Genomics

dna-from-mammoth-remains-reveals-the-history-of-the-last-surviving-population

DNA from mammoth remains reveals the history of the last surviving population

ancient DNA, Biology, evolution, Genetics, Genomics, mammoths, Science, Wrangel Island / /

Sole survivors —

The mammoths of Wrangel Island purged a lot of harmful mutations before dying off.

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A dark, snowy vista with a single mammoth walking past the rib cage of another of its kind.

Enlarge / An artist’s conception of one of the last mammoths of Wrangel Island.

Beth Zaiken

A small group of woolly mammoths became trapped on Wrangel Island around 10,000 years ago when rising sea levels separated the island from mainland Siberia. Small, isolated populations of animals lead to inbreeding and genetic defects, and it has long been thought that the Wrangel Island mammoths ultimately succumbed to this problem about 4,000 years ago.

A paper in Cell on Thursday, however, compared 50,000 years of genomes from mainland and isolated Wrangel Island mammoths and found that this was not the case. What the authors of the paper discovered not only challenges our understanding of this isolated group of mammoths and the evolution of small populations, it also has important implications for conservation efforts today.

A severe bottleneck

It’s the culmination of years of genetic sequencing by members of the international team behind this new paper. They studied 21 mammoth genomes—13 of which were newly sequenced by lead author Marianne Dehasque; others had been sequenced years prior by co-authors Patrícia Pečnerová, Foteini Kanellidou, and Héloïse Muller. The genomes were obtained from Siberian woolly mammoths (Mammuthus primigenius), both from the mainland and the island before and after it became isolated. The oldest genome was from a female Siberian mammoth who died about 52,300 years ago. The youngest were from Wrangel Island male mammoths who perished right around the time the last of these mammoths died out (one of them died just 4,333 years ago).

Wrangel Island, north of Siberia has an extensive tundra.

Enlarge / Wrangel Island, north of Siberia has an extensive tundra.

Love Dalén

It’s a remarkable and revealing time span: The sample included mammoths from a population that started out large and genetically healthy, went through isolation, and eventually went extinct.

Mammoths, the team noted in their paper, experienced a “climatically turbulent period,” particularly during an episode of rapid warming called the Bølling-Allerød interstadial (approximately 14,700 to 12,900 years ago)—a time that others have suggested might have led to local woolly mammoth extinctions. However, the genomes of mammoths studied through this time period don’t indicate that the warming had any adverse effects.

Adverse effects only appeared—and drastically so—once the population was isolated on that island.

The team’s simulations indicate that, at its smallest, the total population of Wrangel Island mammoths was fewer than 10 individuals. This represents a severe population bottleneck. This was seen genetically through increased runs of homozygosity within the genome, caused when both parents contribute nearly identical chromosomes, both derived from a recent ancestor. The runs of homozygosity within isolated Wrangel Island mammoths were four times as great as those before sea levels rose.

Despite that dangerously tiny number of mammoths, they recovered. The population size, as well as inbreeding level and genetic diversity, remained stable for the next 6,000 years until their extinction. Unlike the initial population bottleneck, genomic signatures over time seem to indicate inbreeding eventually shifted to pairings of more distant relatives, suggesting either a larger mammoth population or a change in behavior.

Within 20 generations, their simulations indicate, the population size would have increased to about 200–300 mammoths. This is consistent with the slower decrease in heterozygosity that they found in the genome.

Long-lasting negative effects

The Wrangel Island mammoths may have survived despite the odds, and harmful genetic defects may not have been the reason for their extinction, but the research suggests their story is complicated.

At about 7,608 square kilometers today, a bit larger than the island of Crete, Wrangel Island would have offered a fair amount of space and resources, although these were large animals. For 6,000 years following their isolation, for example, they suffered from inbreeding depression, which refers to increased mortality as a result of inbreeding and its resulting defects.

That inbreeding also boosted the purging of harmful mutations. That may sound like a good thing—and it can be—but it typically occurs because individuals carrying two copies of harmful mutations die or fail to reproduce. So it’s good only if the population survives it.

The team’s results show that purging genetic mutations can be a lengthy evolutionary process. Lead author Marianne Dehasque is a paleogeneticist who completed her PhD at the Centre for Palaeogenetics. She explained to Ars that, “Purging harmful mutations for over 6,000 years basically indicates long-lasting negative effects caused by these extremely harmful mutations. Since purging in the Wrangel Island population went on for such a long time, it indicates that the population was experiencing negative effects from these mutations up until its extinction.”

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DNA parasite now plays key role in making critical nerve cell protein

Biology, evolution, Genetics, Genomics, myelin, neurobiology, Science, transposons / /

Domesticated viruses —

An RNA has been adopted to help the production of myelin, a key nerve protein.

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Graphic depiction of a nerve cell with a myelin coated axon.

Human brains (and the brains of other vertebrates) are able to process information faster because of myelin, a fatty substance that forms a protective sheath over the axons of our nerve cells and speeds up their impulses. How did our neurons evolve myelin sheaths? Part of the answer—which was unknown until now—almost sounds like science fiction.

Led by scientists from Altos Labs-Cambridge Institute of Science, a team of researchers has uncovered a bit of the gnarly past of how myelin ended up covering vertebrate neurons: a molecular parasite has been messing with our genes. Sequences derived from an ancient virus help regulate a gene that encodes a component of myelin, helping explain why vertebrates have an edge when it comes to their brains.

Prehistoric infection

Myelin is a fatty material produced by oligodendrocyte cells in the central nervous system and Schwann cells in the peripheral nervous system. Its insulating properties allow neurons to zap impulses to one another at faster speeds and greater lengths. Our brains can be complex in part because myelin enables longer, narrower axons, which means more nerves can be stacked together.

The un-myelinated brain cells of many invertebrates often need to rely on wider—and therefore fewer—axons for impulse conduction. Rapid impulse conduction makes quicker reactions possible, whether that means fleeing danger or capturing prey.

So, how do we make myelin? A key player in its production appears to be a type of molecular parasite called a retrotransposon.

Like other transposons, retrotransposons can move to new locations in the genome through an RNA intermediate. However, most retrotransposons in our genome have picked up too many mutations to move about anymore.

RNLTR12-int is a retrotransposon that is thought to have originally entered our ancestors’ genome as a virus. Rat genomes now have over 100 copies of the retrotransposon.

An RNA made by RNLTR12-int helps produce myelin by binding to a transcription factor or a protein that regulates the activity of other genes. The RNA/protein combination binds to DNA near the gene for myelin basic protein, or MBP, a major component of myelin.

“MBP is essential for the membrane growth and compression of [central nervous system] myelin,” the researchers said in a study recently published in Cell.

Technical knockout

To find out whether RNLTR12-int really was behind the regulation of MBP and, therefore, myelin production, the research team had to knock its level down and see if myelination still happened. They first experimented on rat brains before moving on to zebrafish and frogs.

When they inhibited RNLTR12-int, the results were drastic. In the central nervous system, genetically edited rats produced 98 percent less MBP than those where the gene was left unedited. The absence of RNLTR12-int also caused the oligodendrocytes that produce myelin to develop much simpler structures than they would normally form. When RNLTR12-int was knocked out in the peripheral nervous system, it reduced myelin produced by Schwann cells.

The researchers used a SOX10 antibody to show that SOX10 bound to the RNLTR12-int transcript in vivo. This was an important result, since there are lots of non-coding RNAs made by cells, and it wasn’t clear whether any RNA would work or if it was specific to RNLTR12-int.

Do these results hold up in other jawed vertebrates? Using CRISPR-CAS9 to perform knockout tests with retrotransposons related to RNLTR12-int in frogs and zebrafish showed similar results.

Myelination has enriched the vertebrate brain so it can work like never before. This is why the term “brain food” is literal. Healthy fats are so important for our brains; they help form myelin since it is a fatty acid. Think about that next time you’re pulling an all-nighter while reaching for a handful of nuts.

Cell, 2024. DOI: 10.1016/j.cell.2024.01.011

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Gotta go? We’ve finally found out what makes urine yellow

biochemistry, Biology, Genomics, Science, urine / /

It isn’t from eating corn —

The yellow color comes from bacteria metabolizing waste from red blood cells.

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Image of a series of scientific sample tubes filled with yellow liquids.

There are many mysteries in life that we end up shrugging off. Why is urine yellow? It just is, right? Rather than flush that 125-year-old question down the toilet, scientists sought out the answer, discovering a previously unknown microbial enzyme was to blame.

The enzyme that has eluded us for so long is now known as bilirubin reductase. It was identified by researcher and assistant professor Brantley Hall of the University of Maryland, who was part of a team based at the university and the National Institutes of Health.

Bilirubin is an orange pigment released by red blood cells after they die. Gut microbes then use bilirubin reductase to break down bilirubin into colorless urobilinogen, which degrades into yellowish urobilin, giving urine that infamous hue. While urobilin previously had an association with the color of urine, the enzyme that starts the process by producing urobilinogen was unknown until now.

“Though it was previously thought that multiple enzymes were involved in the reduction of bilirubin, our results support the finding that a single enzyme performs the reduction of bilirubin to urobilinogen,” the research team said in a study recently published in Nature Microbiology.

Gut feeling

Because some gut bacteria had been known to reduce bilirubin, Hall and his team knew where to start but wanted to fill in the unknowns by finding out which particular species actually do this—and how. This meant they had to find the gene responsible for encoding bilirubin reductase.

Previous studies had found that the species Clostridiodes difficile was capable of reducing bilirubin (though the mechanism it used was unknown). Using C. difficile as a basis for comparison, the team cultured different species of gut bacteria and exposed them to bilirubin to see whether that bacteria could produce urobilinogen, detecting its presence using a fluorescence assay.

The fluorescence assay told Hall and his colleagues that there were nine strains within the tested species that they thought were capable of reducing bilirubin, although how these bacteria were breaking it down was still unclear.  After the fluorescence assay, the genomes of the most closely related strains were analyzed,  and several turned out to share a gene that encoded an enzyme that could reduce bilirubin—bilirubin reductase.

Bacterial strains that metabolized bilirubin using bilirubin reductase all came from species that were found to belong to a single clade (the researchers informally referred to it as the bilirubin reductase clade). Within that clade, most of these species are from the class Clostridia in the phylum Firmicutes, a phylum of bacteria important to gut health.

More than … you know

The discovery of bilirubin reductase goes beyond the origin of urine color. After identifying the enzyme, the researchers found out that, while bilirubin reductase is present in healthy adults, there is a deficit in newborns and adults with inflammatory bowel disease, which could eventually influence future treatments

By sequencing infant gut genomes, Hall and his team saw that bilirubin reductase was often missing during the first few months of life. Too much bilirubin building up in the blood turns the skin and the whites of the eyes yellow, a symptom known as jaundice. Most infants have some level of jaundice, but it usually goes away on its own.

The absence of bilirubin reductase is also associated with pigmented gallstones in adults with inflammatory bowel disease (inflammatory bowel disease or IBD is a general term that can refer to several different diagnoses). Sequencing adult gut genomes showed that there was a deficit of this enzyme in most patients with Crohn’s disease or ulcerative colitis whose gut genomes were sequenced.

“With the knowledge of the species, genes, and enzymes involved in bilirubin reduction, future research can now focus on the extent to which gut microbial bilirubin metabolism affects…the role of bilirubin reduction in health and disease,” the researchers said in the same study.

There is still more research to be done on bilirubin reductase and the health implications it could have. The team thinks there may be a link between the amount of urobilin produced in the body and insulin resistance, obesity, heart disease, and even heart failure. Next to that, we finally know why urine is yellow.

Nature Microbiology, 2023. DOI: 10.1038/s41564-023-01549-x

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Getting to the bottom of how red flour beetles absorb water through their butts

12 days of Christmas, agricultural sciences, animals, beetles, Biology, Biomechanics, genomes, Genomics, red flour beetle, Science / /

On the third day of Christmas —

A unique group of cells pumps water into the kidneys to help harvest moisture from the air.

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Who <em>doesn’t</em> thrill to the sight of a microscopic cross-section of a beetle’s rectum? You’re welcome.” src=”https://cdn.arstechnica.net/wp-content/uploads/2023/03/beetle-butt-TOP-800×536.jpg”></img><figcaption> <p><a data-height=Enlarge / Who doesn’t thrill to the sight of a microscopic cross-section of a beetle’s rectum? You’re welcome.

Kenneth Veland Halberg

There’s rarely time to write about every cool science-y story that comes our way. So this year, we’re once again running a special Twelve Days of Christmas series of posts, highlighting one science story that fell through the cracks in 2023, each day from December 25 through January 5. Today: red flour beetles can use their butts to suck water from the air, helping them survive in extremely dry environments. Scientists are honing in on the molecular mechanisms behind this unique ability.

The humble red flour beetle (Tribolium castaneum) is a common pantry pest feeding on stored grains, flour, cereals, pasta, biscuits, beans, and nuts. It’s a remarkably hardy creature, capable of surviving in harsh arid environments due to its unique ability to extract fluid not just from grains and other food sources, but also from the air. It does this by opening its rectum when the humidity of the atmosphere is relatively high, absorbing moisture through that opening and converting it into fluid that is then used to hydrate the rest of the body.

Scientists have known about this ability for more than a century, but biologists are finally starting to get to the bottom (ahem) of the underlying molecular mechanisms, according to a March paper published in the Proceedings of the National Academies of Science. This will inform future research on how to interrupt this hydration process to better keep red flour beetle populations in check, since they are highly resistant to pesticides. They can also withstand even higher levels of radiation than the cockroach.

There are about 400,000 known species of beetle roaming the planet although scientists believe there could be well over a million. Each year, as much as 20 percent of the world’s grain stores are contaminated by red flour beetles, grain weevils, Colorado potato beetles, and confused flour beetles, particularly in developing countries. Red flour beetles in particular are a popular model organism for scientific research on development and functional genomics. The entire genome was sequenced in 2008, and the beetle shares between 10,000 and 15,000 genes with the fruit fly (Drosophila), another workhorse of genetics research. But the beetle’s development cycle more closely resembles that of other insects by comparison.

Food security in developing nations is particularly affected by animal species like the red flour beetle which has specialized in surviving in extremely dry environments, granaries included, for thousands of years.

Enlarge / Food security in developing nations is particularly affected by animal species like the red flour beetle which has specialized in surviving in extremely dry environments, granaries included, for thousands of years.

Kenneth Halberg

The rectums of most mammals and insects absorb any remaining nutrients and water from the body’s waste products prior to defecation. But the red flour beetle’s rectum is a model of ultra-efficiency in that regard. The beetle can generate extremely high salt concentrations in its kidneys, enabling it to extract all the water from its own feces and recycle that moisture back into its body.

“A beetle can go through an entire life cycle without drinking liquid water,” said co-author Kenneth Veland Halberg, a biologist at the University of Copenhagen. “This is because of their modified rectum and closely applied kidneys, which together make a multi-organ system that is highly specialized in extracting water from the food that they eat and from the air around them. In fact, it happens so effectively that the stool samples we have examined were completely dry and without any trace of water.” The entire rectal structure is encased in a perinephric membrane.

Halberg et al. took took scanning electron microscopy images of the beetle’s rectal structure. They also took tissue samples and extracted RNA from lab-grown red flour beetles, then used a new resource called BeetleAtlas for their gene expression analysis, hunting for any relevant genes.

One particular gene was expressed sixty times more in the rectum than any other. Halberg and his team eventually honed in a group of secondary cells between the beetle’s kidneys and circulatory system called leptophragmata. This finding supports prior studies that suggested these cells might be relevant since they are the only cells that interrupt the perinephric membrane, thereby enabling critical transport of potassium chloride. Translation: the cells pump salts into the kidneys to better harvest moisture from its feces or from the air.

Model of the beetle's inside and how it extracts water from the air.

Enlarge / Model of the beetle’s inside and how it extracts water from the air.

Kenneth Halberg

The next step is to build on these new insights to figure out how to interrupt the beetle’s unique hydration process at the molecular level, perhaps by designing molecules that can do so. Those molecules could then be incorporated into more eco-friendly pesticides that target the red flour beetle and similar pests while not harming more beneficial insects like bees.

“Now we understand exactly which genes, cells and molecules are at play in the beetle when it absorbs water in its rectum. This means that we suddenly have a grip on how to disrupt these very efficient processes by, for example, developing insecticides that target this function and in doing so, kill the beetle,” said Halberg. “There is twenty times as much insect biomass on Earth than that of humans. They play key roles in most food webs and have a huge impact on virtually all ecosystems and on human health. So, we need to understand them better.”

DOI: PNAS, 2023. 10.1073/pnas.2217084120  (About DOIs).

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