The arms race is between mobile DNA sequences known as “retrotransposons” (a.k.a. “jumping genes”) and the genes that have evolved to control them. The UC Santa Cruz researchers have, for the first time, identified genes in humans that make repressor proteins to shut down specific jumping genes. The researchers also traced the rapid evolution of the repressor genes in the primate lineage.
Their findings, published September 28 in Nature, show that over evolutionary time, primate genomes have undergone repeated episodes in which mutations in jumping genes allowed them to escape repression, which drove the evolution of new repressor genes, and so on. Furthermore, their findings suggest that repressor genes that originally evolved to shut down jumping genes have since come to play other regulatory roles in the genome.
“We have basically the same 20,000 protein-coding genes as a frog, yet our genome is much more complicated, with more layers of gene regulation. This study helps explain how that came about,” said Sofie Salama, a research associate at the UC Santa Cruz Genomics Institute who led the study.
Retrotransposons are thought to be remnants of ancient viruses that infected early animals and inserted their genes into the genome long before humans evolved. Now they can only replicate themselves within the genome. Depending on where a new copy gets inserted into the genome, a jumping event can disrupt normal genes and cause disease. Often the effect is neutral, simply adding to the overall size of the genome. Very rarely the effect might be advantageous, because the added DNA can itself be a source of new regulatory elements that enhance gene expression. But the high probability of deleterious effects means natural selection favors the evolution of mechanisms to prevent jumping events.
Scientists estimate that jumping genes or “transposable elements” account for at least 50 percent of the human genome, and retrotransposons are by far the most common type.
“There have been successive waves of retrotransposon activity in primate evolution, when a transposable element changed to become expressed and replicated itself throughout the genome until something turned it off,” Salama said. “We’ve discovered a major mechanism by which the genome is able to shut down these mobile DNA elements.”
The repressors identified in the new study belong to a large family of proteins known as “KRAB zinc finger proteins.” These are DNA-binding proteins that repress gene activity, and they constitute the largest family of gene-regulating proteins in mammals. The human genome has over 400 genes for KRAB zinc finger proteins, and about 170 of them have emerged since primates diverged from other mammals.
According to Salama, her team’s findings support the idea that expansion of this family of repressor genes occurred in response to waves of retrotransposon activity. Because repression of a jumping gene also affects genes located near it on the chromosome, the researchers suspect that these repressors have been co-opted for other gene-regulatory functions, and that those other functions have persisted and evolved long after the jumping genes the repressors originally turned off have degraded due to the accumulation of random mutations.
“The way this type of repressor works, part of it binds to a specific DNA sequence and part of it binds other proteins to recruit a whole complex of proteins that creates a repressive landscape in the genome. This affects other nearby genes, so now you have a potential new layer of regulation available for further evolution,” Salama said.
KRAB zinc finger proteins are the subject of intensive research as scientists try to sort out their many regulatory roles within the genome. The idea that they are involved in repression of jumping genes is not new–previous studies by other researchers have shown that these proteins silence jumping genes in mouse embryonic stem cells. But until now, no one had been able to demonstrate that the same thing occurs in human cells.
The UC Santa Cruz team developed a novel assay to test whether a particular KRAB zinc finger protein could shut down certain jumping genes. The first authors of the paper, postdoctoral researcher Frank Jacobs and graduate student David Greenberg, came up with the strategy of testing primate retrotransposons in non-primate cells by using mouse embryonic stem cells that contain a single human chromosome. In the environment of a mouse cell, jumping genes that were repressed in primate cells became active. Greenberg then developed an assay for testing individual zinc finger proteins for their ability to turn off a primate jumping gene in the mouse cell environment.
“We did all our tests in mouse cells because they lack all of the primate zinc finger proteins, so when you put primate retrotransposons into a mouse cell they’re all active,” Salama explained.
The results demonstrated that two human proteins called ZNF91 and ZNF93 bind and repress two major classes of retrotransposons (known as SVA and L1PA) that are currently or recently active in primates. Assistant research scientist Benedict Paten directed graduate student Ngan Nguyen in a painstaking analysis of primate genomes, including the reconstruction of ancestral genomes, which showed that ZNF91 underwent structural changes 8 to 12 million years ago that enabled it to repress SVA elements.
Experiments with ZNF 93, which shuts down L1PA retrotransposons, provided a striking illustration of the arms race between jumping genes and repressors. The researchers found that, while it is good at shutting down many L1PA elements, there is one subset of a recently evolved lineage of L1PA that has lost a short section of DNA that includes the ZNF93 binding site. Without the binding site, these jumping genes evade repression by ZNF93. Interestingly, when the researchers put the missing sequence back into one of these genes and put it in a mouse cell without ZNF93, they found that it was better at jumping. So even though the sequence helps with jumping activity, losing it gives the jumping gene an advantage in primates by allowing it to escape repression by ZNF93.
“That’s kind of the icing on the cake for aficionados of molecular evolution, because it demonstrates that this is a never-ending race,” Salama said. “KRAB zinc finger proteins are a rare class of proteins that is rapidly expanding and evolving in mammalian genomes, which makes sense because the transposable elements are themselves continually evolving to escape repression.”
Corresponding author David Haussler, professor of biomolecular engineering and director of the UC Santa Cruz Genomics Institute, said the study involved close collaboration between his group’s “wet lab,” directed by Salama, and the “dry lab” where researchers under Paten’s direction used the computational tools of genome bioinformatics to reconstruct the evolutionary history of primate genomes. Haussler, a Howard Hughes Medical Institute investigator who has used his background in computer science to do pioneering work in genomics, said he established the wet lab to enable just this kind of collaboration.
“Both parts were integral to this study, and there was a lot of back and forth between them. This paper shows how important it is to integrate computational and experimental approaches to fundamental scientific problems, such as how and why we continuously evolve to be more complex,” Haussler said.
Reference: Frank M. J. Jacobs, David Greenberg, Ngan Nguyen, Maximilian Haeussler, Adam D. Ewing, Sol Katzman, Benedict Paten, Sofie R. Salama, David Haussler. An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons. Nature, 2014; DOI: 10.1038/nature13760
In a new paper by cell biologist Magdalena Bezanilla of the University of Massachusetts Amherst, she and her doctoral student Shu-Zon Wu present a detailed new model that for the first time proposes how plant cells precisely position a “dynamic and complex” structure called a phragmoplast at the cell center during every division and how it directs cytokinesis. The work is reported in the current issue of the journal, eLife.
The complicated cytokinesis process begins at the cell center where the phragmoplast sends out tendrils toward opposite sides of the cell like a belt across its waist. These polymers, microtubules and actin filaments travel tens or hundreds of microns towards the cell wall to a predetermined position where a special structure called the cell plate will form. The new wall making two new cells will take shape along this pathway between the cell plates on opposite walls.
“How this process is directed and accomplished has been a mystery for a very long time,” says Bezanilla. But clearly, the scientist adds, microtubules are needed here because without them the cell plate does not form. “And we’ve known for a very long time that actin filaments are there in the structure, but nobody knew what they were for. What steers phragmoplast expansion at the molecular level was just not understood.”
“Our new paper proposes a model showing how plant cells steer their cell division machinery into position and how actin contributes. Our data from experiments in moss and tobacco provide evidence that a protein called myosin VIII, along with actin, guide cytokinesis. It answers what has been an open question in cell biology for decades.”
Using a state-of-the-art microscope funded by the Massachusetts Life Sciences Institute at UMass Amherst, she and Wu were able to watch key structures taking shape, label them and make videos of cytokinesis for hours to piece together how actin, microtubules and the structural protein known as myosin VIII cooperate to accomplish proper division.
“What’s unique with this myosin is that it can also interact with microtubules and in fact we think the microtubules are its cargo,” Bezanilla says. “We think the myosin is pulling the microtubule along an actin filament.” Crosstalk between actin and microtubules is something that happens in all cells so this work in plants could have implications in animal cell processes as well, Bezanilla says.
She adds, “Some of these things were just at the edge of being visible. It was quite a feat to be able to image the process for such a long time and to witness a live cell process.”
Overall, using a combination of genetics and live-cell imaging to query what guides the phragmoplast, the scientists identified actin and actin-based molecular motors, the class VIII myosins, as a key to the steering mechanism for cytokinesis in these plant cells. Their paper describes step by step how it unfolds.
Reference: Shu-Zon Wu, Magdalena Bezanilla. Myosin VIII associates with microtubule ends and together with actin plays a role in guiding plant cell division. eLife, 2014; 3 DOI: 10.7554/eLife.03498
Using the Atacama Large Millimeter/submillimeter Array, known as the ALMA Observatory, a group of radio telescopes funded partially through the National Science Foundation, researchers studied the gaseous star-forming region Sagittarius B2.
Astronomers from Cornell, the Max Planck Institute for Radio Astronomy and the University of Cologne (Germany) describe their discovery in the journal Science (Sept. 26.)
Organic molecules usually found in these star-forming regions consist of a single “backbone” of carbon atoms arranged in a straight chain. But the carbon structure of isopropyl cyanide branches off, making it the first interstellar detection of such a molecule, says Rob Garrod, Cornell senior research associate at the Center for Radiophysics and Space Research.
This detection opens a new frontier in the complexity of molecules that can be formed in interstellar space and that might ultimately find their way to the surfaces of planets, says Garrod. The branched carbon structure of isopropyl cyanide is a common feature in molecules that are needed for life — such as amino acids, which are the building blocks of proteins. This new discovery lends weight to the idea that biologically crucial molecules, like amino acids that are commonly found in meteorites, are produced early in the process of star formation — even before planets such as Earth are formed.
Garrod, along with lead author Arnaud Belloche and Karl Menten, both of the Max Planck Institute for Radio Astronomy, and Holger Müller, of the University of Cologne, sought to examine the chemical makeup of Sagittarius B2, a region close to the Milky Way’s galactic center and an area rich in complex interstellar organic molecules.
With ALMA, the group conducted a full spectral survey — looking for fingerprints of new interstellar molecules — with sensitivity and resolution 10 times greater than previous surveys.
The purpose of the ALMA Observatory is to search for cosmic origins through an array of 66 sensitive radio antennas from the high elevation and dry air of northern Chile’s Atacama Desert. The array of radio telescopes works together to form a gigantic “eye” peering into the cosmos.
“Understanding the production of organic material at the early stages of star formation is critical to piecing together the gradual progression from simple molecules to potentially life-bearing chemistry,” said Belloche.
About 50 individual features for isopropyl cyanide (and 120 for normal-propyl cyanide, its straight-chain sister molecule) were identified in the ALMA spectrum of the Sagittarius B2 region. The two molecules — isopropyl cyanide and normal-propyl cyanide — are also the largest molecules yet detected in any star-forming region.
Reference: A. Belloche, R. T. Garrod, H. S. P. Muller, K. M. Menten. Detection of a branched alkyl molecule in the interstellar medium: iso-propyl cyanide. Science, 2014; 345 (6204): 1584 DOI: 10.1126/science.1256678
Water is found throughout our Solar System. Not just on Earth, but on icy comets and moons, and in the shadowed basins of Mercury. Water has been found included in mineral samples from meteorites, the Moon, and Mars.
Comets and asteroids in particular, being primitive objects, provide a natural “time capsule” of the conditions during the early days of our Solar System. Their ices can tell scientists about the ice that encircled the Sun after its birth, the origin of which was an unanswered question until now.
In its youth, the Sun was surrounded by a protoplanetary disk, the so-called solar nebula, from which the planets were born. But it was unclear to researchers whether the ice in this disk originated from the Sun’s own parental interstellar molecular cloud, from which it was created, or whether this interstellar water had been destroyed and was re-formed by the chemical reactions taking place in the solar nebula.
“Why this is important? If water in the early Solar System was primarily inherited as ice from interstellar space, then it is likely that similar ices, along with the prebiotic organic matter that they contain, are abundant in most or all protoplanetary disks around forming stars,” Alexander explained. “But if the early Solar System’s water was largely the result of local chemical processing during the Sun’s birth, then it is possible that the abundance of water varies considerably in forming planetary systems, which would obviously have implications for the potential for the emergence of life elsewhere.”
In studying the history of our Solar System’s ices, the team — led by L. Ilsedore Cleeves from the University of Michigan — focused on hydrogen and its heavier isotope deuterium. Isotopes are atoms of the same element that have the same number of protons but a different number of neutrons. The difference in masses between isotopes results in subtle differences in their behavior during chemical reactions. As a result, the ratio of hydrogen to deuterium in water molecules can tell scientists about the conditions under which the molecules formed.
For example, interstellar water-ice has a high ratio of deuterium to hydrogen because of the very low temperatures at which it forms. Until now, it was unknown how much of this deuterium enrichment was removed by chemical processing during the Sun’s birth, or how much deuterium-rich water-ice the newborn Solar System was capable of producing on its own.
So the team created models that simulated a protoplanetary disk in which all the deuterium from space ice has already been eliminated by chemical processing, and the system has to start over “from scratch” at producing ice with deuterium in it during a million-year period. They did this in order to see if the system can reach the ratios of deuterium to hydrogen that are found in meteorite samples, Earth’s ocean water, and “time capsule” comets. They found that it could not do so, which told them that at least some of the water in our own Solar System has an origin in interstellar space and pre-dates the birth of the Sun.
“Our findings show that a significant fraction of our Solar System’s water, the most-fundamental ingredient to fostering life, is older than the Sun, which indicates that abundant, organic-rich interstellar ices should probably be found in all young planetary systems,” Alexander said.
Reference: L. Ilsedore Cleeves, Edwin A. Bergin, Conel M. O’D. Alexander, Fujun Du, Dawn Graninger, Karin I. Öberg, and Tim J. Harries. The ancient heritage of water ice in the solar system. Science, 26 September 2014: 1590-1593 DOI: 10.1126/science.1258055
The study, published in the journal Current Biology, shows that the familiar anatomical features of birds — such as feathers, wings and wishbones — all first evolved piecemeal in their dinosaur ancestors over tens of millions of years.
However, once a fully functioning bird body shape was complete, an evolutionary explosion began, causing a rapid increase in the rate at which birds evolved. This led eventually to the thousands of avian species that we know today.
A team of researchers, led by the University of Edinburgh (UK) and including Swarthmore College Associate Professor of Statistics Steve C. Wang, examined the evolutionary links between ancient birds and their closest dinosaur relatives. They did this by analyzing the anatomical make-up of more than 850 body features in 150 extinct species and used statistical techniques to analyze their findings and assemble a detailed family tree.
Based on their findings from fossil records, researchers say the emergence of birds some 150 million years ago was a gradual process, as some dinosaurs became more bird-like over time. This makes it very difficult to draw a dividing line on the family tree between dinosaurs and birds.
Findings from the study support a controversial theory proposed in the 1940s that the emergence of new body shapes in groups of species could result in a surge in their evolution.
“The evolution of birds from their dinosaur ancestors was a landmark in the history of life,” says Wang. “This process was so gradual that if you traveled back in time to the Jurassic, you’d find that the earliest birds looked indistinguishable from many other dinosaurs.”
Wang invented a novel statistical method that was able to take advantage of new kinds of data from the fossil record, which reached the conclusion that early birds had a high rate of evolution. He adds that “birds as we know them evolved over millions of years, accumulating small shifts in shape and function of the skeleton. But once all these pieces were in place to form the archetypal bird skeleton, birds then evolved rapidly, eventually leading to the great diversity of species we know today.”
“There was no moment in time when a dinosaur became a bird, and there is no single missing link between them, ” says Steve Brusatte of the University of Edinburgh’s School of GeoSciences, who led the study. “What we think of as the classic bird skeleton was pieced together gradually over tens of millions of years. Once it came together fully, it unlocked great evolutionary potential that allowed birds to evolve at a super-charged rate.”
Reference: Stephen L. Brusatte, Graeme T. Lloyd, Steve C. Wang, Mark A. Norell. Gradual Assembly of Avian Body Plan Culminated in Rapid Rates of Evolution across the Dinosaur-Bird Transition. Current Biology, 2014; DOI: 10.1016/j.cub.2014.08.034
Astronomers have studied galactic evolution for decades, gradually improving our knowledge of how galaxies have changed over cosmic history. The NASA/ESA Hubble Space Telescope has played a big part in this, allowing astronomers to see further into the distance, and hence further back in time, than any telescope before it — capturing light that has taken billions of years to reach us.
Looking further into the very distant past to observe younger and younger galaxies is very valuable, but it is not without its problems for astronomers. All newly-born galaxies lie very far away from us and appear very small and faint in the images. On the contrary, all the galaxies near to us appear to be old ones.
DDO 68, captured here by the NASA/ESA Hubble Space Telescope, was one of the best candidates so far discovered for a newly-formed galaxy in our cosmic neighbourhood. The galaxy lies around 39 million light-years away from us; although this distance may seem huge, it is in fact roughly 50 times closer than the usual distances to such galaxies, which are on the order of several billions of light years.
By studying galaxies of various ages, astronomers have found that those early in their lives are fundamentally different from those that are older. DDO 68 looks to be relatively youthful based on its structure, appearance, and composition. However, without more detailed modelling astronomers cannot be sure and they think it may be older than it lets on.
Elderly galaxies tend to be larger thanks to collisions and mergers with other galaxies that have bulked them out, and are populated with a variety of different types of stars — including old, young, large, and small ones. Their chemical makeup is different too. Newly-formed galaxies have a similar composition to the primordial matter created in the Big Bang (hydrogen, helium and a little lithium), while older galaxies are enriched with heavier elements forged in stellar furnaces over multiple generations of stars.
DDO 68 is the best representation yet of a primordial galaxy in the local Universe as it appears at first glance to be very low in heavier elements — whose presence would be a sign of the existence of previous generations of stars.
Hubble observations were carried out in order to study the properties of the galaxy’s light, and to confirm whether or not there are any older stars in DDO 68. If there are, which there seem to be, this would disprove the hypothesis that it is entirely made up of young stars. If not, it would confirm the unique nature of this galaxy. More complex modelling is needed before we can know for sure but Hubble’s picture certainly gives us a beautiful view of this unusual object.
The discovery published online Wednesday in the journal Nature contradicts several longstanding interpretations of multicellular fossils from at least 600 million years ago.
“This opens up a new door for us to shine some light on the timing and evolutionary steps that were taken by multicellular organisms that would eventually go on to dominate the Earth in a very visible way,” said Shuhai Xiao, a professor of geobiology in the Virginia Tech College of Science. “Fossils similar to these have been interpreted as bacteria, single-cell eukaryotes, algae, and transitional forms related to modern animals such as sponges, sea anemones, or bilaterally symmetrical animals. This paper lets us put aside some of those interpretations.”
In an effort to determine how, why, and when multicellularity arose from single-celled ancestors, Xiao and his collaborators looked at phosphorite rocks from the Doushantuo Formation in central Guizhou Province of South China, recovering three-dimensionally preserved multicellular fossils that showed signs of cell-to-cell adhesion, differentiation, and programmed cell death — qualities of complex multicellular eukaryotes such as animals and plants.
The discovery sheds light on how and when solo cells began to cooperate with other cells to make a single, cohesive life form.
The complex multicellularity evident in the fossils is inconsistent with the simpler forms such as bacteria and single-celled life typically expected 600 million years ago.
While some hypotheses can now be discarded, several interpretations may still exist, including the multicellular fossils being transitional forms related to animals or multicellular algae.
Xiao said future research will focus on a broader paleontological search to reconstruct the complete life cycle of the fossils.
Xiao earned his bachelor’s and master’s degrees from Beijing University in 1988 and 1991 and his doctoral degree from Harvard University in 1998. He worked for three years at Tulane University before arriving at Virginia Tech in 2003.
He is currently active in an editorial role for seven professional publications and has published more than 130 papers.
Reference: Lei Chen, Shuhai Xiao, Ke Pang, Chuanming Zhou, Xunlai Yuan. Cell differentiation and germ–soma separation in Ediacaran animal embryo-like fossils. Nature, 2014; DOI: 10.1038/nature13766