 |
| A reconstruced Neanderthal with a modern human girl. |
Neanderthal Left Humans Genetic Burden, Scientists Say. Sci-News.com, June 6, 2016.
Neanderthal Mutations Could Still be Affecting Humans. By Daryl Worthington. New Historian, June 7, 2016.
Here’s why human women probably struggled to have babies with Neanderthal men. By Rafi Letzter. Tech Insider, June 6, 2016.
The Divergence of Neandertal and Modern Human Y Chromosomes. By Fernando L. Mendez et al. American Journal of Human Genetics, Vol. 98, No. 4 (April 7, 2016). PDF.
The Genetic Cost of Neanderthal Introgression. By By Kelley Harris and Rasmus Nielsen. Genetics, Vol. 203, No. 2 (June 2016). PDF.
Abstract:
Approximately
2–4% of genetic material in human populations outside Africa is derived from
Neanderthals who interbred with anatomically modern humans. Recent studies have
shown that this Neanderthal DNA is depleted around functional genomic regions;
this has been suggested to be a consequence of harmful epistatic interactions
between human and Neanderthal alleles. However, using published estimates of
Neanderthal inbreeding and the distribution of mutational fitness effects, we
infer that Neanderthals had at least 40% lower fitness than humans on average;
this increased load predicts the reduction in Neanderthal introgression around
genes without the need to invoke epistasis. We also predict a residual
Neanderthal mutational load in non-Africans, leading to a fitness reduction of
at least 0.5%. This effect of Neanderthal admixture has been left out of
previous debate on mutation load differences between Africans and non-Africans.
We also show that if many deleterious mutations are recessive, the Neanderthal
admixture fraction could increase over time due to the protective effect of
Neanderthal haplotypes against deleterious alleles that arose recently in the
human population. This might partially explain why so many organisms retain
gene flow from other species and appear to derive adaptive benefits from
introgression.
Sci-News.com:
The genome of Neanderthals contained
harmful gene variants that made them around 40 percent less reproductively fit
than modern humans. And non-Africans inherited some of this genetic burden when
they interbred with our extinct cousins, say genetic researchers.
Several
previous studies revealed that Neanderthals
were much more inbred and less genetically diverse than modern humans. For
thousands of years, the Neanderthal population size remained small, and mating
among close relatives seems to have been common.
Then,
between 100,000 and 50,000 years ago, anatomically modern Homo sapiens left Africa and moved to the homelands of their
distant 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,” said Dr. Kelley Harris of Stanford
University.
Dr.
Harris and her co-author, Dr. Rasmus Nielsen from the University of California,
Berkeley, and the 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, the scientists used computer programs to simulate
mutation accumulation during Neanderthal evolution and to estimate how humans
were affected by the influx of Neanderthal genetic variants.
“To
assess the fitness effects of Neanderthal introgression on a genome-wide scale,
we used forward-time simulations incorporating linkage, exome architecture, and
population size changes to model the flux of deleterious mutations across
hominin species boundaries,” the scientists said.
The
results, published in the journal Genetics, suggest that
Neanderthals carried many mutations with mild, but harmful effects.
The
combined effect of these mutations would have made Neanderthals at least 40
percent less fit than Homo sapiens in evolutionary terms.
The
team’s simulations also suggest that humans and Neanderthals mixed much more
freely than originally thought
Today, Neanderthal sequences make up approximately 2 percent of the genome in people from
non-African populations. But the scientists estimate that at the time of interbreeding,
closer to 10 percent of the human migrants’ genome would have been Neanderthal.
Because
there were around 10 times more humans than Neanderthals, this number is
consistent with the two groups acting as a single population that interbred at
random.
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.
The
team estimates that non-Africans may have historically had approximately 1
percent 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.
Worthington:
Breeding
with Neanderthals may have had a heavy price for early humans, according to a
new study published recently in the journal GENETICS.
Harmful
mutations present in the genome of Neanderthals made them up to 40% less fit
reproductively than modern humans, according to the study. Although most of the
effects have since been lost to time, these mutations likely passed to
non-African humans when they interbred with Neanderthals. It is suggested that
the mutations could still be affecting the fitness of some populations today.
The
study was led by Kelley Harris of Stanford University, along with her colleague
Rasmus Nielse, from the University of California Berkley and Copenhagen
University.
“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,” Harris explained. “Our results suggest that
inheriting Neanderthal DNA came at a cost.”
It is
now widely accepted that modern humans interbred with Neanderthals, our closest
extinct genetic relatives, with between 2% and 4% of genetic material in
modern, non-African human populations having a Neanderthal origin. A study
published earlier this year suggested that anything from the risk of depression
to nicotine addiction could be connected to the mixing of human and Neanderthal
genomes.
Due to
their smaller, more concentrated population, inbreeding was much more common
among Neanderthals than modern humans, leading to their decreased genetic
diversity.
Harris
and Nielsen were particularly fascinated by the fact that the Neanderthal
genetic contribution to the modern human genome is uneven, but not random.
Neanderthal sequences tend to be concentrated in certain areas, but totally
absent elsewhere.
“Whenever
geneticists find a non-random arrangement like that, we look for the
evolutionary forces that caused it,” Harris remarked.
They
hypothesised that the explanation could be found in natural selection. In small
populations, like the Neanderthals, natural selection is less effective, allowing
mutations to persist and have a larger influence. If such a mutation is
introduced back into a larger population (such as modern humans) however, it’s
quickly lost in the march of natural selection.
To
understand this process, Harris and Nielsen used computer programs to simulate
mutation accumulation during Neanderthal evolution and estimate how humans were
affected by the influx of Neanderthal genetic variants. They concluded that
Neanderthals would have carried many mild, harmful mutations, combining to make
them 40% less fit than humans in evolutionary terms.
Their
results also suggest that humans and Neanderthals had actually interbred much
more freely and frequently than previously believed. The findings suggest that
thousands of years ago, when both humans and Neanderthals inhabited the earth,
closer to 10% of non-African humans’ genomes would have been Neanderthal.
Shockingly,
Harris and Nielsen suggest that a fraction of the harmful Neanderthal genetic
mutations could still be present in modern human populations. They estimate the
result could be a 1% lower reproductive fitness in modern day non-Africans.
Letzter:
Imagine
a couple living between 39,000 and 45,000 years ago. She’s a human. He’s a Neanderthal. Their
families aren’t thrilled with the union, but they’ve learned to deal with it.
Their
union isn’t all that unusual after all – enough humans and Neanderthals made
babies together in the 5,000-plus years that the two species coexisted that
modern humans now owe about 4% of our DNA to our extinct nonhuman kin.
As this
human-Neanderthal couple moves through life, like many couples, they have
children. A daughter, and then another daughter, and then another. And they
notice something funny: All their Neanderthal man/human woman couple friends
keep having daughters as well.
That
mystery may have puzzled them, and its genetic legacy has puzzled modern
scientists as well. While traces of all sorts of Neanderthal DNA show up in the
human genome, scientists haven’t found any Neanderthal Y-chromosomes – the
chromosomes fathers pass to biologically male children. That doesn’t necessarily mean the Neanderthal
Y-chromosome is extinct, but it makes it likely.
There
are a number of theories as to why the Neanderthal Y has vanished, the most
popular until recently being the vagaries of random chance. That is, that male
children were born to Neanderthal-human couples, but their genes were rare
enough not to survive through the ages.
But a study published recently in the American Journal of Human Genetics suggests an alternate explanation: Human
women may have been unable, or at least struggled, to carry male
half-Neanderthal fetuses to term. That’s because of three genes found on the
Neanderthal Y-chromosome that are known to trigger immune responses in human
beings. Those genes could have caused human mothers’ immune systems to attack
male half-Neanderthal fetuses, triggering miscarriages.
Even if
half-Neanderthal baby boys with human mothers were born occasionally, that
genetic incompatibility could have weeded out enough of them to eventually
remove their traces from the gene pool.
The
paper’s authors caution that their results are not conclusive – they’ve
identified a possible cause, not shown it to be the case. But for bemused
parents at ancient play groups full of little half-Neanderthal girls (as well
as modern scientists) this result might have sated some curiosity.
