Inbreeding and population/demographic shifts could have led to Neanderthal extinction

By: Thomas Schmitt Attorney on November 27, 2019 / comment : 0 Anthropology, Early Humans, Europe, Genetics, Near East, Ticker

Small populations, inbreeding, and random demographic fluctuations could have been enough to cause Neanderthal extinction, according to a study published in the open-access journal PLOS ONE by Krist Vaesen from Eindhoven University of Technology, the Netherlands, and colleagues.

Small populations, inbreeding, and random demographic fluctuations could have been enough to cause Neanderthal extinction, according to a new study [Credit: Petr Kratochvil (CC0)]

Paleoanthropologists agree that Neanderthals disappeared around 40,000 years ago--about the same time that anatomically modern humans began migrating into the Near East and Europe. However, the role modern humans played in Neanderthal extinction is disputed. In this study, the authors used population modelling to explore whether Neanderthal populations could have vanished without external factors such as competition from modern humans.

Using data from extant hunter-gatherer populations as parameters, the authors developed population models for simulated Neanderthal populations of various initial sizes (50, 100, 500, 1,000, or 5,000 individuals). They then simulated for their model populations the effects of inbreeding, Allee effects (where reduced population size negatively impacts individuals' fitness), and annual random demographic fluctuations in births, deaths, and the sex ratio, to see if these factors could bring about an extinction event over a 10,000-year period.

The population models show that inbreeding alone was unlikely to have led to extinction (this only occurred in the smallest model population). However, reproduction-related Allee effects where 25 percent or fewer Neanderthal females gave birth within a given year (as is common in extant hunter-gatherers) could have caused extinction in populations of up to 1,000 individuals. In conjunction with demographic fluctuations, Allee effects plus inbreeding could have caused extinction across all population sizes modelled within the 10,000 years allotted.

The population models are limited by their parameters, which are based on modern human hunter-gatherers and exclude the impact of the Allee effect on survival rates. It's also possible that modern humans could have impacted Neanderthal populations in ways which reinforced inbreeding and Allee effects, but are not reflected in the models.

However, by showing demographic issues alone could have led to Neanderthal extinction, the authors note these models may serve as a "null hypothesis" for future competing theories--including the impact of modern humans on Neanderthals.

The authors add: "Did Neanderthals disappear because of us? No, this study suggests. The species' demise might have been due merely to a stroke of bad, demographic luck."

Source: Public Library of Science [November 27, 2019]

Unique sled dogs helped the inuit thrive in the North American Arctic

By: Thomas Schmitt Attorney on November 27, 2019 / comment : 0 Archaeology, Arctic, Genetics, Indigenous Cultures, North America, Ticker

A unique group of dogs helped the Inuit conquer the tough terrain of the North American Arctic, major new analysis of the remains of hundreds of animals shows.

A team of Greenland sled dogs working in Greenland’s Disko Bay  [Credit: Tatiana Feuerborn]

The study shows that the Inuit brought specialised dogs with them when they migrated from Alaska and Siberia instead of adopting local dogs they would have come across during their migration. They instead maintained their own dogs, suggesting they were keen to enhance or keep the special features they had. By analysing the shape of elements from 391 dogs, the study shows that the Inuit had larger dogs with a proportionally narrower cranium to these earlier dogs. The Inuit dogs are the direct ancestors of modern Arctic sledge dogs, although their appearance has continued to change over time.

Experts had thought the Inuit used dogs to pull sledges, and this is the first study which shows they introduced a new dog population to the region to do this. These dogs then spread across the North American Arctic alongside Inuit migrants.

Dr Carly Ameen, an archaeologist from the University of Exeter who led the study, said: "Dogs have lived in North America for as long as humans, but we show here that the Inuit brought new dogs to the region which were genetically distinct and physically different from earlier dogs.

"Thousands of years ago there was not the huge number of dog breeds as we know them today. Through analysing the DNA and morphology of the remains of hundreds of dogs we've found that the dogs used by the Inuit had distinctive skull and teeth shapes, and would have likely looked different in life to dogs already in the Arctic."

The ancestors of these dogs arrived with the Inuit to the North American Arctic [Credit: Tatiana Feuerborn]

Experts also examined the DNA from 921 dogs and wolves who lived during the last 4,500 years. This analysis of the DNA, and the locations and time periods in which they were found, shows dogs from Inuit sites occupied from around 2,000 years ago were genetically different from the dogs already in the region.

Study co-lead author Tatiana Feuerborn, from the Globe Institute in Denmark and the Centre for Palaeogenetics in Sweden, said: "Archaeological evidence has shown us that before the Inuit arrived in North America dog sledging was a rarity. Our analysis of the DNA suggests dogs brought by the Inuit were distinct from the earlier dogs of the North American Arctic to fill specialist role in helping communities thrive in this hostile environment by aiding with transportation and hunting. The genetic legacy of these Inuit dogs can still be seen today in Arctic sledge dogs."

The Inuit were specialised sea mammal hunters, and were more mobile than other groups living in the Arctic, migrating huge distances across the region over 1,000 years ago, with the help of dog sledges and water craft. Today, sledge dogs whose origins can be traced back to the Inuit period continue to be an important part of Arctic communities.

The article is published in the journal Proceedings of the Royal Society B.

Source: University of Exeter [November 27, 2019]

Researchers show how feathers propel birds through air and history

By: Thomas Schmitt Attorney on November 27, 2019 / comment : 0 Biology, Early Birds, Evolution, Fossils, Genetics

New research from an international team led by USC scientists set out to learn how feathers developed and helped birds spread across the world. Flight feathers, in particular, are masterpieces of propulsion and adaptation, helping penguins swim, eagles soar and hummingbirds hover.

A Taiwan blue magpie in flight [Credit: Shao Huan Lang]

Despite such diversity, the feather shares a common core design: a one-style-fits-all model with option trims for specialized performance. This simplicity and flexibility found in nature holds promise for engineers looking for better ways to build drones, wind turbines, medical implants and other advanced materials.

Those findings, published in Cell, offer an in-depth look at the form and function of a feather based on a comparative analysis of their physical structure, cellular composition and evolution. The study compares feathers of 21 bird species from around the world.

"We've always wondered how birds can fly in so many different ways, and we found the difference in flight styles is largely due to the characteristics of their flight feathers," said Cheng-Ming Chuong, the study's lead author and a developmental biologist in the Department of Pathology at the Keck School of Medicine of USC. "We want to learn how flight feathers are made so we can better understand nature and learn how biological architecture principles can benefit modern technology."

To gain a comprehensive understanding of the flight feather, Chuong formed a multi-disciplinary international team with Wen Tau Juan, a biophysicist at the Integrative Stem Cell Center, China Medical University in Taiwan. The work involved experts in stem cells, molecular biology, anatomy, physics, bio-imaging, engineering, materials science, bioinformatics and animal science. The bird species studied include ostrich, sparrow, eagle, chickens, ducks, swallow, owl, penguin, peacock, heron and hummingbird, among others.

They compared feathers using fossils, stem cells and flight performance characteristics. They focused on the feather shaft, or rachis, that supports the feather much like a mast holds a sail, bearing the stress between wind and wing. They also focused on the vane, the lateral branches astride the shaft that give the feather its shape to flap the air. And they examined how evolution shaped the barbs, ridges and hooks that help a feather hold its form and lock with adjacent feathers like Velcro to form a wing. The goal was to understand how a simple filament appendage on dinosaurs transformed into a three-level branched structure with different functions.

For birds such as ducks, eagles and sparrows that fly in different modes, the scientists noted significant differences in the feather shaft compared to ground-hugging birds. On the rigid exterior, the shaft cortex was thinner and lightweight, while the interior was filled with porous cells resembling bubble wrap, aligned into bands of various orientations and reinforced with ridges that operate like tiny lateral beams. Together, it forms a light, hollow and buoyant structure to enable flight. Cross-sections of feather shafts of different birds show highly specialized shapes and orientations of the inner core and outer cortex.

This picture shows a the asymmetric vane and tapering main shaft of a single flight feather from a goshawk [Credit: Hao Howard Wu & Wen Tau Juan]

"The flight feather is made of two highly adaptable architectural modules, light and strong materials that can develop into highly adaptable configurations," Chuong said.

The researchers discovered two different molecular mechanisms guiding feather growth. Cortex thickness was governed by bone morphogenetic proteins, which are molecular signals for tissue growth. The porous feather interior, or medulla, relied upon a different mechanism known as transforming growth factor beta (TGF-b). Both components originate as stem cells in the bird's skin.

By contrast, feathers in flightless birds were simpler, consisting of a dense cortex exterior that is more rigid and sturdy with fewer internal struts and cells found in flying birds. The features were especially pronounced for penguins, which use wings as paddles under the water.

As part of the study, the researchers looked at nearly 100 million-year-old feathers, found embedded in amber in Myanmar. These fossils show early feathers lacked one key feature that modern birds have. Specifically, the researchers report how fossil feathers had barb branches and barbules, which form a feather vane by overlapping, but not hooklets. The hooklets, which act like clasps to turn fluffy feathers into a tight flat plane for high-performance flight, evolved later. The scientists also identified WNT2B, another growth factor, as the agent that controls hooklet formation. These also originated from epidermal stem cells.

Taken together, the findings show how feathered dinosaurs and early birds could form a primitive vane by overlapping barbule plates, although that wasn't aerodynamically fit to carry much load. As more complex composite features occurred in the wing, it got heavier, so feather shafts became stronger yet more lightweight, which led to stiffer feathers and sturdy wings that powered flight to carry birds around the world.

"Our findings suggest the evolutionary trends of feather shaft and vane are balanced for the best flight performance of an individual bird and become part of the selective basis of speciation," the study says. "The principles of functional architectures we studied here may also stimulate bio-inspired designs and fabrication of future composite materials for architectures of different scales, including wind turbines, artificial tissues, flying drones."

Source: University of Southern California [November 27, 2019]

Did human hunting activities alone drive great auks' extinction?

By: Thomas Schmitt Attorney on November 26, 2019 / comment : 0 Early Birds, Fossils, Genetics, Iceland, North America, Palaeontology, Scotland

New insight on the extinction history of a flightless seabird that vanished from the shores of the North Atlantic during the 19th century has been published in eLife.

A mounted great auk skin, The Brussels Auk (RBINS 5355), from the collections at the Royal Belgian Institute of Natural Sciences (RBINS) [Credit: Thierry Hubin, RBINS]

The findings suggest that intense hunting by humans could have caused the rapid extinction of the great auk, showing how even species that exist in large and widespread populations can be vulnerable to exploitation.

Great auks were large, flightless diving birds thought to have existed in the millions. They were distributed around the North Atlantic, with breeding colonies along the east coast of North America and especially on the islands off Newfoundland. They could also be found on islands off the coasts of Iceland and Scotland, as well as throughout Scandinavia.

But these birds had a long history of being hunted by humans. They were poached for their meat and eggs during prehistoric times, and this activity was further intensified in 1500 AD by European seamen visiting the fishing grounds of Newfoundland. Their feathers later became highly sought after in the 1700s, contributing further to their demise.

"Despite the well-documented history of exploitation since the 16th century, it is unclear whether hunting alone could have been responsible for the species' extinction, or whether the birds were already in decline due to natural environmental changes," says lead author Jessica Thomas, who completed the work as part of her PhD studies at Bangor University, UK, and the University of Copenhagen, Denmark, and is now a postdoctoral researcher at Swansea University, Wales, UK.

Great auk humeri from Funk Island. These samples are part of the great auk collection at the American Museum of Natural History [Credit: J. Thomas]

To investigate this further, Thomas and her collaborators carried out combined analyses of ancient genetic data, GPS-based ocean current data, and population viability - a process that looks at the probability of a population going extinct within a given number of years. They sequenced complete mitochondrial genomes of 41 individuals from across the species' geographic range and used their analyses to reconstruct the birds' population structure and dynamics throughout the Holocene period, the last 11,700 years of Earth's history.

"Taken together, our data don't suggest that great auks were at risk of extinction prior to intensive human hunting behaviour in the early 16th century," explains co-senior author Thomas Gilbert, Professor of Evolutionary Genomics at the University of Copenhagen. "But critically, this doesn't mean that we've provided solid evidence that humans alone were the cause of great auk extinction. What we have demonstrated is that human hunting pressure was likely to have caused extinction even if the birds weren't already under threat from environmental changes."

Gilbert adds that their conclusions are limited by a couple of factors. The mitochondrial genome represents only a single genetic marker and, due to limited sample preservation and availability, the study sample size of 41 is relatively small for population genetic analyses.

"Despite these limitations, the findings help reveal how industrial-scale commercial exploitation of natural resources have the potential to drive an abundant, wide-ranging and genetically diverse species to extinction within a short period of time," says collaborator Gary Carvalho, Professor in Zoology (Molecular Ecology) at Bangor University. This echoes the conclusions of a previous study* on the passenger pigeon, a bird that existed in significant numbers before going extinct in the early 20th century.

"Our work also emphasises the need to thoroughly monitor commercially harvested species, particularly in poorly researched environments such as our oceans," concludes co-senior author Michael Knapp, Senior Lecturer in Biological Anthropology and Rutherford Discovery Fellow at the University of Otago, New Zealand. "This will help lay the platform for sustainable ecosystems and ensure more effective conservation efforts."

Source: eLife [November 26, 2019]

Aquatic microorganisms offer important window on the history of life

By: Thomas Schmitt Attorney on November 25, 2019 / comment : 0 Biology, Evolution, Fossils, Genetics

The air, earth and water of our planet are pulsating with living things. Yet, a vast and diverse web of life exists, about which almost nothing is known. This is the world of flagellates, tiny organisms that persist in staggering numbers in many diverse ecosystems around the world.

The graphic shows a tree of life for complex forms known as Eukaryotes, that arose mysteriously around 1.2-2 billions years ago from a progenitor known as LECA (for Last Eukaryote Common Ancestor.) Jeremy Wideman and his colleagues used a new method to sequence mitochondrial DNA for around 100 species of flagellates--tiny aquatic organisms that populate many branches of the tree. These are seen on the graphic as red dots marking the particular lineages these flagellates belong to [Credit: Shireen Dooling]

According to Jeremy Wideman, a researcher at the Biodesign Center for Mechanisms in Evolution at Arizona State University, we have a great deal to learn from these delicate and wildly varied creatures. Among other surprises, flagellates could provide valuable clues about a shadowy event that may have occurred 1.5-2 billion years ago, (no one is really sure of the timing), with the arrival of a new type of cell.

Known as LECA, it was a sort of primal egg out of which the astonishing profusion of complex life--from flagellate organisms, fungi and plants, to insects, zebra, and humans, exploded and spread over the earth.

In new research published in the journal Nature Microbiology, Wideman and his colleagues, including Prof. Thomas Richards at the University of Exeter describe a new method for investigating the genomes of eukaryotic flagellate organisms, which have been notoriously tricky to pinpoint and sequence.

Specifically, they explored samples of mitochondrial DNA, sequencing around 100 such genomes for previously undocumented flagellates. The new technique could help scientists like Wideman begin to fill in the largely blank region of the eukaryotic puzzle, where flagellate life flourishes.

Cellular worlds

Wideman, originally a traditional cell biologist, became frustrated with the many unaddressed questions in the field, recently joining the emerging discipline of evolutionary cell biology. This rapidly advancing research area uses cells as fundamental units for the study of evolutionary processes and imports concepts from evolutionary biology to better understand how cells work. "I'm literally a cell biologist that wants to know more about things we know nothing about," he says.

Evolutionary cell biology is a profoundly transdisciplinary endeavor, fusing evolutionary theory, genomics and cell biology with quantitative branches of biochemistry, biophysics, and population genetics.

Flagellates include many parasites implicated in human disease, from the intestinal bug Giardia to more damaging trypanosomes, and leishmania. Flagellates also perform more benevolent tasks. As the major consumers of bacteria and other protists in aquatic ecosystems, they help ensure the recycling of limiting nutrients.

Single-celled eukaryotic organisms, which include flagellates, constitute the overwhelming majority of eukaryotic diversity, vastly outpacing the more familiar multicellular plants, animals, and fungi. Despite their importance and ubiquity across the globe, flagellates are, as Wideman stresses, an almost entirely unknown inhabitant of the living world and one of the most enigmatic. When viewed under a microscope, their often science fiction-like appearance is markedly distinct from the kinds of eukaryotic cells commonly described in biology textbooks. Their emergence from comparatively rudimentary prokaryotes marks the most momentous transition in the history of life on earth.

"Novel lineages of heterotrophic flagellates are being discovered at an alarming, rate," Wideman says. "In the last two years 2 kingdom level lineages have been discovered (see here and here), meaning lineages that have been evolving independently of animals and fungi for over a billion years." Nevertheless, researchers have barely scratched the surface of this astonishing diversity and new methods must be brought to bear to speed up the quest. (Heterotrophs are organisms that cannot synthesize their own food, relying instead on other organisms for nutrition.)

Microbial safari

Any drop of pond, lake or ocean water is likely to contain many flagellates, but separating them from a multitude of non-flagellates and accurately reading their genomes by conventional means has been slow and painstaking work. Only a minute fraction of extant flagellates have known genomic sequences and it's even possible that the overwhelming majority have never actually been seen. According to Wideman, flagellate life forms represent the 'dark matter' of the eukaryotic universe.

"Heterotrophic flagellates are the target," Wideman says. "They're not a lineage. They're many, many lineages that are from all over the tree of life. LECA, the Last Eukaryotic Common Ancestor, was a heterotrophic flagellate, which means, that every major lineage (of eukaryotes) evolved from some sort of heterotrophic flagellate."

To access the elusive flagellate mitochondrial DNA, the researchers exploited a feature common to all flagellates and from which they take their name--the existence of flagella, which, unlike in animal sperm are on the front of cells and are often used to pull them forward like a microscopic breast stroke but are also involved in sensation, feeding, and perhaps other, as-yet unknown functions.

Flagella are rich in a particular protein known as tubulin. The new method for identifying flagellates and distinguishing them from their aquatic neighbors--primarily algae and bacteria--capitalizes on this fact by applying a selective stain to flagella-bearing organisms, activated by their high tubulin content. (Algal cells are naturally marked by their chloroplasts, which the flagellates of interest in the new study lack.)

Samples of sea water collected in 2014 off the coast of California provided a test case. Using the technique, the researchers gathered a windfall of mitochondrial sequence data, significantly expanding the catalog of flagellates identified by molecular means. Indeed, they doubled the existing mitochondrial DNA library for flagellate organisms. "We got many, many different kinds of organisms. So it was a very rich sample and very few were identical," Wideman says.

In search of LECA

Apart from the mystery of life's origin, the puzzle of where eukaryotes came from and how the LECA event transpired is the most important and vexing unanswered question in all of biology. (It has been dubbed the black hole at the heart of the living world.)

Correctly establishing the sequence of events underlying the crucial innovations within eukaryotes, from whence all complex life sprang, will take much more research in unexplored regions of the existing eukaryotic domain, particularly, the flagellates. Wideman believes the rapid advance of techniques for identifying and sequencing these organisms, such as the one outlined in the new study, offer hope such questions may one day find answers.

Author: Richard Harth | Source: Arizona State University [November 25, 2019]

Unravelling gene expression

By: Thomas Schmitt Attorney on November 21, 2019 / comment : 0 Biology, Evolution, Genetics

The DNA of a single cell is 2-3 meters long end-to-end. To fit and function, DNA is packaged around specialized proteins. These DNA-protein complexes are called nucleosomes, and they are a small part of a larger structure called chromatin. Nucleosomes can be thought of as the cell's DNA storage and protection unit.

The pioneer transcription factor Rap1 pries open compact chromatin structure to activate genes [Credit: Beat Fierz, EPFL]

When a particular gene needs to be expressed, the cell requires access to the protected DNA within chromatin. This means that the chromatin structure must be opened and the nucleosomes must be removed to expose the underlying target gene.

This takes place in the orchestrated process of "chromatin remodeling", which regulates gene expression and involves a multitude of actors. Unravelling this pivotal step not only furthers our fundamental understanding, but may also help in the development of genetic engineering tools.

Now the lab of Beat Fierz at EPFL, has been able to uncover the first steps in the chromatin-opening process at the level of a single molecule, using a combination of chemical biology and biophysical methods. Published in Molecular Cell, the work looks at the role of a group of proteins called "pioneer transcription factors". These proteins bind to specific DNA regions within chromatin that are themselves shielded from other proteins. Little is known about how these factors overcome the barriers of the chromatin maze.

The graphical abstract of the paper, showing the way Rap1 accesses chromatin [Credit: M. Mivelaz et al. 2019]

Fierz's lab looked at yeast, which is a model organism for human genetics. The method involved replicating the architecture of yeast genes, combined with single-molecule fluorescence. The researchers studied a yeast pioneer transcription factor called Rap1, and found that it choreographs chromatin remodeling, allowing access to other proteins required for gene expression that were previously obstructed.

To do this, Rap1 first binds chromatin and then influences the action of a large molecular machine called "Remodeling the Structure of Chromatin" (RSC), displacing nucleosomes and paving the way to the now-exposed DNA for other proteins involved in controlling gene expression.

By revealing the physico-chemical mechanism of how Rap1 gains access to chromatin and opens it up, the EPFL study proposes a biological model for other pioneer transcription factors, but also provides the tools for investigating them at the level of a single molecule.

Source: Ecole Polytechnique Federale de Lausanne [November 21, 2019]

Self-restrained genes enable evolutionary novelty

By: Thomas Schmitt Attorney on November 21, 2019 / comment : 0 Biology, Evolution, Genetics

Changes in the genes that control development can potentially make large contributions to evolution by generating new morphologies in plants and animals. However, because developmental genes frequently influence many different processes, changes to their expression carry a risk of "collateral damage". Scientists at the Max Planck Institute for Plant Breeding Research in Cologne, and collaborators, have now shown how gene self-repression can reduce the potential side effects of novel gene expression so that new forms can evolve. This self-regulation occurs via a distinctive molecular mechanism employing small regions of genomic DNA called low-affinity transcription factor binding sites.

A confocal micrograph of a young leaf of Cardamine hirsuta (hairy bittercress) with emerging leaflets, showing distribution of the RCO protein. Cell outlines are shown in gray. RCO shown here in red colour is active at the base of initiating leaflets where it reduces  growth, leading to the formation of leaflets that are separated from each other  [Credit: Neha Bhatia and Peter Huijser]

Suppose a bird develops a modified wing shape, which makes flying easier and could be beneficial to its survival. If this gene change also altered the bird's color, making it less attractive to mates, then the advantageous wing-shape modification would be unlikely to persist. So, how then does nature balance the potential for novelty, with the risk of side effects that may prevent novelty from arising? Using the evolution of leaf shape as an example, an international team led by Director Miltos Tsiantis has provided fresh insight into this question.

This new study was done in the hairy bittercress, a small weed that the Tsiantis group has developed into a model system for understanding evolution of plant form. It builds on previous work from the group in which a gene called RCO was found to have driven leaf shape diversification in mustard plants by acquiring a novel expression pattern.

RCO encodes a transcription factor, a type of protein that can turn other genes on or off, and RCO's new expression pattern resulted in the emergence of the more complex leaf shapes found in bittercress. The researchers have now shown that this change in gene expression was accompanied by RCO acquiring the ability to repress its own activity. Mike Levine, Director of the Lewis-Sigler Institute for Integrative Genomics at Princeton University who was not involved in the study, finds this particular insight "very compelling". As the self-repression of RCO "limits the scope of its activity", Levine explains, it "thereby blocks potentially deleterious influences on cell development and function".

Stimulating cytokinin

As a next step, the scientists identified the genes targeted by RCO, and found that many of them are responsible for coordinating local levels of cytokinin - a widely acting plant hormone known to affect cell growth. Importantly, when the self-regulation of RCO is modified, RCO stimulates cytokinin excessively and leaf shape is altered in ways that can negatively affect plant fitness. This finding confirms the idea that self-repression of RCO could be essential for the persistence of RCO-induced novel leaf morphologies.

What's particularly interesting is that this self-repression of RCO occurs in a very distinctive way. The scientists discovered that it is based on many weak interactions between the RCO protein and RCO regulatory DNA at low-affinity binding sites. "This finding is exciting", explains Tsiantis, "because low-affinity binding sites can evolve relatively quickly, thus offering an easy way for evolution to keep changes in gene expression in check, by lowering a regulator's expression".

Soft repression

Indeed, this latest work from Tsiantis's team directly demonstrates that low-affinity transcription factor binding sites can play a major role in the generation of morphological novelty. By providing a tool to "softly" repress RCO expression, these sites dampen the effects of RCO expression changes and allow cytokinin levels to be fine-tuned. This in turn promotes the appearance of more complex leaf shapes, e.g., by precisely regulating the outgrowth of lobes or leaflets along the margins of developing leaves.

These results will stimulate further efforts to understand the influence of low-affinity transcription factor binding sites on development, diversity and disease. For example, there is increasing awareness that changes in the regulation of developmental genes are a major contributor to human disease, and that other regulatory changes can reduce disease severity or protect individuals who carry disease variants. While the specific DNA sequences underlying these effects are often unknown, this latest work highlights low-affinity transcription factor binding sites as excellent candidate regions for identifying causal sequences of disease susceptibility, and for understanding variation in trait diversity more broadly in complex eukaryotes.

The study is published in Current Biology.

Source: Max Planck Society [November 21, 2019]

Researchers sequence genome of the 'devil worm'

By: Thomas Schmitt Attorney on November 21, 2019 / comment : 0 Biology, Evolution, Genetics

When scientists discovered a worm deep in an aquifer nearly one mile underground, they hailed it as the discovery of the deepest-living animal ever found. Now American University researchers, reporting in Nature Communications, have sequenced the genome of the unique animal, referred to as the 'Devil Worm' for its ability to survive in harsh, subsurface conditions. The Devil Worm's genome provides clues to how an organism adapts to lethal environmental conditions. Future research into how it evolved could help humans learn lessons for how to adapt to a warming climate.

H. Mephisto (the Devil Worm) (microscopic image, magnified 200x) [Credit: Prof. John Bracht, American University]

In 2008, Gaetan Borgonie from the University of Ghent and Princeton University geoscientist Tullis Onstott discovered the microscopic Devil Worm while investigating subterrestrial bacterial communities in active gold mines in South Africa. Borgonie and his team were stunned to discover the worm, a complex, multi-cellular animal thriving in an environment thought only livable for microbes, with high temperatures, little oxygen and high amounts of methane.

Researchers named the worm Halicephalobus mephisto, in honor of Mephistopheles, a subterranean demon from the medieval German legend Faust.

The Devil Worm is the first subterrestrial animal to have its genome sequenced. The genome offers evidence of how life can exist below Earth's surface and opens up a new way of understanding how life can survive beyond Earth, said John Bracht, assistant professor of biology at American University who led the genome sequencing project.

The sequencing revealed that the genome encodes an unusually large number of heat-shock proteins known as Hsp70, which is notable because many nematode species whose genomes are sequenced do not reveal such a large number. Hsp70 is a well-studied gene that exists in all life forms and restores cellular health due to heat damage.

Many of the Hsp70 genes in the Devil Worm's genome were copies of themselves. The genome also has extra copies of AIG1 genes, known cellular survival genes in plants and animals. More research will be needed, but Bracht believes the presence of copies of the gene signifies the worm's evolutionary adaptation.

"The Devil Worm can't run away; it's underground," Bracht explained. "It has no choice but to adapt or die. We propose that when an animal cannot escape intense heat, it starts making additional copies of these two genes to survive."

By scanning other genomes, Bracht identified other cases where the same two gene families, Hsp70 and AIG1, are expanded. The animals he identified are bivalves, a group of mollusks including clams, oysters and mussels. They are heat-adapted like the Devil Worm. This suggests that the pattern identified in the Devil Worm may extend more generally to organisms unable to escape environmental heat. This work was also recently published in the Journal of Molecular Evolution with an AU Biology undergraduate first author, Megan Guerin.

Bracht got the chance to sequence the unique worm's genome as a post-doctoral fellow at Princeton University. He carried the project over to American University when he joined the biology faculty in 2014. Two biology master's students working in his lab, Deborah Weinstein and Sarah Allen, contributed research and writing of the Nature Communications paper and are first and second authors, respectively, on the manuscript. Kathryn Walters-Conte, Ph.D., director of AU's Master's in Biotechnology program, also contributed to the paper.

Nearly a decade ago, the Devil Worm was unknown and living below the Earth's surface. Now it's a subject of study in science laboratories, including Bracht's. When Bracht brought Devil Worms from a laboratory in South Africa that cultures them to his laboratory at AU, he recalls saying to his students that aliens landed at AU. The metaphor isn't a stretch. NASA supports research of the Devil Worm for what it can teach scientists about the search for life beyond Earth.

"Part of this work entails looking for 'biosignatures' of life--stable chemical clues left behind by living things. We focus on a ubiquitous biosignature of organic life--genomic DNA--obtained from an animal that has adapted to an environment once considered uninhabitable to complex life: the deep terrestrial subsurface," Bracht said. "It is work that might prompt us to broaden the search for extraterrestrial life to 'uninhabitable' exoplanets' deep subterrestrial regions."

Nematodes are well suited to studies of evolutionary adaptation, Bracht said. They have adapted to a diverse set of environments and are among the most abundant animals on earth. Future work involving the Devil Worm in Bracht's lab will pinpoint Hsp70's function, such as inactivating the gene to test its response to heat stress. Other work could involve gene-transfer studies in C.elegans, a type of heat-intolerant microscopic roundworm, to see if it becomes heat-resilient.

Source: American University [November 21, 2019]