Fire Usage and Ancient Hominin Detoxification Genes: Protective Ancestral Variants Dominate While Additional Derived Risk Variants Appear in Modern Humans

Abstract

Studies of the defence capacity of ancient hominins against toxic substances may contribute importantly to the reconstruction of their niche, including their diets and use of fire. Fire usage implies frequent exposure to hazardous compounds from smoke and heated food, known to affect general health and fertility, probably resulting in genetic selection for improved detoxification. To investigate whether such genetic selection occurred, we investigated the alleles in Neanderthals, Denisovans and modern humans at gene polymorphisms well-known to be relevant from modern human epidemiological studies of habitual tobacco smoke exposure and mechanistic evidence. We compared these with the alleles in chimpanzees and gorillas. Neanderthal and Denisovan hominins predominantly possess gene variants conferring increased resistance to these toxic compounds. Surprisingly, we observed the same in chimpanzees and gorillas, implying that less efficient variants are derived and mainly evolved in modern humans. Less efficient variants are observable from the first early Upper Palaeolithic hunter-gatherers onwards. While not clarifying the deep history of fire use, our results highlight the long-term stability of the genes under consideration despite major changes in the hominin dietary niche. Specifically for detoxification gene variants characterised as deleterious by epidemiological studies, our results confirm the predominantly recent appearance reported for deleterious human gene variants, suggesting substantial impact of recent human population history, including pre-Holocene expansions.

Bacteria in the ageing gut: did the taming of fire promote a long human lifespan?

“…There are not many examples of this type, however. To substantiate specific positive selection against smoke and cooked products, a study of the genomes of Neanderthals, Denisovans and modern human isolates at gene polymorphisms well‐known to be relevant to contact with tobacco smoke compared them with their counterparts in chimpanzees and gorillas (Aarts et al ., ).…”

“…The GST genes are upregulated in response to oxidative stress and are overexpressed in many tumours, which are, by definition, maintaining a young state of the cells (Allocati et al ., ). The majority of these enzymes had already the high efficient form in our ancestors (Aarts et al ., ).…”

Evolution of hominin detoxification: Neanderthal and modern human AHR respond similarly to TCDD

“…Fire afforded humans with (well-known) benefits affecting many domains of the human niche, including food preparation and diet, defense against predators, thermoregulation and social interaction (Carmody et al, 2009;Wiessner, 2014;Wrangham, 2009). However, pyrotechnology also came with (lesser known) costs (Henry et al, 2018), including toxicological ones (Aarts et al, 2016). The utilization of fire fueled with wood or other types of biomass on a daily basis by prehistoric hominins implied frequent exposure to toxic components of smoke, to which polycyclic aromatic hydrocarbons (PAHs) contribute importantly (Freeman et al, 1990).…”

“…. In an attempt to shed independent light on the debated chronology, Aarts et al (2016) hypothesized that frequent exposure to toxic compounds occurring in smoke would have resulted in genetic adaptations in genes involved in detoxification of these toxicants. They analyzed 36 genetic variants in a comprehensive set of 19 relevant genes in Neanderthal, Denisovan, and (pre)historic and extant anatomically modern human genomes.…”

“…Starting from an evolutionary hypothesis comparable to Aarts et al (2016), Hubbard et al (2016) focused on the aryl hydrocarbon receptor (AHR) gene, for which humans display a fixed difference (Val381) from the Neanderthal and Denisovan (Ala381) ancestral variant. Hubbard et al (2016) performed an analysis of the modern human versus the Neanderthal AHR in rat cells and concluded that the Neanderthal AHR induced CYP1A1 mRNA expression with an EC50 between 150-and 1000fold lower than observed with the human AHR.…”