An Ancient Evolutionary Advantage?

Shared sequences within the brain lipid-metabolism pathway between Neanderthals and modern Europeans highlight questions about how these genetic similarities arose.

By Emily Willingham | April 1, 2014

WIKIMEDIA, MATT CELESKY, DRMIKEBAXTERModern humans of European descent have a lot in common with their Neanderthal ancestors when it comes to genes related to fat breakdown in the brain. A team led by investigators from the Chinese Academy of Sciences in Shanghai has found that people of European descent have three times the number of Neanderthal-like sequences in such genes compared to other modern human populations examined. The results, published today (April 1) in Nature Communications, point to how studying ancestral sequences could help researchers better understand modern humans.

“This paper presents a sort of second-phase research using what we know about where genes have come from,” said John Hawks, a paleoanthropologist at the University of Wisconsin, Madison, who was not involved in the study. “For some that come from Neanderthals, we can use that information to learn something new about human genetics and human biology.”

To unravel whether genetics might influence how fat is broken down in the brain, the Russian Academy of Sciences’ Ekaterina Khrameeva and her colleagues compared gene sequence similarities among today’s Europeans, Asians, and Neanderthals relative to those from modern people of African descent. Previous studies have looked for patterns across genomes, but this group homed in on gene groups associated with metabolism, cancer, the immune system, and lipid breakdown, among others.

Lipid breakdown-associated gene variants signaled loudly through the genetic noise, showing far more sequence similarities between Europeans and Neanderthals than other comparisons. So the researchers profiled fat concentrations in the brains of modern humans of European, East Asian, and African descent, plus took measures in chimpanzee brains, comparing these results with gene-expression readouts from each group. They found parallels between the presence of Neanderthal-related gene variants and lipid profiles in the European brains, which the other modern human populations and chimpanzees did not share.

Another comparison reinforced the modern European-Neanderthal link. “We simply checked whether genetic variants shared between Neanderthals and Europeans in lipid catabolism genes are also shared with Denisovan,” said study coauthor Michael Lachmann, a theoretical evolutionary biologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. The Denisovans were an archaic human species who overlapped in time with Neanderthals and Homo sapiens and whose range included most of Asia.

“We don’t see the same alleles in the Denisovans,” said Lachmann in an e-mail. “This indicates that adaptive selection might have been restricted to Europe.”

But the biogeography is fuzzy. “When we say that lipid catabolism was affected by Neanderthal ancestry in Europeans but not in Asians, we really do not know at the moment where to put the geographical boundary of this effect,” he noted.

And what drove the adaptive selection for these lipid metabolism-associated gene variants remains unknown. “At this point, we cannot directly link these changes and environmental effects,” Lachmann said. He added that the human brain exists in state of “relatively constant” metabolic inputs and outputs, so what happens in the head isn’t simply a matter of direct influence from external factors.

Hawks agreed. “With this set of genes, they’ve shown that selection favored them relative to the rest of the things we got from Neanderthals,” he said. “But that doesn’t tell us why.”

The shared sequences also don’t explain how the variants ended up in modern Europeans. Was it through interspecies engagement, or simply through genetic artifacts both species retained from a shared ancestor?

In their paper, Khrameeva and her colleagues noted that speculation regarding some Neanderthal-H. sapiens gene flow through sexual reproduction is “appealing.” And experts in the field generally agree that the idea is plausible, even if it’s not their favored explanation.

“I would contend that it is most likely due to shared common ancestry,” Robert Lowery, a phylogeneticist at Indian River State College in Fort Pierce, Florida, told The Scientist in an e-mail. “Introgression from Neanderthals to humans—and much more likely, from modern humans to Neanderthals—is still a possibility.” Lowery was not involved in the work.

Hawks also acknowledged the introgression possibility and calls it the “much simpler” explanation.  But, he said, “Neanderthals are ancient relative to us, and maybe these things just show up because they’re ancient, not because we specifically got these from Neanderthals.”

E.E. Khrameeva et al., “Neanderthal ancestry drives evolution of lipid catabolism in contemporary Europeans,” Nature Communications, doi: 10.1038/ncomms4584, 2014.

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Avatar of: dr.mp.mph


Posts: 23

April 2, 2014

"An Ancient Evolutionary Advantage?" A rather sensationalist title for what the article covers. Besides that, it is an interesting article. I am now curious about which European populations the researchers sampled. Did they sample western Asians as well? Should they examine Northern and Southern Indians?
Avatar of: Hugh-F-61


Posts: 75

April 2, 2014

Assuming that this isn't a weency bit of contamination by European DNA, could lipid metabolism be associated with conditions being cold in Europe at the time? And if these genes (they mean alleles) are an advantage, why do they only have a frequency of 30%? When allele frequencies drift around like this for long periods it usually means they are selectively neutral. Why haven't they become fixed (frequency ~= 100%) so everyone benefits? The same applies to an earlier paper saying Neanderthal DNA in non-Africans was enriched for keratin genes. I will feel more convinced when someone can say clearly that a change from one (human origin) base to another base derived from Neanderthals at position N in gene X causes this specific advantageous effect.

Avatar of: James V. Kohl

James V. Kohl

Posts: 516

April 3, 2014

Excerpt: "... what drove the adaptive selection for these lipid metabolism-associated gene variants remains unknown. “At this point, we cannot directly link these changes and environmental effects,” Lachmann said. He added that the human brain exists in state of “relatively constant” metabolic inputs and outputs, so what happens in the head isn’t simply a matter of direct influence from external factors."

My comment: Food odors and pheromones directly link the epigenetic landscape to the physical landscape of DNA in the organized genomes of all species. What happens in the head is clearly nutrient-dependent and pheromone-controlled because it is a manifestation of ecological, social, neurogenic, and socio-cognitive niche construction. For example, nutrient-dependent single nucleotide polymorphisms and amino acid substitutions differentiate cell types in individuals of all species.

Pheromones control the physiology of nutrient-dependent reproduction, which is epigenetically-effected by nutrient stress and social stress during brain development. See for example: Mosaic Copy Number Variation in Human Neurons. " One straightforward hypothesis is that neurons with different genomes will have distinct molecular phenotypes because of altered transcriptional or epigenetic landscapes."

That hypothesis, which I have modeled, is more fully supported by other works co-authored by Philipp Khaitovich, the senior author of this paper reviewed by

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