Some of the same mutations allowing humans to
fend off deadly infections also make us more prone to certain inflammatory and
autoimmune diseases, such as Crohn's disease. Researchers describe how
ancestral origins impact the likelihood that people of African or Eurasian
descent might develop immune-related diseases. The authors also share evidence
that the human immune system is still evolving.
"In the past, people's lifespans were
much shorter, so some of these inflammatory and autoimmune diseases that can
appear in the second half of life were not so relevant," says first author
Jorge Dominguez-Andres (@dominjor), a postdoctoral researcher at Radboud
Institute for Molecular Life Science in the Netherlands. "Now that we live
so much longer, we can see the consequences of infections that happened to our
ancestors."
One of the body's best defenses against
infectious diseases is inflammation. Dominguez-Andres and senior author Mihai
Netea, a Radboud University immunologist and evolutionary biologist, compiled
data from genetics, immunology, microbiology, and virology studies and
identified how the DNA from people within different communities commonly
infected with bacterial or viral diseases was altered, subsequently allowing
for inflammation. While these changes made it more difficult for certain
pathogens to infect these communities, they were also associated with the
emergence -- over time -- of new inflammatory diseases such as Crohn's disease,
Lupus, and inflammatory bowel disease.
"There seems to be a balance. Humans
evolve to build defenses against diseases, but we are not able to stop disease
from happening, so the benefit we obtain on one hand also makes us more
sensitive to new diseases on the other hand," says Dominguez-Andres.
"Today, we are suffering or benefiting from defenses built into our DNA by
our ancestors' immune systems fighting off infections or growing accustomed to
new lifestyles."
For example, the malaria parasite Plasmodium
sp. has infected African populations for millions of years. Because of this,
evolutionary processes have selected people with DNA that favors resistance to
infections by causing more inflammation in the body. In doing so, this has also
contributed to making modern Africans prone to developing cardiovascular
diseases, such as atherosclerosis, later in life.
Dominguez-Andres and Netea also write about
how the early-human ancestors of Eurasians lived in regions still inhabited by
Neanderthals and interbred. Today, people with remainders of Neanderthal DNA
can be more resistant against HIV-1 and 'staph' infections, but are also more
likely to develop allergies, asthma, and hay fever.
The negative side effects of changes in each
population's immune systems are a relatively recent finding. "We know a
few things about what is happening at the genetic level in our ancestry, but we
need more powerful technology. So, next generation sequencing is bursting now
and allowing us to study the interplay between DNA and host responses at much
deeper levels," says Dominguez-Andres. "So, we are obtaining a much
more comprehensive point of view."
These technologies are also revealing how our
immune systems are evolving in real time because of modern lifestyle changes.
African tribes that still engage in hunting have greater bacterial gut
diversity than urbanized African-Americans that eat store-bought foods. Also,
changes in hygiene patterns seen in the last two centuries have improved
sanitation, drinking water, and garbage collection, and have led to reduced
exposure to infectious pathogens relative to previous times. As humans move
toward processed foods and stricter hygiene standards, their bodies adapt by
developing what researchers call "diseases of civilization," such as
type 2 diabetes.
Moving forward, Dominguez-Andres and Netea
will expand their research to communities that fall outside African and
Eurasian populations. "So far, all of the studies we went through are
focused on populations with European and African descent, but they must also be
extended to indigenous and other populations to improve the representation of
human genetic diversity," says Dominguez-Andres. "Lifestyles and
ecologic natures can really differ and influence immune responses. So, more
work needs to be done."
This work was supported by a Spinoza Grant of
the Netherlands Organization for Scientific Research and an ERC Advanced grant.
.png)
.jpg)
.gif)
