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A Scientific First: Early Biological Connections Between Neanderthals and

Homo sapiens

Global Breakthrough in a Prehistoric Cave in Israel:

Earliest evidence discovered of interbreeding between Homo sapiens and Neanderthals

The skeleton belongs to a five-year-old child who lived 140,000 years ago

Research team: “This discovery reveals the world’s earliest known human fossil showing morphological traits of both of these human groups, which until recently were considered two separate human species. The current study shows that the five-year-old child’s skeleton is the result of continuous genetic infiltration from the local—and older—Neanderthal population into the Homo sapiens population.”

An international study led by researchers from Tel Aviv University and the French National Centre for Scientific Research provides the first scientific evidence that Neanderthals and Homo sapiens had biological and social relations, and even interbred for the first time, in the Land of Israel. The research team found a combination of Neanderthal and Homo sapiens traits in the skeleton of a five-year-old child discovered about 90 years ago in the Skhul Cave on Mount Carmel. The fossil, estimated to be about 140,000 years old, is the earliest human fossil in the world to display morphological features of both of these human groups, which until recently were considered two separate species. The study was led by Prof. Israel Hershkovitz of the Gray Faculty of Medical and Health Sciences at Tel Aviv University and Anne Dambricourt-Malassé of the French National Centre for Scientific Research. The findings of this historic discovery were published in the journal l’Anthropologie .

Research Video

“Genetic studies over the past decade have shown that these two groups exchanged genes,” explains Prof. Hershkovitz. “Even today, 40,000 years after the last Neanderthals disappeared, part of our genome—2 to 6 percent—is of Neanderthal origin. But these gene exchanges took place much later, between 60,000 to 40,000 years ago. Here, we are dealing with a human fossil that is 140,000 years old. In our study, we show that the child’s skull, which in its overall shape resembles that of Homo sapiens—especially in the curvature of the skull vault—has an intracranial blood supply system, a lower jaw, and an inner ear structure typical of Neanderthals.”

For years, Neanderthals were thought to be a group that evolved in Europe, migrating to the Land of Israel only about 70,000 years ago, following the advance of European glaciers. In a groundbreaking 2021 study published in the prestigious journal Science, Prof. Hershkovitz and his colleagues showed that early Neanderthals lived in the Land of Israel as early as 400,000 years ago. This human type, which Prof. Hershkovitz called “Nesher Ramla Homo” (after the archaeological site near the Nesher Ramla factory where it was found), encountered Homo sapiens groups that began leaving Africa about 200,000 years ago—and, according to the current study’s findings, interbred with them. The child from the Skhul Cave is the earliest fossil evidence in the world of the social and biological ties forged between these two populations over thousands of years. The local Neanderthals eventually disappeared when they were absorbed into the Homo sapiens population, much like the later European Neanderthals.

The researchers reached these conclusions after conducting a series of advanced tests on the fossil. First, they scanned the skull and jaw using micro-CT technology at the Shmunis Family Anthropology Institute at Tel Aviv University, creating an accurate three-dimensional model from the scans. This enabled them to perform a complex morphological analysis of the anatomical structures (including non-visible structures such as the inner ear) and compare them to various hominid populations. To study the structure of the blood vessels surrounding the brain, they also created an accurate 3D reconstruction of the inside of the skull.

“The fossil we studied is the earliest known physical evidence of mating between Neanderthals and Homo sapiens,” says Prof. Hershkovitz. “In 1998, a skeleton of a child was discovered in Portugal that showed traits of both of these human groups. But that skeleton, nicknamed the ‘Lapedo Valley Child,’ dates back to 28,000 years ago—more than 100,000 years after the Skhul child. Traditionally, anthropologists have attributed the fossils discovered in the Skhul Cave, along with fossils from the Qafzeh Cave near Nazareth, to an early group of Homo sapiens. The current study reveals that at least some of the fossils from the Skhul Cave are the result of continuous genetic infiltration from the local—and older—Neanderthal population into the Homo sapiens population.”

Link to the article:

https://www.sciencedirect.com/science/article/pii/S0003552125000366?via%3Dihub

New genetic research suggests that hibernating animals’ superpowers could lie hidden in our own DNA.

Animals that hibernate are incredibly resilient. They can spend months without food or water, muscles refusing to atrophy, body temperature dropping to near freezing as their metabolism and brain activity slow to a crawl. When they emerge from hibernation, they recover from dangerous health changes similar to those seen in type 2 diabetes, Alzheimer’s disease, and stroke.

The new research provides clues on how to unlock these hibernating superpowers, opening the door to someday developing treatments that could reverse neurodegeneration and diabetes.

Two studies describing the results are published in Science (one, two).

Metabolism and obesity

A gene cluster called the “fat mass and obesity (FTO) locus” plays an important role in hibernators’ abilities, the researchers found. Intriguingly, humans have these genes too.

“What’s striking about this region is that it is the strongest genetic risk factor for human obesity,” says Chris Gregg, professor in neurobiology and human genetics at University of Utah Health and senior author on the studies. But hibernators seem able to use genes in the FTO locus in new ways to their advantage.

The team identified hibernator-specific DNA regions that are near the FTO locus and that regulate the activity of neighboring genes, tuning them up or down. The researchers speculate that adjusting the activity of neighboring genes, including those in or near the FTO locus, allows hibernators to pack on the pounds before settling in for the winter, then slowly use their fat reserves for energy throughout hibernation.

Indeed, the hibernator-specific regulatory regions outside of the FTO locus seem crucial for tweaking metabolism. When the researchers mutated those hibernator-specific regions in mice, they saw changes in the mice’s weight and metabolism. Some mutations sped up or slowed down weight gain under specific dietary conditions; others affected the ability to recover body temperature after a hibernation-like state or tuned overall metabolic rate up or down.

Intriguingly, the hibernator-specific DNA regions the researchers identified weren’t genes themselves. Instead, the regions were DNA sequences that contact nearby genes and turn their expression up or down, like an orchestra conductor fine-tuning the volume of many musicians. This means that mutating a single hibernator-specific region has wide-ranging effects extending far beyond the FTO locus, explains Susan Steinwand, research scientist in neurobiology at U of U Health and first author on one of the studies.

“When you knock out one of these elements—this one tiny, seemingly insignificant DNA region—the activity of hundreds of genes changes,” she says. “It’s pretty amazing.”

Understanding hibernators’ metabolic flexibility could lead to better treatments for human metabolic disorders like type 2 diabetes, the researchers say.

“If we could regulate our genes a bit more like hibernators, maybe we could overcome type 2 diabetes the same way that a hibernator returns from hibernation back to a normal metabolic state,” says Elliott Ferris, bioinformatician at U of U Health and first author on the other study.

Needles in a haystack

Finding the genetic regions that may enable hibernation is a problem akin to excavating needles from a massive DNA haystack. To narrow down the regions involved, the researchers used multiple independent whole-genome technologies to ask which regions might be relevant for hibernation. Then, they started looking for overlap between the results from each technique.

First, they looked for sequences of DNA that most mammals share but that had recently changed in hibernators.

“If a region doesn’t change much from species to species for over 100 million years but then changes rapidly and dramatically in two hibernating mammals, then we think it points us to something that is important for hibernation, specifically,” Ferris says.

To understand the biological processes that underlie hibernation, the researchers tested for and identified genes that turn up or down during fasting in mice, which triggers metabolic changes similar to hibernation. Next, they found the genes that act as central coordinators, or “hubs,” of these fasting-induced changes to gene activity.

Many of the DNA regions that had recently changed in hibernators also appeared to interact with these central coordinating hub genes. Because of this, the researchers expect that the evolution of hibernation requires specific changes to the controls of the hub genes. These controls comprise a shortlist of DNA elements that are avenues for future investigation.

What about humans?

Most of the hibernator-associated changes in the genome appeared to “break” the function of specific pieces of DNA, rather than confer a new function. This hints that hibernators may have lost constraints that would otherwise prevent extreme flexibility in the ability to control metabolism. In other words, it’s possible that the human “thermostat” is locked to a narrow range of continuous energy consumption. For hibernators, that lock may be gone.

Hibernators can reverse neurodegeneration, avoid muscle atrophy, stay healthy despite massive weight fluctuations, and show improved aging and longevity. The researchers think their findings show that humans may already have the needed genetic code to have similar hibernator-like superpowers—if we can bypass some of our metabolic switches.

“Humans already have the genetic framework,” Steinwand says. “We just need to identify the control switches for these hibernator traits.” By learning how, researchers could help confer similar resilience to humans.

“There’s potentially an opportunity—by understanding these hibernation-linked mechanisms in the genome—to find strategies to intervene and help with age-related diseases,” Gregg says. “If that’s hidden in the genome that we’ve already got, we could learn from hibernators to improve our own health.”

Support for the research came from the National Institutes of Health, also including the National Institute on Aging , the National Institute of Mental Health, the National Library of Medicine. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of interest statement: Chris Gregg is a cofounder, consultant, and/or has financial interests in Storyline Health Inc., DepoIQ Inc., Primordial AI Inc., and Rubicon AI Inc.; Elliott Ferris is a consultant with financial interests in Primordial AI Inc.; Jared Emery is an employee with financial interests in Storyline Health Inc.

Source: University of Utah