When the ancestors of modern Eurasians migrated from Africa and interbred with the archaic humans of Eurasia, namely Neanderthals and Denisovans, the DNA of the archaic ancestors became anatomically integrated into the genomes of modern humans. homo sapiens. This process could accelerate adaptation to Eurasian environmental factors, such as reduced UV radiation and increased seasonal variation. In a new study, scientists from Vanderbilt University, the University of Pennsylvania, and the University of California, San Francisco have discovered lineage-specific genetic differences in circadian genes and their regulatory elements between humans and Neanderthals. They found that the introgressed genetic variants were enriched with effects on circadian regulation and consistently increased morningness tendencies in Europeans. The results expand our understanding of how the genomes of humans and our closest relatives responded to environments with different light-dark cycles.

All anatomically modern humans trace their origins to the African continent about 300,000 years ago, where environmental factors shaped many of their biological characteristics.

They arrived in Eurasia 70,000 years ago, but other humans, Neanderthals and Denisovans, lived there for more than 400,000 years.

These archaic humans diverged from anatomically modern humans about 700,000 years ago, and as a result, humans and archaic hominid ancestors evolved under different environmental conditions.

“Although there was considerable variation in the latitudinal range of each group, Eurasian hominids primarily lived at consistently high latitudes and were therefore exposed to larger amplitude seasonal fluctuations in photoperiod,” said the University of California. said the San Francisco school. Dr. John Capra and his colleagues.

“Given the influence of environmental cues on circadian biology, we hypothesized that these separate evolutionary histories produced differences in circadian traits adapted to different environments.”

Although previous studies have shown that many of the archaic ancestors of modern humans are not beneficial and have been removed by natural selection, some archaic hominin variants that remain in human populations has shown evidence of adaptation.

For example, archaic genetic variation is thought to be associated with differences in hemoglobin levels, immune resistance to new pathogens, levels of skin pigmentation, and fat composition among Tibetans at high altitudes.

Changes in patterns and levels of light exposure have biological and behavioral effects that lead to evolutionary adaptations.

Scientists have extensively studied the evolution of circadian adaptations in insects, plants, and fish, but humans have been less well studied.

The Eurasian environment where Neanderthals and Denisovans lived for hundreds of thousands of years is located at higher latitudes and has more variable daylight hours than where modern humans evolved before leaving Africa.

Dr. Capra and his co-authors therefore investigated whether there was genetic evidence for differences in circadian clocks between Neanderthals and modern humans.

Using a combination of literature searches and expert knowledge, they defined a set of 246 circadian genes.

They found hundreds of genetic variations unique to each strain that can affect genes involved in the circadian clock.

Using artificial intelligence techniques, they identified 28 circadian genes that contain mutations that could alter splicing in archaic humans and that may be differentially regulated between modern and archaic humans. identified 16 circadian genes.

This indicates that there may be functional differences between the circadian clocks of ancient and modern humans.

Eurasian modern humans and Neanderthal ancestors interbred, so some humans may have acquired circadian variation from Neanderthals.

To test this, researchers investigated whether introgressed genetic variants were associated with the body’s preferences for wakefulness and sleep in a large cohort of hundreds of thousands of people at UK Biobank. did.

They found a number of introgressed mutants that affected sleep preferences, and most surprisingly, they found that these mutants consistently increased morningness, or the tendency to rise early.

This suggests a directional influence on this trait and is consistent with adaptations to high latitudes observed in other animals.

Increased morning time in humans is associated with a shortened circadian clock period. This may be beneficial at high latitudes, as it has been shown that sleep and wakefulness can be coordinated more quickly with external timing cues.

Shortening of the circadian period is required to synchronize the long summer light period at high latitudes in Drosophila, and selection for a shorter circadian period results in a latitudinal shift with increasing latitude in natural Drosophila populations. There is a latitudinal gradient in which the period decreases.

Therefore, the bias toward morningness in introgressed mutants may indicate selection for shortened circadian periods in populations living at high latitudes.

The tendency to be a morning person may have been evolutionarily beneficial to our ancestors who lived in the high latitudes of Europe, and would have been a Neanderthal genetic trait worth preserving.

“By combining ancient DNA, extensive genetic studies in modern humans, and artificial intelligence, we discovered substantial genetic differences in the circadian systems of Neanderthals and modern humans,” Dr. Capra said. .

“And by analyzing fragments of Neanderthal DNA that remain in the genomes of modern humans, we discovered surprising trends, many of which influence the regulation of circadian genes in modern humans. These effects are primarily in the consistent direction of increasing Neanderthal tendencies.” Morning people. ”

“This change is consistent with the effects of living at high latitudes on animals’ circadian clocks, and changes in seasonal light patterns may allow them to adjust their circadian clocks more quickly. ”

“Our next steps include applying these analyzes to more diverse modern human populations and investigating the effects of the Neanderthal variants we identified on circadian clocks in model systems. and applying similar analyzes to other potentially adaptive traits.”

of the team paper It was published in the magazine Genome biology and evolution.

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Kayla Velasquez-Arsley other. 2023. Archaic genetic introgression shaped human circadian characteristics. Genome biology and evolution 15 (12): evad203; doi: 10.1093/gbe/evad203