When the ancestors of modern Eurasians migrated out of Africa and interbred with Eurasian archaic hominins, namely Neanderthals and Denisovans, DNA of archaic ancestry integrated into the genomes of anatomically modern Homo sapiens. This process potentially accelerated adaptation to Eurasian environmental factors, including reduced ultra-violet radiation and increased variation in seasonal dynamics. In new research, scientists from Vanderbilt University, the University of Pennsylvania and the University of California, San Francisco discovered lineage-specific genetic differences in circadian genes and their regulatory elements between humans and Neanderthals. They found that introgressed gene variants are enriched for effects on circadian regulation, consistently increase propensity for morningness 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.
Velazquez-Arcelay et al. found that genetic material from Neanderthal ancestors may have contributed to the propensity of some people today to be early risers, the sort of people who are more comfortable getting up and going to bed earlier. Image credit: Holger Neumann / Neanderthal Museum.
All anatomically modern humans trace their origin to the African continent around 300,000 years ago, where environmental factors shaped many of their biological features.
Although they arrived in Eurasia 70,000 years ago, other hominins — Neanderthals and Denisovans — lived there for more than 400,000 years.
These archaic hominins diverged from anatomically modern humans around 700,000 years ago, and, as a result, the ancestors of humans and archaic hominins evolved under different environmental conditions.
“While there was substantial variation in the latitudinal ranges of each group, the Eurasian hominins largely lived at consistently higher latitudes and, thus, were exposed to higher amplitude seasonal variation in photoperiods,” said University of California, San Francisco’s 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 the distinct environments.”
Previous work has demonstrated that much of the archaic hominin ancestry in modern humans was not beneficial and removed by natural selection, but some of the archaic hominin variants remaining in human populations show evidence of adaptation.
For example, archaic genetic variants have been associated with differences in hemoglobin levels at higher altitude in Tibetans, immune resistance to new pathogens, levels of skin pigmentation, and fat composition.
Changes in the pattern and level of light exposure have biological and behavioral consequences that can lead to evolutionary adaptations.
Scientists have previously explored the evolution of circadian adaptation in insects, plants, and fishes extensively, but it is not well studied in humans.
The Eurasian environments where Neanderthals and Denisovans lived for several hundred thousand years are located at higher latitudes with more variable daylight times than the landscape where modern humans evolved before leaving Africa.
Thus, Dr. Capra and co-authors explored whether there was genetic evidence for differences in the circadian clocks of Neanderthals and modern humans.
They defined a set of 246 circadian genes through a combination of literature search and expert knowledge.
They found hundreds of genetic variants specific to each lineage with the potential to influence genes involved in the circadian clock.
Using artificial intelligence methods, they highlighted 28 circadian genes containing variants with potential to alter splicing in archaic humans and 16 circadian genes likely divergently regulated between present-day humans and archaic hominins.
This indicated that there were likely functional differences between in the circadian clocks in archaic hominins and modern humans.
Since the ancestors of Eurasian modern humans and Neanderthals interbred, it was thus possible that some humans could have obtained circadian variants from Neanderthals.
To test this, the researchers explored whether introgressed genetic variants have associations with the preferences of the body for wakefulness and sleep in large cohort of several hundred thousand people from the UK Biobank.
They found many introgressed variants with effects on sleep preference, and most strikingly, they found that these variants consistently increase morningness, the propensity to wake up early.
This suggests a directional effect on the trait and is consistent with adaptations to high latitude observed in other animals.
Increased morningness in humans is associated with a shortened period of the circadian clock. This is likely beneficial at higher latitudes, because it has been shown to enable faster alignment of sleep/wake with external timing cues.
Shortened circadian periods are required for synchronization to the extended summer light periods of high latitudes in fruit flies, and selection for shorter circadian periods has resulted in latitudinal clines of decreasing period with increasing latitude in natural fruit fly populations.
Therefore, the bias toward morningness in introgressed variants may indicate selection toward shortened circadian period in the populations living at high latitudes.
The propensity to be a morning person could have been evolutionarily beneficial for our ancestors living in higher latitudes in Europe and thus would have been a Neanderthal genetic characteristic worth preserving.
“By combining ancient DNA, large-scale 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.
“Then by analyzing the bits of Neanderthal DNA that remain in modern human genomes we discovered a striking trend: many of them have effects on the control of circadian genes in modern humans and these effects are predominantly in a consistent direction of increasing propensity to be a morning person.”
“This change is consistent with the effects of living at higher latitudes on the circadian clocks of animals and likely enables more rapid alignment of the circadian clock with changing seasonal light patterns.”
“Our next steps include applying these analyses to more diverse modern human populations, exploring the effects of the Neanderthal variants we identified on the circadian clock in model systems, and applying similar analyses to other potentially adaptive traits.”
The team’s paper was published in the journal Genome Biology and Evolution.
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Keila Velazquez-Arcelay et al. 2023. Archaic Introgression Shaped Human Circadian Traits. Genome Biology and Evolution 15 (12): evad203; doi: 10.1093/gbe/evad203
