# Population Genetics > Paleogenetics > Paleolithic & Mesolithic >  How Neanderthals made us sick

## Angela

And gave us some immunity.

See:
David Enard et al
https://www.cell.com/cell/fulltext/S...ecsectitle0010



"Neanderthals and modern humans interbred at least twice in the past 100,000 years. While there is evidence that most introgressed DNA segments from Neanderthals to modern humans were removed by purifying selection, less is known about the adaptive nature of introgressed sequences that were retained. We hypothesized that interbreeding between Neanderthals and modern humans led to (1) the exposure of each species to novel viruses and (2) the exchange of adaptive alleles that provided resistance against these viruses. Here, we find that long, frequent—and more likely adaptive—segments of Neanderthal ancestry in modern humans are enriched for proteins that interact with viruses (VIPs). We found that VIPs that interact specifically with RNA viruses were more likely to belong to introgressed segments in modern Europeans. Our results show that retained segments of Neanderthal ancestry can be used to detect ancient epidemics."

See also:
https://www.nytimes.com/2018/10/04/science/neanderthal-genes-viruses.html

Some of the viruses to which they exposed us include influenza, herpes, and HIV.

Well, I guess good for us, but it must have sucked for our homo sapiens, sapiens ancestors. 

It also strikes me we're not actually immune to any of those three listed diseases.

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## halfalp

I love the concept of " purifying selection " sounds like something we dream about, but absolutely doesn't exist. Also saying that Neanderthals exposed use to Influenza, Herpes, HIV doesn't make sense. Non africans that dont have neanderthals variants, are still vulnerable to AIDS. Also, Influenza, coming from bacterium is more trigger in cold climates, when the immune defense are more fragile, wich doesn't really make correlation with how AIDS evolve. Sounds like they make a lot of random correlations without actually genomic proofs to how neanderthals would reacte to those. Typically the HIV one, i feel the take this route " so HIV is an African decease, so because Neanderthals must have been so far unrelated to modern africans, the should have a way faster progression of AIDS if they would be affected ".

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## Angela

> I love the concept of " purifying selection " sounds like something we dream about, but absolutely doesn't exist. Also saying that Neanderthals exposed use to Influenza, Herpes, HIV doesn't make sense. Non africans that dont have neanderthals variants, are still vulnerable to AIDS. Also, Influenza, coming from bacterium is more trigger in cold climates, when the immune defense are more fragile, wich doesn't really make correlation with how AIDS evolve. Sounds like they make a lot of random correlations without actually genomic proofs to how neanderthals would reacte to those. Typically the HIV one, i feel the take this route " so HIV is an African decease, so because Neanderthals must have been so far unrelated to modern africans, the should have a way faster progression of AIDS if they would be affected ".



What ????????????????

The only correlation between influenza and cold weather is the fact that when it's cold human beings cluster together indoors more, and so transmission is more facilitated. It also lives in heating vents etc. COLD doesn't GIVE it to you.

Purifying selection can be seen in the genes; it's not MADE UP. This is part of evolution. Mutations happen. Most are neutral, a few are beneficial, some are really bad and so get weeded out pretty fast because people die before they can procreate (i.e. the mating problems of hybrid sapiens/Neanderthal blends), and some are just small effect negative but in combination can be a problem. Evolution consists in the environment selecting for and against certain genes. 

HIV is NOT an African disease. There are a lot of reasons why it is more prevalent in Africa, including different sexual mores, different sexual practices, and lack of use of condoms. (There are northern Europeans who die of AIDS too, if they are exposed to the virus.)

However, it is also true that Africans may, PERHAPS, have less resistance to it, leading to faster progression, and that MAY perhaps be due, in part, to inheriting less immunity to it, an immunity which MIGHT be partly conferred by Neanderthal or MORE inheritance. The VIRUS has apparently been present in the world since the time of the Neanderthals. You don't INHERIT the VIRUS. You INHERIT more or less immunity to it.

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## halfalp

> What ????????????????
> 
> *The only correlation between influenza and cold weather is the fact that when it's cold human beings cluster together indoors more, and so transmission is more facilitated. It also lives in heating vents etc. COLD doesn't GIVE it to you.*
> 
> Purifying selection can be seen in the genes; it's not MADE UP. This is part of evolution. Mutations happen. Most are neutral, a few are beneficial, some are really bad and so get weeded out pretty fast because people die before they can procreate (i.e. the mating problems of hybrid sapiens/Neanderthal blends), and some are just small effect negative but in combination can be a problem. Evolution consists in the environment selecting for and against certain genes. 
> 
> HIV is NOT an African disease. There are a lot of reasons why it is more prevalent in Africa, including different sexual mores, different sexual practices, and lack of use of condoms. (There are northern Europeans who die of AIDS too, if they are exposed to the virus.)
> 
> However, it is also true that Africans may, PERHAPS, have less resistance to it, leading to faster progression, and that MAY perhaps be due, in part, to inheriting less immunity to it, an immunity which MIGHT be partly conferred by Neanderthal or MORE inheritance. The VIRUS has apparently been present in the world since the time of the Neanderthals. You don't INHERIT the VIRUS. You INHERIT more or less immunity to it.


Haha, yes i know cold doesn't give you Influenza, i meant, cold times make your immune systeme less performant and more open to sickness. This is why Influenza is a winter sickness mostly. ( I never had it ).

AIDS is a virus think to come from some African Monkeys and evolved in humans because they eated some infected specimens at some point. Every humans can be affected by AIDS, but it is absolutely not native from outside of Africa and is a pretty recent decease. And i think in countrary that Africans are more chance to be not immune, but with a slower progression to AIDS than most of humans. One of the first north american to have HIV " sort of patient 0 ", was if i remember a Marine Canadian openly Gay who made escale in Africa at some point. It propagated a lot with junkies, homosexual and non-protected relations.

But for the main point, i dont understand the relationship they make with Neanderthals and HIV wich have less than 200 years of existence. Do they made some weird experiences with some neanderthals dna and HIV in Bio Lab and see how it evolved?

I'm always cautious with the all, relationship between your DNA, Haplogroup, Ancestry and the progression of certain type of deceases. Like apparently individuals with mtdna U5a would be ultra sensitive to HIV.


Edit: You gotta the like the guy who always put negative rating without saying anything...

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## Gnarl

Yes, HIV is a very recent disease. Molecular clock indicates that it made the jump from SIV, the simian version around 1900. I've read some good speculation connecting it to the holocoust of King Leopold of Belgium in Congo.

But I'm going to ask for some very good cites on cold reducing your immune system performance. Body temperature is within a narrow range of temperatures regardless of outside temperature, and if anything it seems the increased metabolism you need to keep your temperature in colder climates should keep things on the hop.

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## Angela

The body of the paper clarifies the issue.

"Because viruses appear to have driven so much adaptation in the human lineage, and because it is plausible that when Neanderthals and modern humans interbred they also exchanged viruses either directly by contact or via their shared environment, we hypothesized that some introgressed sequences might have provided a measure of protection against the exchanged viruses and were driven into the recipient species by positive directional selection. "

"Consistent with this model, several cases of likely adaptive introgression (Gittelman et al., 2016
, Racimo et al., 2015
, Racimo et al., 2017
) from Neanderthals to modern humans involve immune genes that are specialized to deal with pathogens including viruses (Abi-Rached et al., 2011
, Dannemann et al., 2016
, Deschamps et al., 2016
, Houldcroft and Underdown, 2016
, Mendez et al., 2012
, Mendez et al., 2013
, Nedelec et al., 2016
, Quach et al., 2016
, Sams et al., 2016
)."

"we found that VIPs that specifically interact with RNA viruses are particularly enriched in Neanderthal IS in modern European genomes compared to VIPs that interact with DNA viruses. We provide a number of arguments suggesting that it is specifically adaptation in response to viruses that drove these enrichments. We next identify several viruses as likely agents of selection, as well as a number of specific VIPs as likely targets of adaptation. Finally, we estimate that adaptation overall, and specifically adaptation in response to viruses, was an important force in the history of those Neanderthal IS that were ultimately retained in modern human genomes."

*"related* viruses tend to use similar *host VIPs* (Enard et al., 2016
). For example, *VIPs interacting with HIV are also likely to interact with other lentiviruses.* Thus,* if enrichment of adaptive introgressions of HIV-interacting VIPs is observed, this presents evidence of past adaptation related to a lentivirus rather than to HIV itself*."

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## halfalp

I think what's the most confusing with the paper is that it takes different deceases with totally different pattern into the same bowl. For exemple, Influenza is a sickness that evolved every year, so you can basically every year have Influenza and not have immunity or very low, now people from cold places are the more exposed to Influenza and then having more chance to have little immunity for it. So how Africans without Neanderthal genes would be immune to Influenza? They are obviously not, they are saying " those reasons coming neanderthals [ made us sick ] " but you would be sick " without those reasons " still.

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## bigblob

Neanderthal and modern humans interbred a lot more times than twice. Just about all ancient Paleolithic European skulls have Neanderthal affinities. 

As for HIV, its a recent disease and has nothing to do with Neanderthals. Modern Eurasians are said to have inherited their immune system from Neanderthals.

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