Inbred Neanderthals left humans a genetic burden

June 6, 2016, Genetics Society of America
A Neanderthal skeleton, left, compared with a modern human skeleton. Credit: American Museum of Natural History

The Neanderthal genome included harmful mutations that made the hominids around 40% less reproductively fit than modern humans, according to estimates published in the latest issue of the journal Genetics. Non-African humans inherited some of this genetic burden when they interbred with Neanderthals, though much of it has been lost over time. The results suggest that these harmful gene variants continue to reduce the fitness of some populations today. The study also has implications for management of endangered species.

"Neanderthals are fascinating to geneticists because they provide an opportunity to study what happens when two groups of humans evolve independently for a long time—and then come back together," says study leader Kelley Harris, of Stanford University. "Our results suggest that inheriting Neanderthal DNA came at a cost."

Previous studies of DNA extracted from Neanderthal remains revealed that these Eurasian were much more inbred and less genetically diverse than . For thousands of years, the Neanderthal population size remained small, and mating among close relatives seems to have been common.

Then, 50,000-100,000 years ago, groups of anatomically modern humans left Africa and moved to the homelands of their distant Neanderthal cousins. The two groups interbred, mingling their previously distinct genomes. But though a small fraction of the genome of non-African populations today is Neanderthal, their genetic contribution is uneven. Neanderthal sequences are concentrated in certain parts of the human genome, but missing from other regions.

"Whenever geneticists find a non-random arrangement like that, we look for the evolutionary forces that caused it," says Harris.

Harris and her colleague Rasmus Nielsen (University of California, Berkeley / University of Copenhagen) hypothesized that the force in question was natural selection. In small populations, like the Neanderthals', natural selection is less effective and chance has an outsized influence. This allows weakly harmful mutations to persist, rather than being weeded out over the generations. But once such mutations are introduced back into a larger population, such as modern humans, they would be exposed to the surveillance of natural selection and eventually lost.

To quantify this effect, Harris and Nielsen used computer programs to simulate mutation accumulation during Neanderthal evolution and to estimate how humans were affected by the influx of neanderthal genetic variants. The simulations incorporated data on the mutation rates, genome properties, and population dynamics of hominids.

The results suggest that Neanderthals carried many mutations with mild, but harmful effects. The combined effect of these weak mutations would have made Neanderthals at least 40% less fit than humans in evolutionary terms—that is, they were 40% less likely to reproduce and pass on their genes to the next generation.

Related conclusions were reached in an independent study that used very different methods, led by Ivan Juric at the University of California, Davis. This work is currently being peer reviewed and is available at the pre-publication preprint server bioRxiv.

Harris and Nielsen's simulations also suggest that humans and Neanderthals mixed much more freely than originally thought. Today, Neanderthal sequences make up approximately 2% of the genome in people from non-African populations. But Harris and Nielsen estimate that at the time of interbreeding, closer to 10% of the human migrants' genome would have been Neanderthal. Because there were around ten times more humans than Neanderthals, this number is consistent with the two groups acting as as single population that interbred at random. Recent DNA evidence has confirmed that the Neanderthal contribution to Eurasian genomes was higher in the past.

Although most of the harmful mutations bequeathed by our Neanderthal ancestors would have been lost within a few generations, a small fraction likely persists in people today. Harris and Nielsen estimate that non-Africans may have historically had approximately 1% lower reproductive fitness due to their Neanderthal heritage. This is in spite of the small number of Neanderthal gene variants thought to be beneficial today, including genes related to immunity and skin color.

The results also have implications for conserving endangered species. Many vulnerable populations in fragmented habitats face similar genetic problems to the Neanderthals: inbreeding, low genetic diversity, and accumulation of harmful mutations. One management strategy for overcoming these problems is genetic rescue—improving the health of an inbred population by outcrossing it with other populations.

"Genetic rescue is designed to move gene variants from an outbred population to an inbred population," says Harris. "Our results suggest managers must ensure that this movement only goes one way; otherwise harmful mutations from the inbred population may lower the fitness of the outbred group."

Explore further: A world map of Neanderthal and Denisovan ancestry in modern humans

More information: K. Harris et al, The Genetic Cost of Neanderthal Introgression, Genetics (2016). DOI: 10.1534/genetics.116.186890

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11 comments

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BSD
1 / 5 (4) Jun 06, 2016
So they didn't breed with those from the sub-continent and east Asia then? Look at their populations.
TheGhostofOtto1923
1.9 / 5 (9) Jun 06, 2016
Mingling... interbred... They make it sound so congenial. In truth what most likely happened was that whenever they came into conflict over resources, the cromags hunted their swarthy cousins for the meat and took the young females for incorporation. Because thats what theyve always done.

Neanderthal didnt have the experience over 100s of gens of heightened intertribal competition that the cromags did. Cromags were better fighters with superior weapons and tactics.

And most critically, neanderthal reproduction had most likely begun to align itself with the seasons, as with most temperate species. They could not replace battle losses as fast as the tropicals, and were consistently outnumbered and overrun.
cantdrive85
Jun 06, 2016
This comment has been removed by a moderator.
Paradox
4.4 / 5 (7) Jun 06, 2016
Re: TheGhostofOtto1923

I guess you think that because you say it - it must be so. Pshaw. You are confusing kids who might not know better. Yay you.

Neanderthal man lived for 200,000+ years , Cro-Magnon man from 45,000-to the present.
In case you didn't realize it, WE ARE Cro-Magnon men.
torbjorn_b_g_larsson
4.7 / 5 (10) Jun 06, 2016
"this number is consistent with the two groups acting as as single population that interbred at random."

And so died the the idea that Neanderthals were outcompeted, raped and killed by Anatomically Modern Humans!

I think John Hawks, that long has been arguing based on earlier data against any single factor hypothesis, be it outbreeding, exterminations. rapes, cultural differences, will be overjoyed.

@BSD: ? Asians have Neanderthal and Denisovan genes, and genes from a ghost lineage that must have been Erectus.

@TGO: Did you read the article? It was random mixing, i.e. no overweight of AMH males and N females.

Your idea is not pining, it's passed on. This idea is no more! It has ceased to be. It's expired and gone to meet its maker.This is a late idea. It's a stiff. Bereft of life, it rests in peace. If you hadn't nailed it to the comment board it would be pushing up the daisies. It's rung down the curtain and joined the choir invisible. This is an ex-idea.
huckmucus
1 / 5 (5) Jun 07, 2016
I admit I am no scientist and I don't really understand the concept of entropy. But, as a lay person, I sense what I think is it. Are my senses wrong? Probably. Who cares. In any event, everything seems to be getting smaller, dumber and more worthless; from the dinosaurs to us. And yet we think we are "all that." Our thinking that proves my point.

Does anyone see what I did there? I don't.
TheGhostofOtto1923
1.8 / 5 (5) Jun 08, 2016
Re: TheGhostofOtto1923

I guess you think that because you say it - it must be so. Pshaw. You are confusing kids who might not know better. Yay you.

Neanderthal man lived for 200,000+ years , Cro-Magnon man from 45,000-to the present.
In case you didn't realize it, WE ARE Cro-Magnon men.
Thaaats right. Read my post again or stay stupid.
TheGhostofOtto1923
2.6 / 5 (5) Jun 08, 2016
It was random mixing, i.e. no overweight of AMH males and N females
I dont see anything re males or females in the article. Youre implying that humans were loving and peaceful up until the start of recorded history? CHIMPS engage in intertribal warfare with the same results.

And its not my idea.

"According to Bowler (1986), Dart assumed from the start that Australopithecus engaged in the hunting of at least small animals, although it was only later in his career that he came to see hunting as a major force in the shaping of human nature. In his Adventures with the Missing Link of 1959, Dart now spoke openly, in a convoluted prose with high protein content, of modern humanity's loathsome cruelty as a continuation of the blood lust of our carnivorous and cannibalistic ancestors (1959, p. 201). Ardrey drove home this theme, becoming a leading exponent of what was sometimes known as the anthropology of aggression.
http://rint.recht...rid2.htm
humy
not rated yet Jun 12, 2016
What this link suggests doesn't make any evolutionary sense and appears to completely misunderstand how evolution works. If some genes from such inbreeding made some of us reproduce less efficiently or 'less fit' in some other way, unless we are talking about DNA parasites here i.e. genes that replicate at out expense, unless those same genes also give us some significant advantage that more than compensates for that 'less fit' such that it increases the overall probability of reproductive success, obviously, over many generations, natural selection would inevitably completely select out (or 'weed out' if you prefer) all of those those genes leaving as with NO such so called "genetic burden".
gkam
1 / 5 (2) Jun 12, 2016
Did we get religion from the Neanderthal, too?

It fits, doesn't it?
automaticsteam
not rated yet Jun 24, 2016
Sheesh... that's just like modern humans. Blame their damn stupidity on the Neanderthal.

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