Les relations sexuelles entre différentes espèces humaines influencent la santé moderne – Inversjanuari 15, 2020
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When Homo sapiens left Africa and encountered the Homo neanderthalensis in Europe, the two ancient hominins did the obvious thing and had sex with one another, exchanging life-saving genetic adaptions. That genetic exchange allowed human-hybrid children to skip the thousands of years of natural selection Neanderthals experienced in Europe, and inherit virus-fighting and life-saving genes fast.
Now, scientists say this influence may be more expansive than they previously thought. In fact, ancient humans’ genetic exchange could be one of the major causes of adaptive evolution in humans, according to a new study.
Using new computational methods, scientists determine that the gene flow between archaic humans affects modern-day human metabolism, our response to different types of pathogens, and a scattering of neuronal traits. The findings were published on Tuesday in Molecular Biology and Evolution.
Study authors Alexandre Gouy and Laurent Excoffier first analyzed “archaic introgression maps” for 35 Melanesian individuals. Introgression maps, Gouy tells Inverse, tell you which blocks in your genome are likely to be of archaic ancestry. They’re traced by comparing the genomes of ancient hominins — obtained from Neanderthal and Denisovan fossils — and modern humans using statistical tools.
Basically, you can “see a genome as a mosaic of blocks inherited from your ancestors,” he says. As ancient hominins interbred with modern humans, some of these blocks along the genome can be traced back to Neanderthal and Denisovan ancestors.
The researchers then looked at introgression maps across participants in the 1,000 Genomes Project. For the purposes of the study, the researchers focused on those of people from East Asia, Europe, and Papua New Guinea.
What did humans inherit?
Their analysis of patterns of introgression, along with data sets of connected genes and subnetworks, yielded complex and fascinating findings.
It’s previously been shown that the Denisovan gene EPAS1 likely helps Tibetans live in high-altitude places, and that some Neanderthal variants are associated with behavioral traits, including mood disorders and an inclination towards cigarettes.
The new study found that, in European populations, Neanderthal genes are also linked to metabolism, iron- and oxygen-binding in red blood cells and muscles, as well as olfactory receptors. Among East Asians and Europeans, ancient introgression is associated with a GABA transporter and a neurotransmitter transporter, the study suggests. In Papuans, genes showing “a significant excess of introgression” associated to autism susceptibility and attention deficit-hyperactivity disorder (ADHD) were found.
Especially intriguing was the finding the presence of introgressed mutations in Papua New Guineans that are potentially linked to resilience to malaria, Guoy says. These mutations are linked to Denisovan ancestry.
Not all inheritance is the same
Importantly, just because one has Densivoan or Neanderthal DNA in their genome that doesn’t mean that inheritance is going to show up in their genes in the same way. Each human population has a specific history, and ancient hominins interbred with modern humans at different times and in different places.
“That is why introgressed genes are sometimes specific to a population,” Gouy says. “Different people can carry the same amount of Neanderthal DNA, but it can be found in different places of their genome.”
For example: The region of the genome that may be involved in resistance to malaria among Papua New Guineans is inherited from Denisovans. These mutations are almost always found in Melanesians and Aboriginal Australians — which is why they aren’t present across the global population.
It’s also not as simple as saying because a person with Neanderthal DNA has ADHD, then Neanderthals had ADHD. While this study points out that Denisovan and Neanderthal-inherited genes are related to health and behavior, “it remains very difficult to quantify precisely the effect of those mutations,” Guoy says.
“What we can say so far is that some introgressed mutations have been associated to neurological processes,” he says. “We cannot know yet precisely how it will affect the health or behavior of an individual, based on genomic data only.”
A different way of examining gene interactions
The study is based on two novel approaches, Guoy says. One allows researchers to find networks of genes showing an excess of introgression in particular populations, and the one to other tests whether specific mutations in certain genes tend to be found together in modern individuals. That clumping is known as when genes are “co-introgressed.”
These techniques allowed them to gain new insights by examining the data from a network-interaction perspective. Gouy says that they can see their approach as complementing more traditional methods that focus on single genes, this simply allows them to take a different perspective on the same data.
“I personally find it fascinating to see that interbreeding with other human lineages shaped human adaptations,” Gouy says. “As we were developing approaches to understanding modern human adaptations by looking at gene interactions, we realized that such interactions for Neanderthal and Denisova-inherited mutations had been overlooked.”
The results from genomic studies need to be interpreted with caution, Gouy says. Behavior results from a complex interaction of genes and the environment — and it’s difficult to assess the full impact genes have.
But it is obvious that the interaction between genes affects us in some way, and historically our archaic mutations have been overlooked. These played a role in human evolution and health, and more research is needed to know the full extent.
Anatomically modern humans carry many introgressed variants from other hominins in their genomes. Some of them affect their phenotype and can thus be negatively or positively selected. Several individual genes have been proposed to be the subject of adaptive introgression, but the possibility of polygenic adaptive introgression has not been extensively investigated yet. In this study, we analyze archaic introgression maps with refined functional enrichment methods to find signals of polygenic adaptation of introgressed variants. We first apply a method to detect sets of connected genes (subnetworks) within biological pathways that present higher-than-expected levels of archaic introgression. We then introduce and apply a new statistical test to distinguish between epistatic and independent selection in gene sets of present-day humans. We identify several known targets of adaptive introgression, and we show that they belong to larger networks of introgressed genes. After correction for genetic linkage, we find that signals of polygenic adaptation are mostly explained by independent and potentially sequential selection episodes. However, we also find some gene sets where introgressed variants present significant signals of epistatic selection. Our results confirm that archaic introgression has facilitated local adaption, especially in immunity related and metabolic functions and highlight its involvement in a coordinated response to pathogens out of Africa.