, solar cells, electronics, environmental testing, disease detection and more.

"We built tiny foundries made of stiff DNA to fabricate metal nanoparticles in exact three-dimensional shapes that we digitally planned and designed," said Peng Yin, senior author of the paper, Wyss core faculty member and Assistant Professor of Systems Biology at Harvard Medical School.

The Wyss team's findings, described in a paper titled "Casting Inorganic Structures with DNA Molds," were published today in Science. The work was done in collaboration with MIT's Laboratory for Computational Biology and Biophysics, led by Mark Bathe, senior co-author of the paper.

"The paper's findings describe a significant advance in DNA nanotechnology as well as in inorganic nanoparticle synthesis," Yin said. For the very first time, a general strategy to manufacture inorganic nanoparticles with user-specified 3D shapes has been achieved to produce particles as small as 25 nanometers or less, with remarkable precision (less than 5 nanometers). A sheet of paper is approximately 100,000 nanometers thick.

The 3D inorganic nanoparticles are first conceived and meticulously planned using computer design software. Using the software, the researchers design three-dimensional "frameworks" of the desired size and shape built from linear DNA sequences, which attract and bind to one another in a predictable manner.

"Over the years, scientists have been very successful at making complex 3D shapes from DNA using diverse strategies," said Wei Sun, a postdoctoral scholar in the Wyss' Molecular Systems Lab and the lead author of the paper. For example, in 2012, the Wyss team revealed how computer-aided design could be used to construct hundreds of different self-assembling one-, two-, and three-dimensional DNA nanoshapes with perfect accuracy. It is this ability to design arbitrary nanostructures using DNA manipulation that inspired the Wyss team to envision using these DNA structures as practical foundries, or "molds", for inorganic substances.

"The challenge was to translate this kind of 3D geometrical control into the ability to cast structures in other diverse and functionally-relevant materials, such as gold and silver," Sun said.

Just as any expanding material can be shaped inside a mold to take on a defined 3D form, the Wyss team set out to grow inorganic particles within the confined hollow spaces of stiff DNA nanostructures

The concept can be likened to the Japanese method of growing watermelons in glass cubes. By nurturing watermelon seeds to maturity inside cube-shaped glass boxes, Japanese farmers create cube-shaped mature melons that allow for densely-packed shipping and storage of the fruit.

The Wyss researchers similarly planted a miniscule gold "seed" inside the hollow cavity of their carefully designed cube-shaped DNA mold and then stimulated it to grow. Using an activating chemical solution, the gold seed grew and expanded to fill all existing space within the DNA framework, resulting in a cuboid nanoparticle with the same dimensions as its mold., with the length, width and height of the particle able to be controlled independently.

Next, researchers fabricated varied 3D polygonal shapes, spheres, and more ambitious structures, such as a 3D Y-shaped nanoparticle and another structure comprising a cuboid shape sandwiched between two spheres, proving that structurally-diverse nanoparticles could be shaped using complex DNA mold designs.

Given their unthinkably small size, it may come as a surprise that stiff DNA molds are proportionally quite robust and strong, able to withstand the pressures of expanding inorganic materials. Although the team selected gold seedlings to cast their nanoparticles, there is a wide range of inorganic nanoparticles that can be forcibly shaped through this process of DNA nanocasting.

link.

Is It Mom or Dad's Fault, ahem, DNA?

A new technique successfully takes on a longstanding challenge in DNA sequencing – determining whether a particular genetic sequence comes from an individual's mother or father. The method, described in a Ludwig Cancer Research study in Nature Biotechnology, promises to accelerate studies of how genes contribute to disease, improve the process of matching donors with organs and help scientists better understand human migration patterns.

"The technique will enable clinicians to better assess a person's individual risk for disease. It is potentially transformative for personalized medicine," says Bing Ren, Ludwig scientist at the University of California, San Diego School of Medicine, who led the research on the new technique, called "HaploSeq."

"Current sequencing technologies are fast and rapidly getting cheaper – an individual's genome can now be sequenced in about a week for $5,000," says Ren. "In the not too distant future, everyone's genome will be sequenced. That will become the standard of care." But, he explains, "There has been a problem with this scenario." Except for the sex chromosomes, everyone has two copies of each chromosome. One copy comes from mom, and the other from dad. Current techniques cannot distinguish between the two copies of each gene and, therefore, are not very good at determining whether particular genetic differences, such as a single-letter change in the DNA, originate with an individual's mother or father – muddying genetic analyses.

Ren's new technique, a mixture of molecular biology and computational biology approaches, bypasses this problem. The method enables researchers to quickly determine which genetic variants occur together on the same stretch of chromosome and, therefore, came from the same parent. "This advance has direct implications for the utility of genomics in clinical practice and will also have profound effects on genetic research and discovery," says Ludwig scientist Siddarth Selvaraj, who contributed to the study with Ren and fellow Ludwig researcher Jesse Dixon.

More immediately, the technique will enable clinicians to better assess a person's individual risk for disease, a cornerstone of personalized medicine. For instance, people at risk for a disease such as cancer often have more than one DNA mutation. HaploSeq could enable clinicians to determine if the two mutations are on the same chromosome or on different chromosomes, which can help in risk assessment – for instance, risk may be reduced if two mutations are on the same chromosome, since the 'good' chromosome can often compensate.

Similarly, the method, with further honing, has the potential to refine the currently cumbersome process of determining whether there is a genetic match between an organ donor and recipient. A large number of genes contribute to compatibility between donor and recipient, but there is a lot of genetic variability in these genes. The new technique could help determine whether DNA differences between donor and recipient are likely to be a good match. "This will require more study," says Ren, "but by creating a DNA database, it may be possible to more accurately and expediently pair recipients and donors."

The new method will also help researchers analyze human migration and determine ancestry from their DNA sequences. "In principal," says Ren, "you could compare your genetic sequence to your neighbor's and ask if you have any recent ancestors in common. With our technique we can study each individual and how they relate to other individuals. As we accumulate data from many individuals we can more precisely determine their relationships." Such findings will also bolster an ongoing international project to assess worldwide human genetic variation, the HapMap project.

link.

Using Amber to Create Jurassic Park Is Impossible

It is hardly possible to talk about fossil insects in amber without the 1993 movie Jurassic Park entering the debate. The idea of recreating dinosaurs by extracting DNA from insects in amber has held the fascination of the public for two decades. Claims for successful extraction of DNA from ambers up to 130 million-years-old by various scientists in the early 1990s were only seriously questioned when a study at the Natural History Museum, London, was unable to replicate the process. The original claims are now considered by many to be a text-book example of modern contaminant DNA in the samples. Nonetheless, some scientists hold fast to their original claims.

Research just published in the journal The Public Library of Science ONE (PLOS ONE) by a team of researchers from the Faculty of Life Sciences at The University of Manchester can now confirm that the existence of DNA in amber fossils is highly unlikely. The team led by amber expert Dr David Penney and co-ordinated by ancient DNA expert Professor Terry Brown used highly-sensitive 'next generation' sequencing techniques – the most advance type of DNA sequencing - on insects in copal, the sub-fossilized resin precursor of amber.

The research was conducted wearing full forensic suits in the dedicated ancient DNA facility at The University of Manchester, which comprises a suite of independent, physically isolated laboratories, each with an ultra-filtered air supply maintaining positive displacement pressure and a managed access system.

According to Professor Brown: "In the original 1990s studies DNA amplification was achieved by a process called the polymerase chain reaction (PCR), which will preferentially amplify any modern, undamaged DNA molecules that contaminate an extract of partially degraded ancient ones to give false positive results that might be mistaken for genuine ancient DNA. Our approach, using 'next generation' sequencing methods is ideal for ancient DNA because it provides sequences for all the DNA molecules in an extract, regardless of their length, and is less likely to give preference to contaminating modern molecules."

The team concluded that their inability to detect ancient DNA in relatively young (60 years to 10,600 years old) sub-fossilized insects in copal, despite using sensitive next generation methods, suggests that the potential for DNA survival in resin inclusions is no better, and perhaps worse, than that in air-dried museum insects (from which DNA has been retrieved using similar techniques). This raises significant doubts about claims of DNA extraction from fossil insects in amber, many millions of years older than copal.

link.

paper link.

Paleo Viruses in Our "Junk" DNA Have Role in Natal Development and Cancer

The St. Laurent Institute, a non-profit medical research institute focused on the systems biology of disease, today announced in a study published in the July edition of Genome Biology, that genetic matter, previously ignored by the scientific community, may play an important role in cancer. The study, "VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer" found that novel non-coding parts of the human genome known as vlincRNAs (very long intergenic, non-coding RNAs) triggered by ancient viruses, participate in the biology of stem cells, and in the development of cancer. Importantly, the group of researchers from U.S., Europe and Russia found that the elimination of these vlincRNAs caused the death of cancer cells.

"Understanding this previously ignored part of the human genome, its role in human development, and how it may be taken over by disease, opens a new frontier in science with important implications for medical advances," said Philipp Kapranov, Ph.D., lead researcher at the St. Laurent Institute. "Future research into the role and function of vlincRNAs holds promise for both highly targeted diagnostic tests and more precise cancer treatments.

Up to 98 percent of human genomic matter is known as "junk" or "dark matter" non-coding DNA, and had for years attracted little interest among scientists who doubted its role in human health and disease. Recent research has begun to identify that part of that non-coding DNA is used by the cell to make RNA such as vlincRNA, highly tissue-specific RNA chains of unusually large lengths, many of which are only found in embryonic or cancerous cells. VlincRNAs found in these two types of cells tend to be expressed based upon genetic signals from ancient viruses that invaded our ancestors' genome millions of years ago and were gradually "domesticated" over evolutionary time. The number of vlincRNAs expressed by these domesticated viral sequences correlates with both embryonic development and malignant cancers.

Quadruplex DNA Observed in Cells

There is no more iconic image in biology than that of DNA's double-stranded helix, which coils and supercoils on itself to form dense chromosomes.

But a quite different, square-shaped type of DNA structure can easily be created in the laboratory by the folding of synthetic DNA strands rich in guanine, one of the building blocks of DNA. Scientists have long believed that these so-called 'G-quadruplex structures' may occasionally form in the DNA of living cells. A G-quadruplex comprises four guanines from different places along a G-rich strand held together by a special type of hydrogen bonding to form a compact square structure that interrupts the DNA helix.

In a paper published online today in Nature Chemistry, researchers led by Shankar Balasubramanian at the University of Cambridge, UK, provide strong evidence that G-quadruplexes do occur in cells — and that these unusual structures may have important biological functions.

Multi stranded DNA molecules can no longer be called alien.

New Clues to the RNA-based World That Came Before

In modern biology, all life, with the exception of some viruses, uses DNA as its genetic storage mechanism. According to the "RNA-world" hypothesis, RNA appeared on Earth first, serving as both the genetic-storage material and the functional molecules for catalyzing chemical reactions, then DNA and proteins evolved much later. Unlike DNA, RNA can adopt many different molecular conformations and so it is functionally interactive on the molecular level. In the soon-to-be-published research paper, two professors of chemistry, Christine Keating and Philip Bevilacqua, and two graduate students, Christopher Strulson and Rosalynn Molden, probe one of the nagging mysteries of the RNA-world hypothesis.

"A missing piece of the RNA-world puzzle is compartmentalization," Bevilacqua said. "It's not enough to have the necessary molecules that make up RNA floating around; they need to be compartmentalized and they need to stay together without diffusing away. This packaging needs to happen in a small-enough space -- something analogous to a modern cell -- because a simple fact of chemistry is that molecules need to find each other for a chemical reaction to occur."

To test how early cell-like structures could have formed and acted to compartmentalize RNA molecules even in the absence of lipid-like molecules that make up modern cellular membranes, Strulson and Molden generated simple, non-living model "cells" in the laboratory. "Our team prepared compartments using solutions of two polymers called polyethylene glycol (PEG) and dextran," Keating explained. "These solutions form distinct polymer-rich aqueous compartments, into which molecules like RNA can become locally concentrated."

The team members found that, once the RNA was packed into the dextran-rich compartments, the molecules were able to associate physically, resulting in chemical reactions. "Interestingly, the more densely the RNA was packed, the more quickly the reactions occurred," Bevilacqua explained. "We noted an increase in the rate of chemical reactions of up to about 70-fold. Most importantly, we showed that for RNA to 'do something' -- to react chemically -- it has to be compartmentalized tightly into something like a cell. Our experiments with aqueous two-phase systems (ATPS) have shown that some compartmentalization mechanism may have provided catalysis in an early-Earth environment."

Keating added that, although the team members do not suggest that PEG and dextran were the specific polymers present on the early Earth, they provide a clue to a plausible route to compartmentalization -- phase separation. "Phase separation occurs when different types of polymers are present in solution at relatively high concentrations. Instead of mixing, the sample separates to form two distinct liquids, similar to how oil and water separate." Keating explained. "The aqueous-phase compartments we manufactured using dextran and PEG can drive biochemical reactions by increasing local reactant concentrations. So, it's possible that some other sorts of polymers might have been the molecules that drove compartmentalization on the early Earth." Strulson added that, "In addition to the RNA-world hypothesis, these results may be relevant to RNA localization and function in non-membrane compartments in modern biology."

The team members also found that the longer the string of RNA, the more densely it would be packed into the dextran compartment of the ATPS, while the shorter strings tended to be left out. "We hypothesize that this research result might indicate some kind of primitive sorting method," Bevilacqua said. "As RNA gets shorter, it tends to have less enzyme activity. So, in an early-Earth system similar to our dextran-PEG model system, the full-length, functional RNA would have been sorted and concentrated into one phase, while the shorter RNA that is not only less functional, but also threatens to inhibit important chemical reactions, would not have been included."