The week’s most astounding developments from the neobiological frontier.

January 13, 2022

DNA bonanza of Ice Age animals recovered in Canada

Exactly 125 years after the discovery of paydirt along the Klondike River set off one of the biggest clamoring for mineral claims the world had ever seen, another gold rush is underway in the central Canadian Yukon. This time the hidden treasures are not nuggets beneath forgotten river tributaries but biological samples buried for thousands of years in sub-zero permafrost. Researchers at McMaster University announced this week that a mere 1-gram sample of such silt yielded DNA traces of a number of long-extinct animals that lived in the area 30,000 years ago—from woolly mammoths to steppe bison to “stilt-legged” horses that once roamed North America. They used the DNA to reassemble 18 mitochondrial genomes of rodents, birds, and large mammals living at the end of the Ice Age Pleistocene period. Current Biology

Mustard greens choke out cherished evolutionary concept

A long-held dogma of evolutionary theory is what you might call the doctrine of dumb luck: The idea that at the molecular level, evolution is driven by random DNA mutations that sometimes lead to the emergence of new traits, the fittest of which are naturally selected for and become common genetic features. But new research with the lowly mustard green Arabidopsis thaliana defies that idea, showing that some regions of the plant’s DNA are less likely to mutate than others—a phenomenon known as “mutation bias.” In a large-scale evolutionary experiment, scientists at the Max Planck Institute for Biology in Tübingen, Germany and the University of California, Davis showed that mutations are reduced in essential genes and other areas of the genome via epigenetic mechanisms. This represents a significant challenge to the prevailing paradigm that mutation is a random, rudderless force in evolution. Nature

Normal mice see increase in brain plasticity from enriched microbiomes

Raising animals in enriched environments with enhanced access to environmental stimuli such as social interaction and motor activity can have profound benefits on the animals’ neural plasticity and cognition. Little is known about how environmental cues actually induce such profound changes in the brain, but it has been thought to somehow involve unknown mechanisms within the central nervous system. But now researchers at the University of Pisa in Italy are reporting a stunning result suggesting that environmental experiences impact brain plasticity through the gut microbiome. They looked at intestinal bacteria and short-chain fatty acid levels of normal mice and rodents raised in enriched environments, and they found the latter had significant changes to the composition of their gut microbiota. Transferring stool from these enriched mice into the guts of normal mice increased their neuroplasticity as well. Cell Reports

Next-generation gene-editing/payload-packaging platform delivers

Researchers at the Broad Institute of MIT and Harvard led by base-editing pioneer David Liu reported this week that they have advanced a promising therapeutic platform for delivering gene-editing proteins efficiently in vivo into a fourth generation. Based on a retrovirus scaffold they engineered into DNA-free virus-like particles (eVLPs), their platform can deliver genome-altering base editors to several mouse and human cells in multiple organs with minimal off-target toxic effects. And in a proof-of-principle demonstration, they reported the platform restored visual function in a mouse model of genetic blindness. Cell

AI could help navigate antibiotic resistance in hospitals

Researchers at ETH Zurich and the Swiss Institute of Bioinformatics in Lausanne, Switzerland, have paired machine learning with the common analytical technique of Matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) mass spectrometry (say that three times fast) in order to predict antimicrobial resistance. Training their AI on a library of hundreds of thousands of mass spectra and associated clinically identified markers of microbial resistance collected from four Swiss hospitals, they performed a retrospective case study of 63 patients and found that if they had implemented their algorithm, it would have altered the clinical treatment for nine of those people—benefiting eight of them. Nature Medicine

Exercise atlas shows how timing affects metabolism

Looking to reap the most reward from your workout? According to researchers at the German Center for Diabetes Research in Neuherberg, Germany, and the Karolinska Institute in Stockholm, Sweden, it’s not just how long you exercise that affects your results, but also what time of day you choose to exercise. They developed a comprehensive atlas providing insight into how exercise timing impacts tissue-specific and system-wide metabolic changes. To do this, the researchers examined and mapped changes in seven tissues and systemic metabolic responses among mice exercising at different times of day. The hope is that this novel atlas can provide insight into how exercise timing can be utilized to optimize metabolic outputs. Cell Metabolism

Healed rabbit knees hold promise for people with osteoarthritis

Scientists at the University of Connecticut have developed a biodegradable, piezoelectric device that converts the force of muscle movement during exercise into electrical charges that can stimulate nearby cartilage, helping it grow. In a proof-of-concept study, they showed that the device can accelerate the healing of damaged cartilage in the knees of rabbits. They suggest an implant based on their scaffold could help regenerate damaged cartilage in people with osteoarthritis or regenerate other damaged tissues. Science Translational Medicine

Down syndrome sheds light on aging and autoimmunity

Two papers this month shed light on dysregulated aging mechanisms caused by Down syndrome, the common congenital abnormality affecting 1 in 800 births. In the first study, appearing in Science Translational Medicine, researchers at Virginia Mason University studied age-related immune alterations in 28 people with Down syndrome, showing how the syndrome accelerated changes in their immune systems over time, leading to autoimmunity—work that may also inform our understanding of autoimmune diseases like type 1 diabetes. Researchers at MIT, in a second, unrelated study observed that the chromosomal abnormalities underlying Down syndrome disrupt neural progenitor cells similar to what is observed in aging senescent cells. They also found that a combination of the senolytic drug dasatinib and quercetin ameliorates these disruptions, suggesting a possible avenue for exploring future treatment for Down syndrome. Cell Stem Cell

Uninherited genetic causes of male infertility

Male infertility accounts for about half of all infertility cases but for 40 percent of infertile men, the cause remains unknown. A new study, however, suggests an underappreciated genetic mechanism could account for many of those cases. According to a research team at U.K.’s Newcastle University, parents don’t need to pass down mutated genes to their sons for infertility-causing mutations to occur. Some genetic mutations can occur spontaneously and de novo in early embryogenesis—meaning the mutations are not passed along but originate after the father’s sperm has fertilized the mother’s egg. In a global study, the researchers sequenced DNA from 185 infertile men and their parents. They identified 145 rare mutations that appear to contribute to infertility, 29 of which were found to be directly involved with sperm development. Nature Communications