Could a genetic mutation (or allele) that puts populations
at risk for illnesses in one environmental setting manifest itself in
positive ways in a different setting?
That's the question behind a recent paper published in The FASEB Journal
by several researchers including lead author Ben Trumble, an assistant professor at Arizona State University's School of Human Evolution and Social Change and ASU's Center for Evolution and Medicine.
‘The ApoE4 variant carriers up to a four-fold higher risk for Alzheimer's disease and other age-related cognitive declines, as well as a higher risk for cardiovascular disease.’
These researchers examined how the apolipoprotein E (ApoE) gene
might function differently in an infectious environment than in the
urban industrialized settings where ApoE has mostly been examined. All
ApoE proteins help mediate cholesterol metabolism, and assist in the
crucial activity of transporting fatty acids to the brain. But in
industrialized societies, ApoE4 variant carriers also face up to a
four-fold higher risk for Alzheimer's disease and other age-related
cognitive declines, as well as a higher risk for cardiovascular disease.
The goal of this study, Trumble explains, was to reexamine the
potentially detrimental effects of the globally-present ApoE4 allele in
environmental conditions more typical of those experienced throughout
our species' existence - in this case, a community of Amazonian
forager-horticulturalists called the Tsimane.
"For 99% of human evolution, we lived as hunter gatherers in small
bands and the last 5,000-10,000 years - with plant and animal
domestication and sedentary urban industrial life - is completely
novel," Trumble says. "I can drive to a fast-food restaurant to 'hunt
and gather' 20,000 calories in a few minutes or go to the hospital if
I'm sick, but this was not the case throughout most of human evolution."
Due to the tropical environment and a lack of sanitation, running
water, or electricity, remote populations like the Tsimane face high
exposure to parasites and pathogens, which cause their own damage to
cognitive abilities when untreated.
As a result, one might expect Tsimane ApoE4 carriers who also have a
high parasite burden to experience faster and more severe mental
decline in the presence of both these genetic and environmental risk
But when the Tsimane Health and Life History Project tested these
individuals using a seven-part cognitive assessment and a medical exam,
they discovered the exact opposite.
In fact, Tsimane who both carried ApoE4 and had a high parasitic
burden displayed steadier or even improved cognitive function in the
assessment versus non-carriers with a similar level of parasitic
exposure. The researchers controlled for other potential confounders
like age and schooling, but the effect still remained strong. This
indicated that the allele potentially played a role in maintaining
cognitive function even when exposed to environmental-based health
For Tsimane ApoE4 carriers without high parasite burdens, the rates
of cognitive decline were more similar to those seen in industrialized
societies, where ApoE4 reduces cognitive performance.
"It seems that some of the very genetic mutations that help us
succeed in more hazardous time periods and environments may actually
become mismatched in our relatively safe and sterile post-industrial
lifestyles," Trumble explains.
Still, the ApoE4 variant appears to be much more than an
evolutionary leftover gone bad, he adds. For example, several studies
have shown potential benefits of ApoE4 in early childhood development,
and ApoE4 has also been shown to eliminate some infections like giardia
"Alleles with harmful effects may remain in a population if such
harm occurs late in life, and more so if those same alleles have other
positive effects," adds co-author Michael Gurven, professor of
anthropology at University of California, Santa Barbara. "Exploring the
effects of genes associated with chronic disease, such as ApoE4, in a
broader range of environments under more infectious conditions is likely
to provide much-needed insight into why such 'bad genes' persist."
The abstract and full research paper "Apolipoprotein E4 is
associated with improved cognitive function in Amazonian
forager-horticulturalists with a high parasite burden" can be viewed here in The FASEB Journal