Infectious Diseases

Big brains, farms and killer bugs: Epic tale of evolution still affecting us today

Woodcut of dying plague patients from 1532
Public domain, via Wikimedia Commons
Woodcut of dying plague patients from 1532
Public domain, via Wikimedia Commons

Humans have been getting infected by ancient bacteria and viruses for at least 37,000 years. Now, for the first time, pathogen DNA has uncovered a pivotal disease "turning point" that happened 6,500 years ago, during which our biology and society created a perfect storm that would forever change our evolutionary path.

Scientists from Curtin University in Australia and Denmark's University of Copenhagen have, for the first time, traced the evolutionary timeline of harmful microbes that infected ancient humans across Europe and Asia, in the process revealing a dramatic shift in disease risk that coincided with the emergence of farming animals.

Analyzing ancient DNA from 279 samples of human remains spanning a massive 37,000 years, the researchers identified dozens of pathogens – from ancient genetic fragments of bacteria, viruses and parasites – that once infected our ancestors. Many of these bugs – belonging to 58 genera – were also identified as the ancestors of microbes that still present a threat to us, including tapeworms, hepatitis B virus, salmonella and mycobacterium (tuberculosis).

"To create an archaeogenetic-based spatiotemporal map of human pathogens, we screened shotgun-sequencing data from 1,313 ancient humans covering 37,000 years of Eurasian history," the researchers wrote. "We demonstrate the widespread presence of ancient bacterial, viral and parasite DNA, identifying 5,486 individual hits against 492 species from 136 genera. Among those hits, 3,384 involve known human pathogens, many of which had not previously been identified in ancient human remains."

And here's where it gets interesting. We know that, looking at a timeline of infectious diseases, there was an explosion of diverse pathogens jumping from animals to humans around 6,500 years ago, reaching a peak around 1,500 years later. This coincided with the birth of agriculture and humans living in much closer proximity to animals, compared to the lifestyles of previous hunter-gatherer societies.

Domesticating animals like cows, pigs, sheep and chickens created the perfect setup for zoonotic pathogens (microbes originating in animals) to jump into humans. Many of our most devastating diseases – like tuberculosis, influenza and measles – likely began as animal infections. And we have plenty of recent examples of zoonotic outbreaks to show it's not just ancient history.

This farming age, as well as more densely populated communities and poor sanitary conditions saw these zoonotic pathogens evolve to better transmit among their new hosts, with no need to use animals as intermediaries anymore.

But there's another interesting factor the researchers address: By this time, humans had developed much larger brains than their ancestors, which facilitated more complex societies and rapid development. However, it also left us vulnerable to disease. Large brains are biologically expensive to run; they take up about 2% of our body mass but use 20% of our energy – at rest. In order to fuel such a costly organ, the researchers added, there was likely a trade-off with how our immune system functioned.

The researchers compared how human and chimpanzee immune cells reacted to a range of human-specific viruses and bacteria. Using genetically "humanized" mice, stem cell transplants and RNA sequencing, they found that the chimp immune systems respond faster and more strongly, while human cells had dialed-down reactions – especially in key infection-fighting genes.

This muted response may have helped protect our larger brains from damaging inflammation, but it also primed humans to be more susceptible to novel zoonotic pathogens from animals. While a peak in infections hit around 5,000 years ago, it doesn't mean there was a drop in humans being infected – the viruses, and our immune responses to many of them, changed.

Once humans had been exposed to many of the animal pathogens in their environment, there were fewer “new” ones left to make the jump to us. The most successful ones became endemic, constantly circulating among populations of humans. In the process, they evolved niche characteristics that made them specifically human bugs – like tuberculosis.

So despite present-day medical advances, humans are still uniquely vulnerable to some of the world’s most persistent and deadly diseases, which is a byproduct of our biological and social evolution.

"During the Holocene, human lifestyles changed significantly as agriculture, animal husbandry and pastoralism became key practices but the impact on infectious disease incidence is debated," the researchers wrote. "Our study represents a large-scale characterization of ancient pathogens across Eurasia, providing clear evidence that identifiable zoonotic pathogens emerged around 6,500 years ago and were consistently detected after 6,000 years ago. Although zoonotic cases probably existed before 6,500 years ago, the risk and extent of zoonotic transmission probably increased with the widespread adoption of husbandry practices and pastoralism. Today, zoonoses account for more than 60% of newly emerging infectious diseases."

This study is relevant to the present day because we're still dealing with the consequences of what our farming age unleashed, with those ancient pathogens still infecting millions today. Thanks to newly analyzed fragments of ancient bugs, the researchers have been able to present the most comprehensive picture of how agriculture changed human health forever, essentially establishing the conditions for infectious diseases that still plague us to this day.

And, until now, this "turning point" in human history – and the human-pathogen arm's race – hasn't been fully understood or documented, making it a fascinating new insight into evolutionary processes and how interconnected our species and other organisms are.

"Our findings demonstrate how the nascent field of genomic paleoepidemiology can create a map of the spatial and temporal distribution of diverse human pathogens over millennia," the researchers concluded. "This map will develop as more ancient specimens are investigated, as will our abilities to match their distribution with genetic, archaeological and environmental data. Our current map shows clear evidence that lifestyle changes in the Holocene led to an epidemiological transition, resulting in a greater burden of zoonotic infectious diseases. This transition profoundly affected human health and history throughout the millennia and continues to do so today."

The study was published in the journal Nature.

Source: Curtin University via Scimex

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