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The mutations that make us human

September, 2016

painting of Neandarthals with an open firepit

When we imagine what made early modern humans unique, it's tempting to imagine a caveperson, brandishing a lit torch against the night, using fire to eke out a better living from a hostile environment. However, humans were not alone in their use of fire. Neanderthals, which inhabited the planet at the same time as the first modern humans, were using fire at least 175,000 years ago, and there is evidence that Homo erectus used fire in Africa more than a million years ago. Now, new research suggests that part of what distinguished early humans from their close relatives was not their use of fire, but how the human lineage evolved in response to fire. This past summer, a group of biologists and anthropologists announced that they'd discovered a mutation that may have allowed our early ancestors to better deal with breathing in the toxic chemicals produced by open fires.

Where's the evolution?

new phylogenetic tree

How could we possibly know how our ancestors who roamed the earth hundreds of thousands of years ago handled smoke inhalation in comparison to their Neanderthal cousins? Just 30 years ago, we couldn't have. However, the relatively new field of ancient DNA studies makes it possible. Biologists used to think that DNA degrades quickly after the death of an organism – and most of it does. But in the 1980s, we discovered that in certain circumstances, a small amount of DNA is preserved. The oldest DNA sequences that scientists have yet recovered come from a 700,000-year-old horse. With the improvement of technology for isolating tiny fragments of DNA and figuring out how they can be puzzled together, biologists have now reconstructed the complete genome sequences for both Neanderthals and their close relatives, the Denisovans. In those strings of As, Ts, Gs, and Cs, lies a clue to how ancient humans dealt with fire: a gene called AHR, short for aryl hydrocarbon receptor.

All vertebrates have a version of the AHR gene. It encodes a protein that is present in the cytoplasm of cells. The AHR protein binds with some naturally occurring substances and with certain toxic substances that might enter the cell, like PCBs, dioxin, and polycyclic aromatic hydrocarbons (PAHs), which are produced by combustion (e.g., burning wood). When the AHR protein binds these toxic substances, it carries them into the nucleus of the cell and activates other genes. Through a chain of reactions, this can cause toxic effects and even death.

The AHR gene is known to evolve quickly. Biologists have discovered that in just 60 years, the AHR gene in one fish species (the Atlantic tomcod) has evolved in a way that allows the fish to resist many of the negative effects of PCB exposure. When most fish embryos are exposed to PCBs, they develop heart defects and other complications. But fish from the Hudson River population of Atlantic tomcod don't have this problem because of a mutated version of the AHR gene. This gene version spread through the fish population via natural selection over the last 60 years of exposure to high levels of PCBs.

And now recent research suggests that our ancestors may have experienced a similar process through exposure to wood smoke. Researchers in a toxicology laboratory identified a single amino acid change in the human version of the AHR protein that made it much worse at binding toxic substances than the mouse version of the protein. The human version had a valine as its 381st amino acid, and the mouse version had an alanine at this position. Curious how and why this difference might have arisen, the biologists investigated which gene versions were carried by our closest relatives. Interestingly, all of the six Neanderthal sequences available and the two Denisovan sequences had an alanine at position 381. In fact, all non-human primates seem to have a mouse-like version of this gene that generates an alanine at position 381. One the other hand, every single one of the thousands of modern human genomes sequenced produces a protein with a valine at this position. It seems that sometime after humans split from the lineage of the Neanderthals and Denisovans around 800,000 years ago, this mutation rose to a high frequency in the human lineage (while remaining rare or non-existent in their non-human relatives). The question is, why did that happen?

It's hard to know for certain why the mutant AHR gene spread through the early human population, but recent toxicological studies provide a tantalizing clue. In the laboratory, biologists investigated the two different versions of the AHR protein. Compared to the human version, the Neanderthal version much more readily bound chemicals found in smoke (i.e., PAHs) and much more readily turned on genes in DNA known to cause toxic effects. The human version of AHR seemed to resist binding toxic substances produced by fires, while still maintaining its normal function within the cell. This could protect humans from some of the harmful effects of excessive smoke inhalation, which include respiratory infections and poor outcomes during pregnancy. This evidence supports the hypothesis that, as early humans used fire for various purposes, natural selection favored individuals who carried the AHR mutation and so experienced fewer negative side effects from breathing in smoke.

While this a plausible explanation for how the mutant AHR gene spread through the early human population, it does not necessarily mean that this advantage allowed humans to outcompete their Neanderthal and Denisovan cousins. Biologists are exploring many different hypotheses about why Neanderthals and Denisovans went extinct but humans did not. Nevertheless, the available evidence is consistent with the idea that, among their relatives, humans were unique in evolving physiological adaptations that let them better cope with a smoky environment, while still allowing them to harness the benefits of fire — the light and heat that kept us warm, provided protection, and let us cook our food and make better tools.

Read more about it

Primary literature:

  • Hubbard, T. D., Murray, I. A., Bisson, W. H., Sullivan, A. P., Sebastian, A., Perry, G., H., ...Perdew, G. H. (2016). Divergent Ah receptor ligand selectivity during Hominin evolution. Molecular Biology and Evolution. DOI 10.1093. read it
News articles:

Understanding Evolution resources:

Discussion and extension questions

  1. What information did scientists get from ancient DNA studies that led to the hypothesis that a mutant AHR gene version was favored in early human populations?
  2. What other evidence (besides ancient DNA) supports the idea that a mutant AHR gene version was favored in early human populations?
  3. Read this description of the concept of evolutionary fitness. What fitness advantage might ancient humans with the mutant version of AHR have had over ancient humans with the ancestral version of AHR?
  4. Review the process of natural selection. Use the four steps described on that page to explain how the mutant AHR gene might have spread through early human populations.
  5. Advanced: The research described here suggests that ancient humans’ use of fire favored individuals carrying a mutant AHR gene. Describe a few possible explanations for why the available Neanderthal sequences (which came from another fire-using lineage) did not have the mutant AHR gene.
Related lessons and teaching resources

  • Teach about AHR evolution in the Atlantic Tomcod: This news brief for grades 9-16 examines the genetic basis for the evolution of resistance to PCBs in the Hudson River tomcod. Though this is great for the tomcod, what might it mean for other organisms in the ecosystem?
  • Teach about the spread of mutations in human populations: In this case study from DNA to Darwin, college students investigate the origin and action of mutations that are thought to have arisen in human populations in response to selection pressure from malaria.
  • Teach about physiological adaptations in humans: In Adaptation to Altitude, a set of sequenced lessons from the Smithsonian, high school and college students learn how to devise an experiment to test the difference between acclimation and adaptation; investigate how scientific arguments show support for natural selection in Tibetans; design an investigation using a simulation based on the Hardy-Weinberg principle to explore mechanisms of evolution; and devise a test for whether other groups of people have adapted to living at high altitudes.

References

  • Hubbard, T. D., Murray, I. A., Bisson, W. H., Sullivan, A. P., Sebastian, A., Perry, G., H., ...Perdew, G. H. (2016). Divergent Ah receptor ligand selectivity during Hominin evolution. Molecular Biology and Evolution. DOI 10.1093.
  • James, S. R. (1989). Hominid use of fire in the Lower and Middle Pleistocene: a review of the evidence. Current Anthropology. 30: 1-26.
  • Jaubert, J., Verheyden, S., Genty, D., Soulier, M., Cheng, H., Blamert, D., ... Santos, F. (2016). Early Neanderthal constructions deep in Bruniquel Cave in southwestern France. Nature. 534: 111-114.
  • Orlando, L., Ginolhac, A., Zhang, G., Froese, D., Albrechtsen, A., Stiller, M., ... Willerslev, E. (2013). Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse. Nature. 499: 74-78.