Diseases related to IBD, including Crohn’s Disease and Ulcerative Colitis, are increasingly prevalent in modern society. Similarly, Psoriasis, a common chronic inflammatory skin condition that involves red elevated patches and flaking silvery scales as well as causing rashes that itch and sting, continues to be widespread health issue in the world today.
Scientists at the State University of New York at Buffalo are intrigued as to why a genetic susceptibility to Crohn’s Disease, Psoriasis and other diseases persist for hundreds of thousands of years, afflicting both our ancient ancestors, and us, having discovered that genetic variations associated with certain modern medical disorders reach back to distant antiquity, predating the Neanderthals and Denisovans (another ancient hominid), as well as contemporary humans.
The study led by SUNY Buffalo biologist Omer Gokcumen compared modern human DNA to that of Neanderthals and Denisovans, and 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.
The findings of the SUNY Buffalo study were published last month in the journal Molecular Biology and Evolution in a paper entitled “The Evolution and Functional Impact of Human Deletion Variants Shared with Archaic Hominin Genomes“ (Mol Biol Evol (2015) doi: 10.1093/molbev/msu405 First published online: January 2, 2015), coauthored by Yen-Lung Lin and Omer Gokcumen (corresponding author) of the Department of Biological Sciences at SUNY Buffalo; Pavlos Pavlidis of the Institute of Molecular Biology and Biotechnology (IMBB) at the Foundation of Research and TechnologyHellas, in Heraklion, Crete, Greece; Emre Karakoc of the Department of Evolutionary Genetics at the Max Planck Institute for Evolutionary Biology in Pln, Germany; and Jerry Ajay of the SUNY Buffalo Department of Computer Science and Engineering.
The coauthors say the release of ancient Neandertal and Denisovan genomes allowed them to study the relationship between genomes of ancient hominids and modern humans, noting that Neandertal and Denisovan genomes are more closely related to each other than they are to modern human genomes and they diverged from modern human ancestors approximately 500,000 years ago. However, they observe that recent studies show archaic hominins, including but not limited to Neanderthals and Denisovans, contributing genetic material to modern humans, and that the origin and impact of these introgressions vary geographically and involve different specie.
The researchers note that while Allele sharing between modern and archaic hominin genomes has been variously interpreted to have originated from ancestral genetic structure or through non-African introgression from archaic hominins, evolution of polymorphic human deletions shared with archaic hominin genomes has yet to be studied.
The research team had previously described a common deletion polymorphism in modern humans that is shared with Neandertal and Denisovan genomes (Gokcumen et al. 2013), and reasoned that this deletion must have evolved before HumanNeandertal/Denisovan divergence in Africa and been maintained through balancing selection. In this paper they extend their analyses to the entire genome in order to identify deletion variants observed among modern humans that are shared with Neandertal and Denisovan genomes.
Ergo, some of our early ancestors had telltale features, called deletions, while others did not, which mirrors variation in modern humans, and the scientists deduce that this genetic diversity may date as far back as a million or more years ago in a primitive common ancestor of humans, Denisovans and Neanderthals.
“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 SUNY Buffalo assistant professor of biological sciences.
The scientists say their discovery highlights the importance of balancing selection — the poorly understood evolutionary dance in which conflicting forces impel species to retain diverse genetic feature sets this new research posits the possibility that the diseases in question — or at least a genetic susceptibility to them — “may have been with us for a long time,” says Dr. Gokcumen.
Why evolution would play out this way remains an open question, but the scientists suggest that one possibility might be that certain traits making humans susceptible to Crohn’s and psoriasis may also have provided 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,” Dr. 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 sickle cell anemia remains in the population in malaria-ridden geographies.”
The new Molecular Biology and Evolution study suggests that ancient deletions associated with Crohn’s disease and psoriasis may play similar but likely more complex roles in human 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 genetic features that may increase susceptibility for these conditions,” Dr. Gokcumen observes. “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 opposingevolutionary pressures may be under appreciated,” says paper coauthor in the study Yen-Lung Lin, a PhD candidate in SUNY Buffalo’s Department of Biological Sciences and member of the Gokcumen lab for evolutionary and anthropological genomics research group. “We’re thinking forces that maintain variation might be more relevant to human health and biology than previously believed.”
Important Genetic Variations Predate Neanderthals
A SUNY Buffalo release notes that Dr. Gokcumen’s team compared modern human genomes to genomes of other closely related species, including chimpanzees as well as Neanderthals and Denisovans, both of which evolved hundreds of thousands of years ago and whose genomes have been sequenced by other scientists using ancient remains. The scientists identified DNA chunks that exist in chimpanzees but were later erased through evolutionary processes — the fore-noted deletions, which today are present in some human genomes and missing from others.
The scientists found that certain functionally important deletions, the presence of which varies among modern humans, likely originated in one of our common ancestors, the Neanderthals or the Denisovans, possibly dating as far back as a million or more years in the past. These extraordinarily old deletions included ones common in Crohn’s disease today, and in psoriasis patients, as well as deletions linked to an individual’s ability to respond to certain drug therapeutics, including growth hormone treatments.
The SUNY Buffalo release notes that In previous research, scientists conducted similar studies examining genetic variations that consist of single units of DNA called nucleotides. This new research investigated longer DNA sequences, taking advantage of recently available genomic data of both modern and ancient hominins, demonstrating the power of leveraging this sort of data in investigating various genetic differences among humans and to illuminate our species’s genetic history.
State University of New York at Buffalo
Molecular Biology and Evolution
State University of New York at Buffalo