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Genetic Linkage

Were Ancient Humans Healthier Than Us?

A curious thing happened when researchers at Georgia Tech used modern human genome sequences to look back at the possible health of our long-ago ancestors – they found that while the Neanderthals and Denisovans of 30,000 to 50,000 years ago seemed to have been genetically sicker than us, “recent ancients” from a few thousand years ago may actually have been healthier. Their paper, “The Genomic Health of Ancient Hominins,” is published in Human Biology.

How could that be? Perhaps drugs and procedures that enable us to live with certain conditions also perpetuate gene variants that would otherwise sicken us enough to not reproduce. We pass on those genes and inexorably weaken our global gene pool.

A cheetah with hereditary visual impairment would be weeded out, outrun and not likely to leave offspring. But we humans just use corrective lenses and have kids.

PROBING ANCIENT GENOMES

We’ve come a long way from imagining what life must have been like for ancient humans from just rare teeth and bits of bone. Now sequenced genomes from a sliver of a Denisovan pinkie, from Neanderthal skeletons, and from several sampled tissues of Ötzi the Tyrolean ice man, offer glimpses of past health. Had arrows and wounds not done in Ötzi 5300 years ago, his inherited heart disease might have. He also had brown eyes and type O blood, and would have been lactose intolerant if he’d eaten dairy. Lactose intolerance is the wild type ancestral condition, which didn’t begin to be selected against until adults started consuming nonhuman milk products and suffering cramps.

Joe Lachance, Ali J. Berens, and Taylor L. Cooper of Georgia Tech started out with 449 genome sequences from individuals who’d lived at various times from 430 to 50,000 years ago. The trio compared the ancient genome sequences to a compendium of 3,180 gene variants associated with specific diseases today, ignoring trivial traits and genes carried on the X or Y chromosome. Then they selected the 147 genomes that had more than 50% of the risk gene variants to further analyze. They focused mostly on individuals who lived 2,000 to 9,000 years ago, and categorized each as from a hunter-gatherer, a farmer, or a pastoralist (someone who raises sheep or cattle).

A similar study, one of my favorites, compared Neanderthal DNA sequences to electronic health records from 28,000 modern Europeans. It added to the list of predispositions that Neanderthals might have faced: depression, skin lesions, urinary tract infections, and tobacco addiction.

QUANTIFYING DISEASE RISK

The Georgia Tech researchers used an overall genetic risk score (GRS) as well as 9 specific disease categories.

The GRS included all 3,180 gene variants weighted for the magnitude of their effects. In determining cholesterol level in the blood, for example, some gene variants have enormous effects, such as the mutation that causes familial hypercholesterolemia, and others not so much. The GRS paints a portrait of risk, not necessarily actual diseases.

A high GRS is bad. A value of 82, for example, means the person would have been at greater risk to get sick from risk genes than 82% of modern humans. “How this percentile maps to actual disease risks is likely to be trait-specific. For example, you might only be high risk for a disease if you are above the 90th percentile (think of a liability threshold), with only minimal differences in risk between individuals who are at the 25th and 50th percentiles,” said Dr. Lachance.

The 9 disease categories were allergy/autoimmune, cancer, cardiovascular disease, dental/periodontal, gastrointestinal/liver, metabolic/weight, miscellaneous, morphological/muscle, and neurological/psychological.

The analysis revealed several apparent trends:

• Pastoralists had “extremely healthy genomes” for allergy/autoimmunity, cancer, gastrointestinal ills, and dental health. Farmers and hunter-gatherers were less healthy but about even. Dr. Lachance can’t explain this finding, but suggests that the better health of those who work with cattle and sheep may have been due to exposure to different environments, perhaps like today farm kids have fewer allergies than kids raised in cities.

• Ancient people who lived in the north were healthier. They had better teeth and less cancer.

• The most ancient individuals were less likely to have been predisposed to cancer and neurological/psychological conditions. Maybe they didn’t live long enough to develop cancer or neurological disorders, and therapist records from thousands of years ago are scarce.

• Farmers had the worst teeth. Was it due to the residents of the dental plaque microbiome that formed in response to mashing all those new carbs from grains?

A particularly decrepit specimen was the famed Altai Neanderthal, who lived 50,000 to 100,000 years ago in the Altai mountains of Siberia. Her genome indicates that her parents were siblings, which must have been common when humanity struggled to survive in isolated caves. She had “poor genomic health” and a GRS of a whopping 97%, with genetic signposts of cancer, digestive and metabolic issues, muscle problems, and immune problems. But she had lower risk of cardiovascular disease.

The new work also fleshes out Ötzi: he had gastrointestinal problems and was prone to infection, but was neurologically intact.

A huge caveat to the study is the use of modern genomes as a point of comparison, which was necessary because ancient ones tend to be fragmented in different places. But incomplete evidence was a challenge even when all we had was fossil evidence. Remember the old view of Neanderthals as brown-haired brutes? Thanks to DNA analysis we now know that some of them were redheads.

ALTERNATIVE HYPOTHESES

The range of genetic risk scores among ancient and modern genomes is about the same, but overall genomic health seems to have improved. That could be due to context.

“It’s important to consider how well an individual’s genome is suited for the present environment,” Dr. Lachance told me, like the effects of a dairy diet on whether or not lactose intolerance becomes noticeable enough to affect reproduction, the currency of evolution. Imagine using a time machine to send someone today back to the distant past, where vision goes uncorrected, influenza is deadly, and tendency to bleed too easily or not fast enough is life-threatening. Gene function always filters through the lens of the environment.

Maybe the blame can’t be placed on our treating diseases that have genetic components to explain why recent ancients may have been healthier. Study design may be a simpler explanation for why the genomes from people who lived a few thousand years ago have a median GRS below 50%, and were therefore seemingly healthier than us. The study looked only at those above 50% – 302 of the 449 ancient genomes fell below that mark.

Consider this: Gene variants that elevated risks of certain diseases, or mutations that actually caused them, might have been stripped from the ancient populations as affected people were too sick to have children, so they wouldn’t even be in the modern genomes to which the older ones were compared. And the healthy pastoralists might have been a sampling error – they contributed only 19 of the 147 genomes.

Dr. Lachance thinks the second possibility – inability to compare full genomes from thousands of years ago to modern ones – the more likely explanation. The truth is out there, but it’ll take more experiments and data to illuminate it.

This post first appeared at the DNA Science blog at Public Library of Science here.






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