In the beginning was the phase separation

The question of the origin of life remains one of the oldest unanswered scientific questions. A team at the Technical University of Munich (TUM) has now shown for the first time that phase separation is an extremely efficient way of controlling the selection of chemical building blocks and providing advantages to certain molecules.

A team at the Technical University of Munich (TUM) has shown for the first time, that phase separation is an extremely
efficient way of controlling the selection of chemical building blocks, providing advantages to certain molecules.
This simple mechanism could have been decisive for the development of life. Left: clear solution; right: inside
 the tiny oil droplets instable molecules survive longer [Credit: Andreas Battenberg/TUM]

Life needs energy. Without energy, cells cannot move or divide, not even basic functions such as the production of simple proteins could be maintained. If energy is lacking, more complex connections disintegrate quickly, early life would die immediately.

Chemist Job Boekhoven and his team at TUM have now succeeded in using phase separation to find a mechanism in simple molecules that enables extremely unstable molecules such as those found in the primordial soup to have a higher degree of stability. They could survive longer, even if they had to survive a period without external energy supply.

The principle of simplicity

Job Boekhoven and his team were looking for a simple mechanism with primitive molecules that could produce life-like properties. "Most likely, molecules were simple in the primordial soup," says Boekhoven. The researchers investigated what happens when they "fed" various carboxylic acid molecules with high-energy carbodiimide condensing agents, thus bringing them out of equilibrium.

The reaction produces unstable anhydrides. In principle, these non-equilibrium products quickly disintegrate into carboxylic acids again. The scientists showed that the anhydrides that survived the longest were those that could form a kind of oil droplet in the aqueous environment.

Single droplets under a fluorescence microscope [Credit: Marta Tena-Solsona/TUM]

Molecules in the garage

The effect can also be seen externally: the initially clear solution becomes milky. The lack of water in the oil droplets is like a protection because anhydrides need water to disintegrate back into carboxylic acids.

Boekhoven explains the principle of phase separation with an analogy: "Imagine an old and rusty car: Leave it outside in the rain, and it continues to rust and decomposes because rusting is accelerated by water. Put it in the garage, and it stops rusting because you separate it from the rain."

In a way, a similar process occurs in the primordial soup experiment: Inside the oil droplet (garage) with the long-chain anhydride molecules there is no water, so its molecules survive longer. If the molecules compete with each other for energy, again those that can protect themselves by forming oil droplets are likelier to survive, while their competitors get hydrolyzed.

Next goal: viable information carriers

Since the mechanism of phase separation is so simple, it can possibly be extended to other types of molecular aggregations with life-like properties such as DNA, RNA or self-dividing vesicles. Studies have shown that these bubbles can divide spontaneously. "Soon we hope to turn primitive chemistry into a self-replicating information carrier that is protected from decay to a certain extent," says Boekhoven.

The study is published in Nature Communications.

Source: Technical University of Munich [May 23, 2018]

Far from special: Humanity's tiny DNA differences are 'average' in animal kingdom

Researchers report important new insights into evolution following a study of mitochondrial DNA from about 5 million specimens covering about 100,000 animal species.

Today's study, "Why should mitochondria define species?" published as an open-access article in the journal
Human Evolution,builds on earlier work by Drs. Stoeckle and Thayer, including an examination of the
mitochondrial genetic diversity of humans vs. our closest living and extinct relatives. The amount of
color variation within each red box of the Klee diagram illustrates the far greater mitochondrial
diversity among chimpanzees and bonobos than among living humans
[Credit: The Rockefeller University]

Mining "big data" insights from the world's fast-growing genetic databases and reviewing a large literature in evolutionary theory, researchers at The Rockefeller University in New York City and the Biozentrum at the University of Basel in Switzerland, published several conclusions today in the journal Human Evolution. Among them:

• - In genetic diversity terms, Earth's 7.6 billion humans are anything but special in the animal kingdom. The tiny average genetic difference in mitochondrial sequences between any two individual people on the planet is about the same as the average genetic difference between a pair of the world's house sparrows, pigeons or robins. The typical difference within a species, including humans, is 0.1% or 1 in 1,000 of the "letters" that make up a DNA sequence.

• - Genetic variation - the average difference in mitochondria DNA between two individuals of the same species - does not increase with population size. Because evolution is relentless, however, the lack of genetic variation offers insights into the timing of a species' emergence and its maintenance.

• - The mass of evidence supports the hypothesis that most species, be it a bird or a moth or a fish, like modern humans, arose recently and have not had time to develop a lot of genetic diversity. The 0.1% average genetic diversity within humanity today corresponds to the divergence of modern humans as a distinct species about 100,000 - 200,000 years ago - not very long in evolutionary terms. The same is likely true of over 90% of species on Earth today.

• - Genetically the world "is not a blurry place." Each species has its own specific mitochondrial sequence and other members of the same species are identical or tightly similar. The research shows that species are "islands in sequence space" with few intermediate "stepping stones" surviving the evolutionary process.

Among 1st "big data" insights from a growing collection of mitochondrial DNA

"DNA barcoding" is a quick, simple technique to identify species reliably through a short DNA sequence from a particular region of an organism. For animals, the preferred barcode regions are in mitochondria - cellular organelles that power all animal life.

The new study, "Why should mitochondria define species?" relies largely on the accumulation of more than 5 million mitochondrial barcodes from more than 100,000 animal species, assembled by scientists worldwide over the past 15 years in the open access GenBank database maintained by the US National Center for Biotechnology Information.

The researchers have made novel use of the collection to examine the range of genetic differences within animal species ranging from bumblebees to birds and reveal surprisingly minute genetic variation within most animal species, and very clear genetic distinction between a given species and all others.

"If a Martian landed on Earth and met a flock of pigeons and a crowd of humans, one would not seem more diverse than the other according to the basic measure of mitochondrial DNA," says Jesse Ausubel, Director of the Program for the Human Environment at The Rockefeller University, where the research was led by Senior Research Associate Mark Stoeckle and Research Associate David Thaler of the University of Basel, Switzerland.

The study results represent a surprise given predictions found in textbooks, and based on mathematical models of evolution,
 that the bigger the population of a species, the greater the genetic variation one expects to find. In fact, the mitochondrial
diversity within 7.6 billion humans or 500 million house sparrows or 100,000 sandpipers from around the world is about
 the same.The paper notes, however, that evolution is relentless, that species are always changing, and, therefore, the
degree of variation within a given species offers a clue into how long ago it emerged distinctly -- in other words,
 the older the species the greater the average genetic variation between its members
[Credit: The Rockefeller University]

"At a time when humans place so much emphasis on individual and group differences, maybe we should spend more time on the ways in which we resemble one another and the rest of the animal kingdom."

Says Dr. Stoeckle: "Culture, life experience and other things can make people very different but in terms of basic biology, we're like the birds."

"By determining the genetic variety within species of the animal kingdom, made possible only recently by the burgeoning number of DNA sequences, we've documented the absence of human exceptionalism."

Says. Dr. Thaler: "Our approach combines DNA barcodes, which are broad but not deep, from the entire animal kingdom with more detailed sequence information available for the entire mitochondrial genome of modern humans and a few other species. We analyzed DNA barcode sequences from thousands of modern humans in the same way as those from other animal species."

"One might have thought that, due to their high population numbers and wide geographic distribution, humans might have led to greater genetic diversity than other animal species," he adds. "At least for mitochondrial DNA, humans turn out to be low to average in genetic diversity."

"Experts have interpreted low genetic variation among living humans as a result of our recent expansion from a small population in which a sequence from one mother became the ancestor for all modern human mitochondrial sequences," says Dr. Thaler.

"Our paper strengthens the argument that the low variation in the mitochondrial DNA of modern humans also explains the similar low variation found in over 90% of living animal species - we all likely originated by similar processes and most animal species are likely young."

Genetic variation does not increase with population

The study results represent a surprise given predictions found in textbooks, and based on mathematical models of evolution, that the bigger the population of a species, the greater the genetic variation one expects to find.

"Is genetic diversity related to the size of the population?" asks Dr. Stoeckle. "The answer is no. The mitochondrial diversity within 7.6 billion humans or 500 million house sparrows or 100,000 sandpipers from around the world is about the same."

The paper notes, however, that evolution is relentless, that species are always changing, and, therefore, the degree of variation within a given species offers a clue into how long ago it emerged distinctly -- in other words, the older the species the greater the average genetic variation between its members.

Evolutionary bottlenecks: the fresh new beginning of a species

While asteroids and ice ages have played major roles in evolutionary history, scientists speculate that another great driver may have been the microbial world, notably viruses, which periodically cull populations, leaving behind only those able to survive the deadly challenge.

Genetically, 'the world is not a blurry place.' It is hard to find 'intermediates' -- the evolutionary stepping
stones between species. The intermediates disappear. The research is a new way to show that species
are 'islands in sequence space.' Each species has its own narrow, very specific consensus sequence,
just as our phone system has short, unique numeric codes to tell cities and countries apart
[Credit: The Rockefeller University]

"Life is fragile, susceptible to reductions in population from ice ages and other forms of environmental change, infections, predation, competition from other species and for limited resources, and interactions among these forces," says Dr. Thaler. Adds Dr. Thaler, "The similar sequence variation in many species suggests that all of animal life experiences pulses of growth and stasis or near extinction on similar time scales."

"Scholars have previously argued that 99% of all animal species that ever lived are now extinct. Our work suggests that most species of animals alive today are like humans, descendants of ancestors who emerged from small populations possibly with near-extinction events within the last few hundred thousand years."

'Islands in sequence space'

Another intriguing insight from the study, says Mr. Ausubel, is that "genetically, the world is not a blurry place. It is hard to find 'intermediates' - the evolutionary stepping stones between species. The intermediates disappear."

Dr. Thaler notes: "Darwin struggled to understand the absence of intermediates and his questions remain fruitful."

"The research is a new way to show that species are 'islands in sequence space.' Each species has its own narrow, very specific consensus sequence, just as our phone system has short, unique numeric codes to tell cities and countries apart."

Adds Dr. Thaler: "If individuals are stars, then species are galaxies. They are compact clusters in the vastness of empty sequence space."

The researchers say that with the bones or teeth of an ancient hominid, like those found in southern France or northern Spain, scientists might shed further light on the rate of evolution of the human species.

"It would be very exciting if over the next few years physical anthropologists and others were able to compare mitochondrial DNA from hominid species over the last 500,000 years," says Dr. Stoeckle.

Source: The Rockefeller University [May 21, 2018]

Genome structure of dinosaurs discovered by bird-turtle comparisons

A discovery by scientists at the University of Kent has provided significant insight into the overall genome structure of dinosaurs.

This is an Apalone spinifera spiny softshell turtle hatchling [Credit: Nicole Valenzuela]

By comparing the genomes of different species, chiefly birds and turtles, the Kent team were able to determine how the overall genome structure (i.e. the chromosomes) of many people's favourite dinosaur species - like Velociraptor or Tyrannosaurus - might have looked through a microscope.

The research was carried out in the laboratory of Professor Darren Griffin, of the University's School of Biosciences, and is now published in the journal Nature Communications. It involved extrapolating the likely genome structure of a shared common ancestor of birds and turtles that lived around 260 million years ago - 20 million years before the dinosaurs first emerged.

Dr Becky O'Connor, senior postdoctoral researcher and co-author of the paper, then traced how chromosomes changed over evolutionary time from a reptile ancestor to the present day.

The team found that, although the individual chromosomes rearranged their genes internally, this did not occur much at all between the chromosomes - what the scientists describe as 'a significant discovery'.

Birds (which are themselves living dinosaurs) have a lot of chromosomes compared to most other species and that is possibly one of the reasons why they are so diverse. This research suggests that the pattern of chromosomes (karyotype) seen in early emerging dinosaurs and later theropods is similar to that of most birds and, again, may help explain their great diversity.

The new discovery suggests that, had scientists had the opportunity to make a chromosome preparation from a theropod dinosaur, it might have looked very similar to that of a modern-day ostrich, duck or chicken.

One of the key pieces of biotechnology that made it possible was the development of a set of fluorescent probes derived from birds that worked well on the chromosomes of turtles.

Source: University of Kent [May 21, 2018]

Scientists analyze first ancient human DNA from Southeast Asia

The first whole-genome analyses of ancient human DNA from Southeast Asia reveal that there were at least three major waves of human migration into the region over the last 50,000 years.

Field workers excavate ancient human remains at Man Bac, Vietnam, in 2007. DNA from skeletons at this site
was included in the current study [Credit: Lorna Tilley, Australian National University]

The research, published in Science, complements what is known from archaeological, historical and linguistic studies of Southeast Asia, defined as the area east of India and south of China.

The work illuminates another critical portion of the story of ancient population dynamics around the world, joining numerous ancient-DNA studies of Europe as well as burgeoning research from the Near East, Central Asia, Pacific Islands and Africa.

"A very important part of the world is now accessible for ancient DNA analysis," said Mark Lipson, a postdoctoral fellow in the lab of ancient-DNA specialist David Reich at Harvard Medical School and first author of the study. "It opens a window into the genetic origins of the people who lived there in the past and those who live there now."

An international team led by researchers at HMS and the University of Vienna extracted and analyzed DNA from the remains of 18 people who lived between about 4,100 and 1,700 years ago in what are now Vietnam, Thailand, Myanmar and Cambodia.

The team found that the first migration took place about 45,000 years ago, bringing in people who became hunter-gatherers.

Then, during the Neolithic Period, around 4,500 years ago, there was a large-scale influx of people from China who introduced farming practices to Southeast Asia and mixed with the local hunter-gatherers.

People today with this ancestry mix tend to speak Austroasiatic languages, leading the researchers to propose that the farmers who came from the north were early Austroasiatic speakers.

"This study reveals a complex interplay between archaeology, genetics and language, which is critical for understanding the history of Southeast Asian populations," said co-senior author Ron Pinhasi of the University of Vienna.

The research revealed that subsequent waves of migration during the Bronze Age, again from China, arrived in Myanmar by about 3,000 years ago, in Vietnam by 2,000 years ago and in Thailand within the last 1,000 years. These movements introduced ancestry types that are today associated with speakers of different languages.

The identification of three ancestral populations -- hunter-gatherers, first farmers and Bronze Age migrants -- echoes a pattern first uncovered in ancient DNA studies of Europeans, but with at least one major difference: Much of the ancestral diversity in Europe has faded over time as populations mingled, while Southeast Asian populations have retained far more variation.

"People who are nearly direct descendants of each of the three source populations are still living in the region today, including people with significant hunter-gatherer ancestry who live in Thailand, Malaysia, the Philippines and the Andaman Islands," said Reich, professor of genetics at HMS and co-senior author of the study. "Whereas in Europe, no one living today has more than a small fraction of ancestry from the European hunter-gatherers."

Reich hypothesizes that the high diversity of Southeast Asia today can be partly explained by the fact that farmers arrived much more recently than in Europe -- around 4,500 years ago compared with 8,000 years ago -- leaving less time for populations to mix and genetic variation to even out.

The new findings make it clear that the multiple waves of migration, each of which occurred during a key transition period of Southeast Asian history, shaped the genetics of the region to a remarkable extent.

"The major population turnover that came with the arrival of farmers is unsurprising, but the magnitudes of replacement during the Bronze Age are much higher than many people would have guessed," said Reich.

Also unexpected were the linguistic implications raised by analyses of the ancestry of people in western Indonesia.

"The evidence suggests that the first farmers of western Indonesia spoke Austroasiatic languages rather than the Austronesian languages spoken there today," Reich added. "Thus, Austronesian languages were probably later arrivals."

Additional samples from western Indonesia before and after 4,000 years ago should settle the question, Reich said.

Source: Harvard Medical School [May 17, 2018]

Does evolution make us or are we just drifting that way?

Evolution may be responsible for a range of complex traits, including height and waist-to-hip ratio, and diseases such as schizophrenia, research from The University of Queensland shows.

Credit: Shutterstock

The findings improve understanding of how natural selection shapes human populations, and could lead to better prevention, diagnosis and treatment of complex diseases through an enhanced knowledge of their underlying genetics.

The study, led by Professor Jian Yang from UQ’s Institute for Molecular Bioscience and Queensland Brain Institute, used more than 400,000 genetic samples from African, East Asian and European populations.

“Many human complex traits are concentrated in different populations around the world,” Professor Yang said.

“For example, populations in the Northern Hemisphere tend to get taller the further north you go, and European Americans have a lower body mass index (BMI) than African Americans, but higher than Chinese, Indonesians or Thais.

“Environmental factors currently play a role, but most complex traits have a genetic component.

“The question is whether or not these differences are the consequence of natural selection or simply the result of what we call ‘genetic drift’ – where gene mutations (also called genetic variants) become more or less frequent in a population by chance.”

Professor Yang and his colleagues set out to answer the question by testing to see if genetic variants were more differentiated across African, East Asian and European populations than expected under genetic drift.

They looked at a range of complex traits – including height, BMI, waist-to-hip ratio and cholesterol levels – and four common diseases – coronary artery disease, type II diabetes, Alzheimer’s disease and schizophrenia.

If genetic variants associated with a complex trait resulted from natural selection they should appear more frequently than expected under genetic drift.

The analysis supported this, showing that the genetic variants associated with height, weight-to-hip ratio and schizophrenia were more differentiated than expected by random drift.

The genetic variants expected to affect height were higher in Europeans than Africans and East Asians and were consistent with observed differences between the populations.

“Our research was made possible by the availability of massive banks of genetic information that are being harnessed to shed new light on modifiable health risks that underlie common diseases.”

The methods developed in the study, published in Nature Communications, are general and applicable to other complex traits.

Source: University of Queensland [May 16, 2018]

What we inherited from our bug-eating ancestors

People who advocate adding insects to the human diet may be channeling their distant ancestors. Based on an analysis of the genomes of 107 different species of mammals, University of California, Berkeley, scientists conclude that our distant ancestors – the small, furry creatures that scurried around the feet of the dinosaurs 66 million years ago – were mostly insect eaters.

A spectral tarsier (Tarsius tarsier) feeding on a grasshopper in Tangkoko National Park, Northern Sulawesi, Indonesia
. Tarsiers have five chitinase genes to digest the high amount of chitin in their insectivorous diet, which likely
represents the ancestral condition of all placental animals, including humans
[Credit: Quentin Martinez]

The scientists inferred this because the genes for the enzymes that allowed these early ancestors of all mammals to digest insects are still hanging around in nearly all mammal genomes today. Even animals like tigers and seals that would never touch an insect have non-functional pieces of these genes sitting in their chromosomes, betraying their ancient ancestors’ diet.

“One of the coolest things is, if you look at humans, at Fido your dog, Whiskers your cat, your horse, your cow; pick any animal, generally speaking, they have remnants in their genomes of a time when mammals were small, probably insectivorous and running around when dinosaurs were still roaming Earth,” said postdoctoral fellow Christopher Emerling. “It is a signature in your genome that says, once upon a time you were not the dominant group of organisms on Earth. By looking at our genomes, we are looking at this ancestral past and a lifestyle that we don’t even live with anymore.”

The genetic evidence independently corroborates the conclusions paleontologists reached years ago based on the shapes of fossils and teeth from early mammals.

“In essence, we are looking at genomes and they are telling the same story as the fossils: that we think these animals were insectivorous and then dinosaurs went extinct. After the demise of these large carnivorous and herbivorous reptiles, mammals started changing their diets,” he said.

The finding could shed light on other roles played by these enzymes, called chitinases, which are found not only in the gut but the salivary glands, the pancreas and the lungs, where they may be involved in asthma.

Emerling and colleagues Michael Nachman, a professor of integrative biology and director of the UC Berkeley Museum of Vertebrate Zoology, and Frédéric Delsuc of the French National Center for Scientific Research (CNRS) and Université de Montpellier in France, report their findings in the journal Science Advances. Emerling currently is a PRESTIGE & Marie Curie postdoctoral fellow in Montpellier working on the ConvergeAnt project.

Breaking down insects’ exoskeletons

Many bacteria have genes that produce an enzyme that breaks down insects’ hard, outer shells, which are composed of a tough carbohydrate called chitin. It’s not surprising that humans and mice have a chitinase gene, since many humans today include insects in their diets, as do mice.

But humans actually have remnants of three other chitinase genes in their genome, though none of them are functional. Emerling showed that these gene remnants in humans aren’t unique to humans or primates, but instead can be traced to the ancestral placental mammals.

In all, he and his colleagues found five different chitinase enzyme genes by looking through the genomes of the largest group of mammals, those that have placentas that allow longer development in the womb, which excludes marsupials like opossums and egg-laying monotremes like the platypus. These placental mammals ranged from shrews and mice to elephants and whales.

Detailed artistic reconstruction of an ancestral placental mammal living during the Age of Dinosaurs 66 million
years ago, showing teeth adapted to capturing and eating insects [Credit: Carl Buell]

They found that the greater the percentage of insects in an animal’s diet, the more genes for chitinase it has.

“The only species that have five chitinases today are highly insectivorous, that is, 80 to 100 percent of their diet consists of insects. Since the earliest placental mammals likely had five chitinases, we think that this makes for a strong argument that they were highly insectivorous,” Emerling said.

As you would expect, ant and termite specialists such as aardvarks and certain armadillos have five functioning chitinase genes. But so do the insect-loving primates called tarsiers. They appear to be the only primates that have so many functional chitinase genes, Emerling said.

Dominated by dinosaurs

The story told by these chitinase genes is one of early mammals hunkering down eating insects while the big guys, the huge herbivorous dinosaurs like the brontosaurus and the big meat-eaters like T. rex gobbled up the most abundant food resources. Only 66 million years ago at the end of the Cretaceous Period, when all non-bird dinosaurs died out, were mammals able to expand into other niches, which they quickly did. The first carnivorous and herbivorous mammals, as indicated by their teeth, arose within 10 million years of the dinosaurs’ demise.

Emerling, who compares genomes to see how mammals and humans evolved, was interested in what mammal genomes could tell us about that transition from insectivory to herbivory and carnivory since the last mass extinction.

He focuses primarily on weird animals that eat insects, including anteaters and armadillos, the unrelated aardvark and the distantly related pangolin. In exploring how these animals are able to digest insects, he decided to look at chitinases, whose roles in mammals are still poorly understood. It’s not known, for example, whether the enzymes allow animals to break down chitin into its component sugars and use them for energy, or if chitinases’ sole function is to break up the exoskeleton to allow access to the soft interiors of insects.

Using databases of animal genomes, plus newly sequenced genomes of armadillos and a lesser anteater (tamandua) obtained by colleagues at the Broad Institute at MIT and Harvard, he searched for genes similar to the known chitinase gene and dredged up four new varieties.

Based on what is known about chitinase genes in bacteria and other animals, he was able to deduce which genes are functional and which are not, and draw conclusions about the tissues in which the genes are expressed and the enzyme active.

Among the surprises was that the insect-eating-specialist pangolin has only one functional chitinase gene, in contrast to the five in the aardvark and four in the lesser anteater. All eat ants and termites exclusively, but pangolins may have possibly evolved from carnivores that lost their chitinase genes shortly after taking over the ecological niche opened up when meat-eating dinosaurs died out.

Bison, gibbons and the dromedary camel have only one functional chitinase. Tigers, rhinos and polar bears have none.

Emerling has many other questions he thinks chitinases can answer about mammal evolution and physiology.

“This is suggesting that there are a lot of these enzymes that might be helping organisms digest their food. This goes from being a simple curiosity – humans have a chitinase, how cool! – to being something that can help us understand how different animals are adapted to their specialized diets.”

Source: University of California - Berkeley [May 16, 2018]