Did genetic links to modern maladies provide ancient benefits?

Did genetic links to modern maladies provide ancient benefits?
A reconstruction of Homo neanderthalensis, as created by artist John Gurche for the Smithsonian's National Museum of Natural History. A study led by University at Buffalo biologist Omer Gokcumen compared the DNA of modern humans to Neanderthals and Denisovans (another ancient hominin). The research found that genetic deletions associated with various aspects of human health, including psoriasis and Crohn's disease, likely originated in a common ancestor of the three species. Credit: From Shaping Humanity, by John Gurche.

Psoriasis, a chronic skin condition, can cause rashes that itch and sting.

So why would a to this and other ailments persist for hundreds of thousands of years, afflicting our ancient ancestors, and us?

That's the question scientists are asking after discovering that genetic variations associated with some modern maladies are extremely old, predating the evolution of Neanderthals, Denisovans (another ancient hominin) and contemporary humans.

The study was published this month in Molecular Biology and Evolution.

"Our research shows that some genetic features associated with psoriasis, Crohn's disease and other aspects of human health are ancient," says senior scientist Omer Gokcumen, PhD, a University at Buffalo assistant professor of .

Some of humanity's early ancestors had the telltale features, called deletions, while others did not, mirroring the variation in , the scientists found. This genetic diversity may have arisen as far back as a million or more years ago in a of humans, Denisovans and Neanderthals.

The discovery highlights the importance of balancing selection, a poorly understood evolutionary dance in which dueling forces drive species to retain a diverse set of genetic features.

The research raises the possibility that the diseases in question—or at least a genetic susceptibility to them—"may have been with us for a long time," Gokcumen says.

Why this would happen is an open question, but one possibility is that certain traits that made humans susceptible to Crohn's and psoriasis may also have afforded an evolutionary benefit to our ancient ancestors.

Dueling forces shape evolution:

Though we often think of evolution as black and white—a trait is either good or bad—there are instances where the line is not so clear, Gokcumen says.

"The best example of this is sickle cell anemia," he explains. The disorder causes red blood cells to take on a curved, crescent-like shape, which leads to anemia (a problem), but also protects against malaria by keeping parasites out of cells (an advantage). These opposing pressures create a balance where the copy of the gene that causes the remains in the population in malaria-ridden geographies.

The new study hints that the ancient deletions that are associated with Crohn's disease and psoriasis may play similar—but likely more complex—roles in health.

"Crohn's disease and psoriasis are damaging, but our findings suggest that there may be something else—some unknown factor now or in the past—that counteracts the danger when you carry that may increase susceptibility for these conditions," Gokcumen says. "Both diseases are autoimmune disorders, and one can imagine that in a pathogen-rich environment, a highly active immune system may actually be a good thing even if it increases the chances of an auto-immune response."

Ancient genetic variations maintained due to opposing evolutionary pressures may be "underappreciated," says Yen-Lung Lin, a PhD candidate in UB's Department of Biological Sciences who is lead author in the study. "We're thinking forces that maintain variation might be more relevant to and biology than previously believed."

Important genetic variations predate Neanderthals

Gokcumen's team compared modern human genomes to those of other closely related species, including chimpanzees and two archaic hominins: Neanderthals and Denisovans, both of which evolved hundreds of thousands of years ago and whose genomes were sequenced by other scientists using ancient remains.

Gokcumen's team identified chunks of DNA that exist in chimpanzees but that were later erased through evolutionary processes. These DNA segments are called deletions, and today, they are present in some human genomes and missing from others.

The study found that certain functionally important deletions that vary among modern humans likely originated in a common ancestor of humans, Neanderthals and Denisovans, possibly dating as far back as a million or more years ago. These unusually old deletions included ones that are common in Crohn's disease and psoriasis patients, as well as deletions linked to a person's ability to respond to a number of drugs, including growth hormone treatments.

In the past, scientists have conducted similar studies examining genetic variations that consist of a single unit of DNA called a nucleotide. The new research investigated longer sequences of DNA, taking advantage of recently available genomic data for modern and ancient hominins. The study demonstrates the power of leveraging such data to investigate different types of genetic differences among humans and to illuminate our species' genetic history.

Explore further

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More information: Molecular Biology and Evolution, mbe.oxfordjournals.org/content … /01/22/molbev.msu405
Journal information: Molecular Biology and Evolution

Citation: Did genetic links to modern maladies provide ancient benefits? (2015, January 28) retrieved 16 September 2019 from https://phys.org/news/2015-01-genetic-links-modern-maladies-ancient.html
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Jan 30, 2015
News article excerpt: "...sickle cell anemia," ... causes red blood cells to take on a curved, crescent-like shape, which leads to anemia (a problem), but also protects against malaria by keeping parasites out of cells (an advantage). These opposing pressures create a balance where the copy of the gene that causes the sickle cell anemia remains in the population in malaria-ridden geographies."

Journal article excerpt: "...it is plausible that complex mutational and adaptive mechanisms may have shaped the haplotypes carrying some of the deletion variants, leaving complicated signatures of adaptation."

Like Lynch et al (2015) they extracted the pseudoscientific nonsense about beneficial mutations from evolutionary theory. Many biologically uninformed researchers think a sickle cell mutation causes the disease. Instead, one of 1180 nutrient-dependent hemoglobin variants is linked to genomic stability. http://www.cell.c...)01105-X

Jan 30, 2015
So the variant came about because it makes that particular locus in the DNA more stable? What good is DNA stability if sickle cell is going to kill you anyway? What evidence is there that the sickle cell allele is more stable? What's the difference in melting point between the wild type allele and the sickle cell allele? If there is a difference, is it statistically significant?

Jan 30, 2015
Someone else just confirmed that hemoglobin S is not a mutation. You have repeatedly asserted its importance to the theory of evolution via natural selection and placed it into the same context as peppered moth natural selection via bird predation.

The nutrient-dependent pheromone-controlled physiology of reproduction linked all crustaceans to all insects via the conserved molecular mechanisms of RNA-mediated amino acid substitutions in 2015 SICB presentations that attest to the validity of my model.

Nutrient-dependent/pheromone-controlled adaptive evolution: a model. http://www.ncbi.n...24693353

Yet here you are again asking ridiculous questions that have nothing to do with what this article claims, what my model details, and what every serious scientist knows about how ecological variation leads to ecological adaptations.

You believe that mutagenesis experiments explain evolution. Science idiots should not pose questions to serious scientists.

Jan 30, 2015
Science idiots should not pose questions to serious scientists.

Then maybe you should take a seat Skippy. Yeah, over in the corner there. Yeah, you got to wear the silly looking pointy cap. And quit interrupting the serious scientists, no wonder you can't learn anything.

Jan 30, 2015
Someone else just confirmed that hemoglobin S is not a mutation.

Who? Ask them yourself. I'm sure it will end the same way Stumpy's and my conversations with Extavour, Chelo, Fink, Ian Welsh, Diamond, Ellis, etc.

RNA-mediated amino acid substitutions

Of which you've never explained the mechanism (methylation can only do so much, as I've explained previously).

Jan 30, 2015
You stage your questions to other serious scientists to elicit the answers you want to hear.

Lynch et al (2015) and these authors clearly eliminate mutations and substitute the conserved molecular mechanisms that link the nutrient-dependent biophysically-constrained chemistry of protein folding to fixation of the amino acid substitutions via the physiology of reproduction.

Nutrient-dependent reproduction links feedback loops to chromatin loops in the context of links from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man.

See also: A recurrent regulatory change underlying altered expression and Wnt response of the stickleback armor plates gene EDA http://elifescien...fe.05290 "...regulatory changes are a predominant mechanism
underlying adaptive evolution in sticklebacks (Jones et al. 2012) and other organisms
(Wray 2007, Carroll 2008)."

Jan 31, 2015
The biologically uninformed continue to yell: MUTATIONS! (JVK, DEC 18, 2014)

I'll let your own words do the talking, JVK, since you have YET AGAIN introduced that term to a thread. You just can't help yourself.


Feb 02, 2015
Science idiots should not pose questions to serious scientists.

As you are not a scientist, but rather an intentionally annoying crank, I won't follow that thread any further. I would be pleased to be considered to be a science idiot by the likes of you.

And please resist the temptation to dust off that mouldering list of your publications. About as effective as bragging about the 'A' grades earned in high school.

One thing is clear. You have personal issues. Repeatedly subjecting yourself to abuse in these fora comfortably fits that famous definition of insanity.

Feb 02, 2015

"...our theory is a synthesis of systems and metabolic approaches that shows explicitly and quantitatively how organisms control the carbon cycle at all scales from individuals to ecosystems to the biosphere."

If you cannot grasp the fact that carbon cycles are nutrient-dependent and pheromone-controlled in the context of the biophysically constrained chemistry of protein folding in species from microbes to man, you probably should not make any claims about me.

You have personal issues.
Of course I do.

They were included in Obama's "State of the Union Address" because there is a clear need to link metabolic networks and genetic networks, which is what I did in my model via the common pathways that link nutrigenomics and pharmacogenomics in the fight against the pseudoscientiific nonsense of evolutionary theory.

Feb 02, 2015

"Dr. Francis S. Collins... [author of "The Language of God"] ... said the studies would help doctors decide which treatments would work best for which patients. Such analysis can identify millions of genetic variants, providing information that would help diagnose or treat some diseases, officials said."

Combating Evolution to Fight Disease http://www.scienc...88.short

Excerpt: "nothing in evolution makes sense except in the light of biology." Although the latter might be an exaggeration, an important gap is being filled by molecular understanding of the genesis of variation that confers the ability to evolve.

Ecological variation confers the ability to adapt via the nutrient-dependent pheromone-controlled physiology of reproduction.That is what is currently understood about the creation of variation.

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