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News Article | May 16, 2017
Site: www.sciencenews.org

Face-to-face, a human and a chimpanzee are easy to tell apart. The two species share a common primate ancestor, but over millions of years, their characteristics have morphed into easily distinguishable features. Chimps developed prominent brow ridges, flat noses, low-crowned heads and protruding muzzles. Human noses jut from relatively flat faces under high-domed crowns. Those facial features diverged with the help of genetic parasites, mobile bits of genetic material that insert themselves into their hosts’ DNA. These parasites go by many names, including “jumping genes,” “transposable elements” and “transposons.” Some are relics of former viruses assimilated into a host’s genome, or genetic instruction book. Others are self-perpetuating pieces of genetic material whose origins are shrouded in the mists of time. “Transposable elements have been with us since the beginning of evolution. Bacteria have transposable elements,” says evolutionary biologist Josefa González. She doesn’t think of transposons as foreign DNA. They are parts of our genomes — like genes. “You cannot understand the genome without understanding what transposable elements are doing,” says González, of the Institute of Evolutionary Biology in Barcelona. She studies how jumping genes have influenced fruit fly evolution. Genomes of most organisms are littered with the carcasses of transposons, says Cédric Feschotte, an evolutionary geneticist at the University of Utah in Salt Lake City. Fossils of the DNA parasites build up like the remains of ancient algae that formed the white cliffs of Dover. One strain of maize, the organism in which Nobel laureate Barbara McClintock first discovered transposable elements in the 1940s, is nearly 85 percent transposable elements (SN: 12/19/09, p. 9). Corn is an extreme example, but humans have plenty, too: Transposable elements make up nearly half of the human genome. Most of the transposons in the genomes of humans and other creatures are now “dead,” meaning they are no longer able to jump. The majority are in bits and pieces scattered throughout the genome like so much confetti. Many researchers used to think these broken transposons were just genetic garbage. Far from junk, however, jumping gene remnants have been an evolutionary treasure trove. Some of the control switches transposons once used for their own hopping have been recycled over time into useful tools that help species, including Homo sapiens, adapt to their environments or take on new characteristics. Repurposed transposon parts are at the very heart of what makes humans human, says Gennadi Glinsky, a cancer biologist at the University of California, San Diego. Some of the first genes to turn on in early human embryos are transposon remains that now help direct embryonic development. We humans also owe parts of our immune system, and perhaps our brainpower, to transposable elements. “Without them, we simply wouldn’t exist,” Glinsky says. Transposons have shaped the evolution of nearly every organism on Earth. Here are just a few examples of their effects. The evolutionary benefits might delude some people into thinking that transposons are friends, but don’t be fooled, Feschotte says. “They are not there to make us happy.” Transposons have only ever served one purpose: to make more of themselves. Transposons have two main ways of propagating: copy and paste or cut and paste. Retrotransposons — many of which were once RNA viruses called retroviruses — are the copy-and-pasters. They insert into an organism’s DNA, get copied into many RNA replicas and then use a special enzyme called a retrotransposase to convert the RNA copies back into DNA. Those DNA duplicates can hop into different spots in the genome. Retrotransposons, the most common type of transposable element in humans, make up about 45 percent of the human genome. Instead of making copies, DNA transposons use the cut-and-paste method to move around the genome. To hop, they slice themselves out of the DNA and move to a new location. Sometimes cells make copies of these transposons while attempting to repair damage created when the transposons sliced the DNA. But because they don’t actively copy themselves, DNA transposons are greatly outnumbered by retrotransposons, making up only about 4 percent of the human genome. Like any invader, a live transposon can spell problems for its host. Both types of transposons may disrupt important genes as they bounce around the genome, says pathologist Kathleen Burns. As far as scientists know, there’s only one living transposon left in the human genome, says Burns, of Johns Hopkins University School of Medicine. A retrotransposon known as LINE-1, or long interspersed element-1, is still hopping. It has deposited so many copies of itself that it accounts for about 18 percent of the human genome. Another transposon called an Alu element can’t move on its own, but it gets around by hitching rides from LINE-1. “If LINE-1 is a parasite of the genome, then Alu is a parasite’s parasite,” says John Moran, a geneticist at the University of Michigan in Ann Arbor. And a very successful one. Each person carries more than 1 million spots where an Alu element has landed, leaving behind a full or partial copy of itself. All together, scattered bits and pieces of Alu make up about 11 percent of human DNA. “Just by sheer mass alone they’ve contributed greatly to the size of our genome,” he says. LINE-1 and Alu aren’t prolific bounders. Even when they do move, most LINE-1 and Alu hops are inconsequential, Burns says — but not always. Scientists have long known that when LINE-1 jumps into a gene called APC, it can disrupt the gene and lead to colon cancer. A jump that disrupts a gene encoding a blood-clotting protein called factor VIII can cause the bleeding disorder hemophilia A. Production of one of LINE-1’s proteins called ORF1p is a hallmark of cancer, Burns and colleagues reported in 2014 in the American Journal of Pathology. As pancreatic tumors grow and evolve, they collect LINE-1 insertions, Burns and colleagues reported in Nature Medicine in 2015. On average, the pancreatic cancer patients examined in the study carried 15 LINE-1 insertions in their tumor DNA that were not in healthy tissue. Some people carried no new insertions, others had up to 65. Cancer isn’t the only disease in which LINE-1 and Alu are suspects. In brain cells, Alu has repeatedly jumped into DNA associated with a gene called TOMM40. Alu’s shenanigans may keep TOMM40, which helps cellular power plants called mitochondria run, from doing its job. That could put stress on cells with weakened mitochondria, making them vulnerable to degenerative diseases such as Alzheimer’s, geneticist Peter Larsen of Duke University and colleagues proposed February 24 in Alzheimer’s & Dementia. But transposon jumping might have a plus side. “We believe that some level of activity is important for a healthy brain,” says neuroscientist and geneticist Jennifer Erwin. LINE-1 hops frequently in the human brain, Erwin found while at the Salk Institute for Biological Studies in La Jolla, Calif. She and colleagues examined DNA from individual brain cells taken from three donated human brains and tested bulk samples from the hippocampus (an area important for learning and memory) and the frontal cortex (where most thinking and decision making is thought to happen). Brain cells in those areas did not have identical DNA. LINE-1 jumped to new places in some cells or was removed from places in others, the team reported last year in Nature Neuroscience. LINE-1 variations affect 44 to 63 percent of cells in the brain, the researchers estimated. Some transposon hopping may be a reaction to stress, says Erwin, now at Johns Hopkins University. “We think of it as a way for the genome to adapt to unknown pressures and environments.” Each jump is a bit of a gamble, with potentially good or bad consequences, she says. But rolling the dice with transposon hopping may allow brain cells to develop capabilities not initially encoded in the genome. Those new capacities may influence behavior, thinking and personality. Glinsky goes further, contending that transposons help individualize people. Even identical twins may have genetically different brain cells because of transposon hopping after the embryo splits, he says. Thanks to jumping genes, “Every time a human baby is created, you make an individual that can never be replicated.” Most of the 950,000 or so copies of LINE-1 in the human genome are partial copies or contain mutations that put an end to their jumping. Only about 100 are full copies that actually jump. Eventually, natural selection or chance may rid the genome of damaging insertions, leaving the partial, inactive LINE-1 skeletons (or Alu) scattered throughout the genome. All other human transposable elements have already met that fate. Human genomes are veritable boneyards of transposon fossils. But even relics that no longer jump can still have an effect on human evolution. Some of those fossils have been passed down from very early human ancestors. Some were inherited from ancestors of all four-limbed vertebrates. Those jumping genes got stuck in the ancient host’s DNA hundreds of millions of years ago. By now, their fossils are mere shards, torn apart in the natural shuffling of DNA as each generation bequeaths slightly different genetic combinations to its heirs. Some of those shards have proved useful, helping to shape important novelties, such as pregnancy in mammals (SN Online: 1/29/15). “These elements have a lot to do with genome innovation,” says Ting Wang, a geneticist at Washington University in St. Louis. Some long-dead transposon remnants have been transformed into both small and large RNAs. Not the kind that encode proteins, but RNAs that help boost or dampen protein production and gene activity in cells, and have been linked to health and disease (SN: 8/28/10, p. 18). Like flea market furniture, old transposons have been up-cycled into at least 409 small RNAs called microRNAs, Sheng Qin of Nanjing Normal University in China and colleagues reported in PLOS ONE in 2015. Other researchers have found that more than 30 percent of long noncoding RNAs — which carry out several different jobs in the cell, most still unknown — are repurposed transposable elements (SN: 12/17/11, p. 22). A plethora of other small RNAs were originally transposable elements themselves, but have now been co-opted to keep transposons from jumping. RNAs aren’t the only valuable salvage items humans have pulled from the transposon junk pile. Some proteins recycled from jumping gene parts have also proved extremely useful, especially for the immune system. Researchers had long suspected that two DNA-cutting enzymes called RAG1 and RAG2 are encoded by relics of a DNA transposon, but no one had ever found a transposon that uses those proteins to slice and hop out of a spot, says immunologist Anlong Xu of Sun Yat-sen University in Guangzhou, China. The enzymes are important because they generate antibodies and other immune proteins needed to recognize and kill an ever-changing variety of infectious organisms. Working with small, fishlike and jawless creatures called lancelets, Xu and colleagues found a DNA transposon called ProtoRAG, an evolutionary relative of the genes for the mammalian immune system’s RAG1 and RAG2. The finding suggests the DNA transposon that gave rise to the two enzymes jumped into an ancestor of lancelets and jawed vertebrates about 550 million years ago. The transposon was passed down generation after generation until jawed vertebrates borrowed the RAG enzymes to make new immune proteins, Xu and colleagues proposed last summer in Cell. Perhaps the most valuable scraps in the transposable element junk heap are bits of DNA called transcription factor binding sites. Transcription factors are proteins that help control gene activity, usually turning it up a notch or two. Each type of transcription factor recognizes and binds to a certain sequence of DNA. Upon binding to DNA, transcription factors work with other proteins to stimulate the process of copying DNA instructions into RNA to ultimately make proteins. Transcription factors control genes in complex networks reminiscent of the electronic circuits that drive computers. Such circuits would be very difficult to evolve from scratch, Wang says. Thanks to transposons, humans didn’t have to. Retrotransposons are littered with transcription factor binding sites, which might be expected for entities that make their living by getting copied into RNA over and over again. Broken transposons can provide raw materials that over time become complex gene-regulating switches. Many of the transcription factor binding sites important for controlling human and mouse genes may have come from transposable elements, research by Wang and colleagues suggests. Some of these recycled transposon bits may have helped humans fight viruses. About 45 million to 60 million years ago, a retrovirus called MER41 invaded the genome of a primate ancestor of humans. Today, humans have hundreds of copies of the now-extinct retrovirus scattered about their genomes. Other mammals, such as lemurs, vesper bats, carnivores and even-toed ungulates, have MER41 relatives in their genomes, too, Feschotte and colleagues reported last year in Science. What’s important about the discovery is that MER41’s bits and pieces include binding sites for transcription factors involved in fighting infections. Those transcription factors are alerted to infection by an immune system chemical called interferon gamma. The researchers speculate that the retrovirus may have used the interferon gamma signal to boost its own production. But over time, the mammalian hosts turned that weapon against the virus. By reconfiguring genetic circuits, transposons have helped to make humans uniquely human, Glinsky says. Rewiring gene activity in humans happened, in part, when transposons inserted themselves into the genomes of human ancestors after the split from chimpanzees, he reported last year in Genome Biology and Evolution. Remains of the transposons that infected humans have been recycled into more than a thousand regulatory switches found only in humans, he discovered. Developmental biologist Joanna Wysocka of Stanford University has also been interested in what all the left-behind transposon bits might be doing in humans, particularly in the earliest stages of human development. Usually the DNA around jumping genes is heavily marked with molecules known as methyl groups. DNA methylation usually turns genes off — silencing them like a strip of tape across the mouth. The molecular tape also helps keep the transposons from hopping around and doing damage. Early in development, though, the silencing tape is ripped away, leaving genes unmarked and ready for action. Some of the first genes to start expressing themselves again are former viruses turned into transposable elements known as human endogenous retroviruses, particularly one called HERVK, Wysocka and colleagues found. HERVK is the youngest class of endogenous retroviruses: They were last active as viruses within the last 200,000 years. Those glory days are long gone. HERVK can no longer make infectious viruses because each copy of the virus has some mistake that renders it harmless. But some of HERVK’s damaged genes can still make proteins, albeit defective ones. And some of those defective proteins may actually assemble into viruslike particles that can help protect human embryos, Wysocka and colleagues reported in 2015 in Nature. Those viruslike particles may activate a primitive virus-fighting system that could help defend embryos from other, more dangerous infections before the immune system or placenta are available to do so, Wysocka thinks. That sounds like a possible evolutionary game-winner, but Wysocka says there are other options. The system “could be an evolutionary accident that human development now has to cope with,” she says. But regardless of its evolutionary role, scientists need to understand what retroviruses and other transposons are doing to shape human development. Wysocka and colleagues have found evidence of transposons sculpting human faces. The researchers used cells from humans and chimpanzees that had been reprogrammed to behave like stem cells. Those reprogrammed stem cells were then coaxed to become cranial neural crest cells, which help form the face. Examining gene activity in these cells allowed Wysocka and colleagues to do “cellular anthropology” to figure out how human and chimp facial development differs, the team reported in Cell in 2015. The researchers discovered that hundreds of gene regulatory switches known as enhancers are used differently in the two species. Many of those enhancers are bits of former endogenous retroviruses, versions of LINE-1 or other retrotransposons. A recycled retrotransposon fragment that Wysocka’s team calls “Coordinator” was often found at enhancers that showed variable gene activity between chimps and humans. Just a few mutations could turn a piece of old transposon into something that flips on gene activity, the researchers found. Humans evolved Coordinator mutations that are good at turning on human versions of genes, but not so great at turning on chimp genes. Chimp Coordinators, on the other hand, easily turn on chimp genes but don’t work as well for human genes. Humans’ extinct relatives, the Neandertals and Denisovans, had Coordinator elements similar to those in modern humans, but a few small changes were found only in modern humans, the researchers reported. Exploring those differences could tell the researchers more about the family resemblance between modern humans and those extinct cousins. It’s hard to quantify exactly how important transposons have been to human evolution, Feschotte says. But it seems that everywhere researchers look, jumping genes have left their marks. This article appears in the May 27, 2017, issue of Science News with the headline, "The Difference Makers: Transposons sculpt our genomes, for good or bad."

News Article | May 3, 2017
Site: www.eurekalert.org

Fishes perceive changes in water currents caused by prey, conspecifics and predators using their lateral line. The tiny sensors of this organ also allow them to navigate reliably. However, with increasing current velocities, the background signal also increases. Scientists at the University of Bonn have now created a realistic, three-dimensional model of a fish for the first time and have simulated the precise current conditions. The virtual calculations show that particular anatomical adaptations minimize background noise. The results are now being presented in the Journal of the Royal Society Interface. The ide (Leuciscus idus) is a fish that inhabits the lower stretches of slow-flowing rivers. Like most fishes, it can perceive the current using its lateral line. The mechanoreceptors of this organ are distributed over the surface of the entire body, which is why the organ provides a three-dimensional image of the hydrodynamic conditions. Fishes can thus also find their way around themselves in the dark and identify prey, conspecifics, or predators. The recently retired zoologist Prof. Horst Bleckmann from the University of Bonn has spent many years researching the sensitive organ and has used it as inspiration for technical flow sensors in order to, for instance, identify leakages in water pipes. The scientists Dr. Hendrik Herzog from the Institute of Zoology and Dr. Alexander Ziegler from the Institute of Evolutionary Biology and Ecology at the University of Bonn have now entered a new dimension of research into the lateral line in fish: they created the first realistic, three-dimensional computer model of the lateral line system, which they used to calculate the precise flow conditions of the surrounding water. "We concentrated on the head of the ide, because the lateral line of the fish has a particularly complex form there," reports Dr. Herzog. This organ has two different types of sensors. Some protrude like small bumps from the surface of the fish's skin and the water flows directly over them. Others sit in canals that are submerged into the cranial bone and are connected to the water via small pores. "If prey, such as a freshwater shrimp, is close by, the local water current and pressure conditions change," explains Dr. Ziegler. The fish registers this with its many sensors. "However, until now, the actual function of such different types of current measurement had not been clarified conclusively." Both researchers received active support from Birgit Klein from the Westphalian University of Applied Sciences. In her bachelor thesis at the Institute of Zoology, the current master student compared various methods of 3D reconstruction. She took around 350 photos of the head of the ide from various angles and used them to produce a 3D model of the fish surface. She had dyed the channels and sensors of the lateral line beforehand, which is why the structures in the model can be clearly identified. She then optimized the dataset by digitizing the fish head using a much higher-resolution laser scanning procedure. This created a realistic image of the fish surface, but the inside of the animal was not recorded in this way. This is why the researchers used a micro-computed tomography scanner as the third method. A contrast agent allowed the soft tissue to be shown even when using this X-ray technique. At the end, data from all three techniques flowed into the realistic model of the lateral line. The zoologists thus simulated various current conditions and calculated the hydrodynamic signals to the various sensors. A strong current is a challenge for the fish, as the background noise for the sensors is particularly great. Nevertheless, the fish can precisely perceive its environment even with high water speeds. As the researchers show with their calculations, depressions ensure that the current is significantly reduced for the bump-like sensors that sit on the surface of the skin. "The relative signal strength of, for instance, prey organisms thus becomes greater," explains Dr. Herzog. For the sensors in the channels, it was shown that certain sections of the lateral line are particularly sensitive to the respective current strength due to different channel diameters. "Using our methodical approach, comparative anatomical studies between different fish species with an especially high level of detail will be possible in the future," reports Dr. Ziegler. His colleague sees bio-inspired applications in the foreground: "The knowledge from such 3D models of fish may also make it possible to significantly improve the autonomous navigation of underwater robots using flow sensors," suggests Dr. Herzog. Publication: Form and function of the teleost lateral line revealed using three-dimensional imaging and computational fluid dynamics, the Journal of the Royal Society Interface, DOI: http://dx. Dr. Alexander Ziegler Institute of Evolutionary Biology and Ecology University of Bonn Tel. +49 (0)228/735758 E-mail: aziegler@evolution.uni-bonn.de

News Article | May 1, 2017
Site: www.gizmag.com

When life gives you an ancient cave filled with dirt, look for DNA. That's what paleontologists and those involved in the study of ancient humans will likely be doing in the future following the revelation of a breakthrough technique that enables hominin DNA to be recovered directly from sediments without the need for fossils. Led by geneticist Viviane Slon as well as molecular biologist Matthias Meyer (both from Germany's Max Planck Institute for Evolutionary Anthropology), the team is the first to extract Neanderthal and Denisovan DNA directly from dirt samples collected from archaeological caves in Europe where their existence has been documented. More interestingly, they were also able to recover DNA at sites where no bones were ever found. All living things leave behind genetic traces of themselves as they go through life, and our ancient ancestors were no different. One of the advantages of using this "eDNA" (environmental DNA) to study ecosystems and the animals living in them is that all it requires is a water or soil sample. Unsurprisingly, scientists have been applying this technique to prehistoric animals – evolutionary geneticist Eske Willersev made headlines back in 2003 when he became the first scientist to sequence the DNA from species such as woolly mammoths from Serbian permafrost. However this doesn't make the new findings any less of a feat given how difficult it is to isolate ancient human DNA. For a start, there's the fact that it exists in minuscule traces from decomposed bodies, blood or feces, which often get lost among the other biological material in the soil. Secondly, there's the difficulty of distinguishing it from modern human DNA, which inevitably ends up contaminating samples when researchers handle them. Sure enough, while it wasn't a problem identifying the DNA of extinct animal species such as the woolly mammoth and woolly rhinoceros in the sediment samples that they collected, identifying ancient human DNA required a far greater degree of precision. "From the preliminary results, we suspected that in most of our samples, DNA from other mammals was too abundant to detect small traces of human DNA," says Slon. "We then switched strategies and started targeting specifically DNA fragments of human origin." As documented in their study, they developed a molecular probe based on modern human mitochondrial DNA – which was chosen due to its abundance – to extract similar sequences. The researchers then compared the samples they found to known variants associated with Neanderthals or Denisovans and checked for chemical damage consistent with ancient DNA to make sure that they were looking at the right genetic material. To prevent modern human DNA from contaminating the sediments, archaeologists working at the El Sidrón cave in Spain, one of the sites in the study, also developed a protocol called "clean excavation" that enables researchers to extract both nuclear and mitochondrial DNA from teeth and skeletal remains for comparison purposes. The result: Not only were the researchers able to detect the presence of ancient hominin DNA in the sediment samples from four caves, they were also able to distinguish between species and even deduce when a specific group might have occupied a cave. "This work represents an enormous scientific breakthrough," explains paleontologist Antonio Rosas from the Natural Science Museum in Madrid, who was part of the study. "We can now tell which species of hominid occupied a cave and on which particular stratigraphic level, even when no bone or skeletal remains are present." Case in point: The researchers found that the Denisovans and Neanderthals had occupied the Denisova Cave at different points in time based on the soil layer in which their DNA was found. "The Denisovans appear in the bottommost stratum, that is, in the oldest of the deposits," says Rosas. "Their DNA in this sediment, without being associated with any skeletal remains, is the oldest proof of their existence right now." At the Trou Al'Wesse Cave in Belgium, while bones have never been found, Neanderthal stone tools have long hinted at their creators' existence. Thanks to this technique, the researchers were finally able to confirm that they had once occupied the site with the extraction of Neanderthal DNA from the sediments. Given the results of the study, it's no wonder researchers such as Svante Pääbo, the esteemed evolutionary geneticist who was also involved in the study, say it could very well become a routine archaeological procedure for studying sites where no human remains have been found. And even in cases where there are hominin fossils, this technique could still be of use since it can extract DNA without causing any damage. More importantly, this technique could help scientists fill in the gaps in our knowledge regarding our ancient ancestors: What routes did they take on their way to colonizing different parts of the world? How did different ancient human species co-exist? Though the findings have shed more light on the enigmatic Denisovans, they have also raised even more questions in turn. Their DNA was found in only one cave. However recent studies have shown their genes to be present in Tibetans and Sherpas, which could explain their ability to live in high-altitude environments. Did the Denisovans ever leave their cave and if so, where did they go? "The technique could increase the sample size of the Neanderthal and Denisovan mitochondrial genomes, which until now were limited by the number of preserved remains," adds scientist Carles Lalueza-Fox from the Institute of Evolutionary Biology in Barcelona. "And it will probably be possible to even recover substantial parts of nuclear genomes." The study has been published in Science.

News Article | April 28, 2017
Site: www.techtimes.com

Researchers often look for ancient bones and teeth in a bid to learn more about extinct human relatives, but for the first time, scientists were able to detect DNA from the Neanderthals and the Denisovans in ancient muds in caves even without the skeletal remains of these individuals. The work suggests it is possible for scientist to detect the DNA of extinct human lineages in places with no skeletal remains. If verified, the technique they used may help fill the gap on current understanding of the evolution of humans given the difficulty in finding skeletal remains of extinct human relatives. The mysterious Denisovans and the Neanderthals are believed to have a common ancestor that split from the lineage of modern humans about 765,000 years ago. Since DNA binds to the mineral component of bones, geneticist Matthias Meyer, from Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and colleagues conducted an investigation to determine if the same could happen in ancient sediments full of minerals. The researchers conducted an analysis of 85 samples of sediments hailing back from 14,000 to 550,000 years ago. The samples were collected from seven different sites where earlier research suggested ancient humans once lived. Included in these sites is the Denisova Cave, where the first fossils of the Denisovans were discovered. The researchers used a special technique that looks for mitochondrial DNA of mammals. To ensure that they do not get modern genetic materials, Meyer and colleagues only analyzed the short sequences marked by chemical damage that typically characterize ancient DNA. Researchers were able to identify DNA from a number of animals that include woolly mammoths and cave bears, but mixed in with these animal DNA were traces of human DNA. They found Neanderthal DNA in four caves and the Denisovan DNA in Siberia's Denisova Cave. "Using targeted enrichment of mitochondrial DNA we show that cave sediments represent a rich source of ancient mammalian DNA that often includes traces of hominin DNA, even at sites and in layers where no hominin remains have been discovered," the researchers wrote in their study published in the journal Science on April 27. "Our work opens the possibility to detect the presence of hominin groups at sites and in areas where no skeletal remains are found." One problem about this technique is that DNA may seep across layers of sediments, so it is difficult to know the time when the extinct humans lived at a particular site. The exact sources of the DNA are not also clear. The DNA may have come from fecal matter, body fluids, hair, and bones, but researchers currently have no way of telling the exact source of the genomes. "The technique could increase the sample size of the Neanderthal and Denisovan mitochondrial genomes, which until now were limited by the number of preserved remains. And it will probably be possible to even recover substantial parts of nuclear genomes", said Carles Lalueza-Fox, from the Institute of Evolutionary Biology. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.

News Article | December 15, 2016
Site: www.eurekalert.org

Genomic analysis of the Iberian lynx confirms that it is one of the species with the least genetic diversity among individuals, which means that it has little margin for adaptation Spanish scientists have sequenced the genome of the Iberian lynx (Lynx pardinus), currently one of the world's most endangered felines. They have confirmed the "extreme erosion" suffered by its DNA. The Iberian lynx has one of the least genetically-diverse genomes. It is even less diverse than other endangered mammals, such as the cheetah or Tasmanian devil, or birds, like the crested ibis or osprey. The study, being published today in the scientific journal Genome Biology, has been coordinated by scientists from the Doñana Biological Station (CSIC). The Centre for Genomic Regulation (CRG) contributed to this research project from the very beginning including several groups and facilities. In particular, the laboratories of Roderic Guigó, Cedric Notredame, and Toni Gabaldón at the Bioinformatics and Genomics Programme as well as the CRG Bioinformatics unit. This is the first mammal genome of reference generated entirely in Spain. The project, financed by Banco Santander and managed by the Fundación General CSIC, has integrated the efforts of 50 scientists from research groups of 12 institutions, two of them from outside Spain, that cover a broad range of disciplines, including bioinformatics, genomics, oncology, evolution and conservation. The scientists have managed to read and organize 2.4 billion letters of DNA from Candiles, a male lynx born in the Sierra Morena lynx population, who now forms part of a program for breeding in captivity. To do so, they have used new sequencing techniques and developed innovative procedures to generate a high-quality draft genome on a limited budget. A total of 21,257 genes were identified, a number similar to that of human beings and other mammals, and they have been compared to those of cats, tigers, cheetahs and dogs. Specifically, Toni Gabaldón's group at the Centre for Genomic Regulation in Barcelona has compared the Iberian lynx genome with those of other species, attempting to identify genes that have lost their function because they have remained isolated and the existence of a small population of specimens of this species. Researchers have found evidence of modifications in genes related with the senses of hearing, sight and smell to facilitate the adaptation of the lynx to its environment, which have enabled them to become exceptional hunters specialized in rabbits as prey. History and diversity of the Iberian lynx With the aim of studying the history and genetic diversity of the species, analysis was conducted on the genomes of another ten Iberian lynxes from Doñana and Sierra Morena, the only two surviving populations on the Iberian Peninsula, which have been isolated from each other for decades. Researchers have also completed a comparative analysis with a European lynx, to discover the bonds between the two lynxes that inhabit Eurasia. The Iberian lynx began to diverge from its sister species, the Eurasian lynx (Lynx lynx) some 300,000 years ago, and the two species became completely separated some 2,500 years ago. Throughout that period, they continued to cross-breed and exchange genes, probably in the periods between glaciations, when the climatology allowed the species to spread and encounter each other on the Iberian Peninsula and in southern Europe. The demographic history of the Iberian lynx has been marked by three historic declines, the last of which took place some 300 years ago, decimating its population. In addition to this, there was a drastic drop in the number of specimens in the 20th century due to its persecution, the destruction of its habitat, and two major viral epidemics suffered by the rabbit, its main food source. Scientists have interpreted these demographic drops as the cause of the low levels of diversity observed, and warn that this could impair the lynx's capacity to adapt to changes in its environment (climate, disease, etc.). Furthermore, existence of multiple potentially harmful genetic variants has been confirmed, which could be contributing to the reduced survival and reproduction rates of the species. This genetic deterioration is especially marked in the Doñana population-smaller, and isolated for a longer period-which has half the genetic diversity of the Sierra Morena group. Nevertheless, the study reflects the situation before the exchange between the two relict populations and their inter-breeding in captivity were begun. These measures, taken within the Iberian lynx conservation program, have led to improvement of the species' genetic situation in recent years. The use of new genomic resources, within the framework of the project, will contribute to optimizing management aimed at preserving the greatest genetic diversity, in addition to diminishing these populations' genetic defects as much as possible. In addition to Doñana Biological Station (EBD-CSIC), also taking part in the project were the National Center for Genomic Analysis (CNAG-CRG); the Centre for Genomic Regulation (CRG); the Spanish National Cancer Research Center (CNIO); the Evolutionary Genomics Group of the Hospital del Mar Medical Research Institute (IMIM); the Institute of Evolutionary Biology (IBE, CSIC-UPF); the University Institute of Oncology of Asturias (IUOPA); the Institut de Biotecnologia i de Biomedicina and the Unit of Cell Culture of the Autonomous University of Barcelona (UAB); the Biological Research Center (CIB-CSIC) and the Catalan Institution for Research and Advanced Studies (ICREA). Furthermore, the project has received the cooperation of a team from College of Veterinary Medicine of Texas A&M University and the Bioinformatics Research Center of the University of Aarhus (Denmark).

News Article | December 14, 2016
Site: www.sciencenews.org

No paper or digital trails document ancient humans’ journey out of Africa to points around the globe. Fortunately, those intrepid travelers left a DNA trail. Genetic studies released in 2016 put a new molecular spin on humans’ long-ago migrations. These investigations also underscore the long trek ahead for scientists trying to reconstruct Stone Age road trips. “I’m beginning to suspect that the ancient out-of-Africa process was complex, involving several migrations and subsequent extinctions,” says evolutionary geneticist Carles Lalueza-Fox of the Institute of Evolutionary Biology in Barcelona. Untangling those comings, goings and dead ends increasingly looks like a collaborative job for related lines of evolutionary research — comparisons of DNA differences across populations of present-day people, DNA samples retrieved from the bones of ancient hominids, archaeological evidence, fossil finds and studies of ancient climates. It’s still hard to say when the clouds will part and a clear picture of humankind’s journey out of Africa will appear. Consider four papers published in October that featured intriguing and sometimes contradictory results. Three new studies expanded the list of present-day populations whose DNA has been analyzed. The results suggest that most non-Africans have inherited genes from people who left Africa in a single pulse between about 75,000 and 50,000 years ago (SN: 10/15/16, p. 6). One team, studying DNA from 142 distinct human populations, proposed that African migrants interbred with Neandertals in the Middle East before splitting into groups that headed into Europe or Asia. Other scientists whose dataset included 148 populations concluded that a big move out of Africa during that time period erased most genetic traces of a smaller exodus around 120,000 years ago. A third paper found that aboriginal Australians and New Guinea’s native Papuans descend from a distinctive mix of Eurasian populations that, like ancestors of other living non-Africans, trace back to Africans who left their homeland around 72,000 years ago. The timing of those migrations may be off, however. A fourth study, based on climate and sea level data, identified the period from 72,000 to 60,000 years ago as a time when deserts largely blocked travel out of Africa. Computer models suggested several favorable periods for intercontinental travel, including one starting around 59,000 years ago. But archaeological finds suggest that humans had already spread across Asia by that time. Clashing estimates of when ancient people left Africa should come as no surprise. To gauge the timing of these migrations, scientists have to choose a rate at which changes in DNA accumulate over time. Evolutionary geneticist Swapan Mallick of Harvard Medical School and the other authors of one of the new genetics papers say that the actual mutation rate could be 30 percent higher or lower than the mutation rate they used. Undetermined levels of interbreeding with now-extinct hominid species other than Neandertals may also complicate efforts to retrace humankind’s genetic history (SN: 10/15/16, p. 22), as would mating between Africans and populations that made return trips. “This can be clarified, to some extent, with genetic data from ancient people involved in out-of-Africa migrations,” says Lalueza-Fox. So far, though, no such data exist. The uncertainty highlights the need for more archaeological evidence. Though sites exist in Africa and Europe dating from more than 100,000 years ago to 10,000 years ago, little is known about human excursions into the Arabian Peninsula and the rest of Asia. Uncovering more bones, tools and cultural objects will help fill in the picture of how humans traveled, and what key evolutionary transitions occurred along the way. Mallick’s team has suggested, for example, that symbolic and ritual behavior mushroomed around 50,000 years ago, in the later part of the Stone Age, due to cultural changes rather than genetic changes. Some archaeologists have proposed that genetic changes must have enabled the flourishing of personal ornaments and artifacts that might have been used in rituals. But comparisons of present-day human DNA to that of Neandertals and extinct Asian hominids called Denisovans don’t support that idea. Instead, another camp argues, humans may have been capable of these behaviors some 200,000 years ago. Nicholas Conard, an archaeologist at the University of Tübingen in Germany, approaches the findings cautiously. “I do not assume that interpretations of the genetic data are right,” he says. Such reconstructions have been revised and corrected many times over the last couple of decades, which is how “a healthy scientific field moves forward,” Conard adds. Collaborations connecting DNA findings to archaeological discoveries are most likely to produce unexpected insights into where we come from and who we are.

Stone G.N.,Institute of Evolutionary Biology | Nee S.,Institute of Evolutionary Biology | Felsenstein J.,University of Washington
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

How do we quantify patterns (such as responses to local selection) sampled across multiple populations within a single species? Key to this question is the extent to which populations within species represent statistically independent data points in our analysis. Comparative analyses across species and higher taxa have long recognized the need to control for the non-independence of species data that arises through patterns of shared common ancestry among them (phylogenetic non-independence), as have quantitative genetic studies of individuals linked by a pedigree. Analyses across populations lacking pedigree information fall in the middle, and not only have to deal with shared common ancestry, but also the impact of exchange of migrants between populations (gene flow). As a result, phenotypes measured in one population are influenced by processes acting on others, and may not be a good guide to either the strength or direction of local selection. Although many studies examine patterns across populations within species, few consider such non-independence. Here, we discuss the sources of non-independence in comparative analysis, and show why the phylogeny-based approaches widely used in cross-species analyses are unlikely to be useful in analyses across populations within species. We outline the approaches (intraspecific contrasts, generalized least squares, generalized linear mixed models and autoregression) that have been used in this context, and explain their specific assumptions. We highlight the power of 'mixed models' in many contexts where problems of non-independence arise, and show that these allow incorporation of both shared common ancestry and gene flow. We suggest what can be done when ideal solutions are inaccessible, highlight the need for incorporation of a wider range of population models in intraspecific comparative methods and call for simulation studies of the error rates associated with alternative approaches. © 2011 The Royal Society.

News Article | March 14, 2016
Site: www.sciencenews.org

Neandertals hung out in what’s now northern Spain around 430,000 years ago, an analysis of ancient DNA suggests. That’s an earlier Neandertal presence in Europe, by at least 30,000 years, than many researchers had assumed. Fragments of nuclear DNA from a tooth and partial leg bone discovered at Sima de los Huesos, a chamber deep inside a Spanish cave, resemble corresponding parts of a previously reassembled Neandertal genome, researchers say in a study published online March 14 in Nature. Not much nuclear DNA survives in such ancient fossils, say paleogeneticist Matthias Meyer of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and his colleagues. Meyer’s group recovered DNA fragments covering a fraction of 1 percent of the newly recovered Neandertal tooth and leg genomes. Just enough DNA remained to enable comparisons with DNA of a Neandertal woman (SN: 1/25/14, p. 17) and a Denisovan woman (SN: 9/22/12, p. 5). Denisovans are considered close genetic cousins of Neandertals. The early age for the new genetic finds challenges the idea that fossils from Sima de los Huesos, or pit of bones, come from a species called Homo heidelbergensis. Some researchers have suspected that by around 400,000 years ago, H. heidelbergensis gave rise to evolutionary precursors of both Neandertals and Homo sapiens. An ancient genetic puzzle has also emerged at Sima de los Huesos. On one hand, nuclear DNA — which passes from both parents to their children — pegs the Spanish hominids as Neandertals. But mitochondrial DNA — typically inherited only from the mother — already extracted from one Sima de los Huesos fossil (SN: 12/28/13, p. 8) and described for a second fossil in the new study has more in common with Denisovans. Denisovans lived in East Asia at least 44,000 years ago, but their evolutionary history is unknown. If early Neandertals lived in northern Spain roughly 430,000 years ago, “we have to go back further in time to reach the common ancestor of Neandertals and Denisovans,” Meyer says. The new genetic data from Sima de los Huesos now suggest that Denisovans split from Neandertals perhaps 450,000 years ago, says paleoanthropologist Chris Stringer of the Natural History Museum in London. Genetic and fossil evidence point to Neandertals and H. sapiens diverging from a common ancestor around 650,000 years ago, he proposes. But it’s hard to say whether that common ancestor was H. heidelbergensis, Stringer adds. “Research must refocus on fossils from 400,000 to 800,000 years ago to determine which ones might lie on ancestral lineages of Neandertals, Denisovans and modern humans.” Hominids throughout Eurasia during that time may have shared a mitochondrial DNA pattern observed in Sima de los Huesos Neandertals and Asian Denisovans, Meyer suggests. If that was the case, Neandertals acquired a new form of mitochondrial DNA by interbreeding with modern humans or their direct ancestors from Africa sometime between 430,000 and 100,000 years ago (SN: 3/19/16, p. 6). Another possibility is that Neandertals traveled to Europe from Asia more than 430,000 years ago, carrying Denisovan mitochondrial DNA with them, says paleogeneticist Carles Lalueza-Fox of the Institute of Evolutionary Biology in Barcelona. Or hybrid descendants of early Neandertals and early Denisovans may have lived at Sima de los Huesos, carrying Denisovan mitochondrial DNA, he speculates. “We really need more genetic data from Sima de los Huesos, and other sites of that age, to narrow down these scenarios,” Meyer says.

Davey J.L.,Institute of Evolutionary Biology | Blaxter M.W.,University of Edinburgh
Briefings in Functional Genomics | Year: 2010

Next-generation sequencing technologies are making a substantial impact on many areas of biology, including the analysis of genetic diversity in populations. However, genome-scale population genetic studies have been accessible only to well-funded model systems. Restriction-site associated DNA sequencing, a method that samples at reduced complexity across target genomes, promises to deliver high resolution population genomic dataçthousands of sequenced markers across many individuals-for any organism at reasonable costs. It has found application in wild populations and non-traditional study species, and promises to become an important technology for ecological population genomics. © The Author 2011. Published by Oxford University Press. All rights reserved.

Harrison R.J.,Institute of Evolutionary Biology | Charlesworth B.,Institute of Evolutionary Biology
Molecular Biology and Evolution | Year: 2011

Patterns of synonymous codon usage vary between organisms and are controlled by neutral processes (such as drift and mutation) as well as by selection. Here we show that an additional neutral process, GC-biased gene conversion (gBGC), plays a part in shaping patterns of both synonymous codon usage and amino acid composition in a manner dependent upon the local recombination rate. We obtain estimates of the strength of gBGC acting on synonymous sites in five species of yeast, which we find to be a much weaker force than selection. We use this to correct estimates of the strength of selection on codon usage bias, which are normally confounded by the action of gBGC. Our estimate of the rate of gBGC agrees well with an experimentally determined value obtained from Saccharomyces cerevisiae. We also find that, contrary to expectation, codon usage bias is highest in areas of intermediate levels of recombination for GC-ending optimal codons. Possible reasons for this are discussed. © 2010 The Author.

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