New evidence on Neanderthal mixing

October 23, 2014 by Alvin Powell
Starting with a 45,000-year-old Siberian thighbone, research by Qiaomei Fu (right), a postdoctoral fellow at Harvard Medical School, and Professor David Reich has narrowed the window of time when Neanderthals and humans crossbred. “Even if we cannot be sure of whether all the interbreeding occurred at once, the big picture is that we can be sure that the recent ancestors of this individual interbred with Neanderthals,” said Fu. Credit: Jon Chase/Harvard Staff Photographer

New research on a 45,000-year-old Siberian thighbone has narrowed the window of time when humans and Neanderthals interbred to between 50,000 and 60,000 years ago, and has shown that modern humans reached northern Eurasia substantially earlier than some scientists thought.

Qiaomei Fu, a postdoctoral fellow at Harvard Medical School (HMS) and first author of a paper describing the research, said the sample had a long history before making its way into her hands.

The bone was found eroding out of a Siberian riverbank, but no one knows precisely where. The bone changed hands several times before finding its way to the Max Planck Institute for Evolutionary Anthropology in Germany, where Fu was working with professors Janet Kelso and Svante Pääbo. Fu put the finishing touches on the research after she started in the laboratory of David Reich, HMS genetics professor.

Carbon dating and molecular analysis filled in many of the blanks about the sample. Testing determined that the sample was from an individual who lived 45,000 years ago on a diet that included plants or plant eaters and fish or other aquatic life.

Reich and Fu said the sample was remarkable because of the extraordinary preservation of its DNA, which allowed Fu, using the latest techniques for ancient DNA analysis, to extract a high-quality genome sequence. The sequence, Reich said, is significantly higher in quality than most genome sequences of present-day people generated for analysis of disease risk.

The sequence revealed that the bone came from a , a man whose remains are the oldest ever found and carbon-dated outside of Africa and the Middle East. Comparison to diverse humans around the world today showed that the man was a member of one of the most ancient non-African populations.

"The ancient Siberian was related equally to West European hunter-gatherers, North Asian hunter-gatherers, East Asians, and the indigenous people of the Andaman Islands off South Asia," Fu said. "The fact that this population separated so early indicates that theories of an early split of people who followed a coastal route to Australia, New Guinea, and coastal Asia are not strongly supported by this data."

The research, the forefront of which was in Germany and involved international collaborators including Reich, was published today in the journal Nature.

One important aspect of the research is that it obtained a high-resolution estimate of the mutation rate in humans, Fu said.

Prior research had given scientists evidence of two possible rates, one twice as fast as the other. Because of this large range, dates obtained from genetic studies have tended to be quite uncertain. By measuring the number of mutations missing in this individual and comparing with people now, Fu was able to obtain an accurate estimate of the rate that mutations accumulated over time. Her work came down definitively on the side of a slower mutation rate, corresponding to between one to two mutations per genome per year.

"This is a huge biological result. It's very important," Reich said. "I was a partisan of the fast rates until I saw these results. Qiaomei's work convinced me that the slow rates were correct."

Reich said the findings on have sweeping implications, and provide a basis for reinterpreting key dates in human prehistory. Instead of humans and Neanderthals becoming distinct offshoots sometime between 270,000 and 380,000 years ago, for example, the slower rate would put that shift much further back in time, between 550,000 and 770,000 years ago. Similarly, the slower rate pushes back estimates for the date of the separation of African and non-African populations.

"The slow mutation rates indicate that the present-day subdivisions among human populations date back to almost 200,000 years ago, well before the period around 50,000 years ago when the archaeological record documents art and new styles of toolmaking," Reich said. "The implication is that the spread of modern human behavior must have been cultural, at least in part. Based on the genetic dates, it cannot be the case of a single population that developed modern human behavior spread all around the world replacing the other humans who already lived there."

In examining the ancient Siberian's ancestry, Fu found about 2.3 percent of his DNA came from Neanderthals. That is a bit higher than found in modern humans living outside Africa today—a level that ranges from 1.7 to 2.1 percent—but too small a difference to be statistically significant, Fu said. Her findings on the date of human-Neanderthal mixing dramatically narrowed the likely range to between 50,000 and 60,000 years ago, a much tighter window than the previous range of between 37,000 and 86,000 years ago.

"It's like going up close to something with a camera," Reich said of getting high-quality data from a specimen this old. "You just get a much better picture. … You can see big bits of Neanderthal ancestry not yet digested by the process of human biology."

The ancient Siberian's DNA also contained pieces of Neanderthal DNA that were longer than researchers expected. DNA contributed from any individual is broken into smaller pieces with each passing generation during the normal mixing of maternal and paternal genetic material. The longer stretches of Neanderthal material, Reich and Fu said, may be the signature of mixing between Neanderthals and the ancestors of the Siberian individual within a few dozen generations of when he lived, though additional research is needed to ascertain that.

"There are lots of potential confounders, so we wanted to be conservative," Fu said. "Even if we cannot be sure of whether all the interbreeding occurred at once, the big picture is that we can be sure that the recent ancestors of this individual interbred with Neanderthals."

Explore further: Oldest DNA ever found sheds light on humans' global trek

More information: Genome sequence of a 45,000-year-old modern human from western Siberia, Nature, 514, 445–449 (23 October 2014) DOI: 10.1038/nature13810

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viko_mx
1 / 5 (6) Oct 23, 2014
Why there are complex mechanisms in the cell that are fighting with mutations in DNA and whose task is to recover its correct sequence and integrity, if mutations are a major driver of evolution? Why the immune system attempts to destroy mutated cells which can not be repaired? How does of evolutionary perspective random change in one physical characteristic of the organism as the form or the size of the limb for example, requiring a synchronous change of other characteristics such as muscle shape, a blood and the nervous system, and changes in the brain in order to steer effectively modified limb? How does by accident new information is inserted in DNA and how can be created a new gene of nowhere at random? I know that programmers deepen seriously in to the logic of the programs they write and use him intelligence to achieve the task. I have not heard any of them to rely on free chance. DNA (or RNA at least) is also a utility (program) that manages the life of living organisms.
ViperSRT3g
5 / 5 (2) Oct 23, 2014
@viko_mx: If you are hinting at what I think you're hinting at, please explain why viruses mutate on a yearly basis resulting in an ebb and flow of virility. For instance the recent outbreak of Ebola. It's been around for a while, but only just recently became a major issue once again. It has flared up in the past before, but went away on its own without infecting the entirety of the human population.

Do you think someone was genetically engineering the virus to make it more or less contagious with each outbreak? Or is it merely by chance that it happens to mutate as no string of DNA/RNA will remain perfectly intact and undisturbed out in the environment?
viko_mx
1 / 5 (6) Oct 23, 2014
The mutations cаuse damage to DNA and lost or unnecessary duplication of informaton.Different strains of a certain virus is not caused by mutations. This is the natural state of all living species on Earth. They exist freely in nature, but at a certain combination of environmental factors, natural selection increases the amount of a certain strain over another. When changing these conditions another strain becomes dominant locally or globally. This is due to the embedded in DNA mechanisms for maintaining the biological diversity within species. People are born different even with the same parents whit exception of identical twins, and this is not due to mutations, but due to embedded in DNA functionality for maintaining biodiversity within the species and to allow rapid adaptation to light possible changes in the environment they inhabit. Every living organism has a specific purpose involved in complex bio balance in nature and genetic changes pose unexpected risks for bio balance.
Torbjorn_Larsson_OM
5 / 5 (5) Oct 23, 2014
Interesting note on the coastal route, though John Hawks claims over on his blog that the population is a dead end. So yes, not only coastal, but it could have been a prime route:

@viko_mx: I'm not certain if you are asking serious questions or just trying to ineffectually promote religious dogma that goes against accepted science.

In case you are asking, your basic ideas are wrong.

Evolution is not a process that concerns itself with "information" and the genome is not a "program". Evolution is the differential reproduction in a whole population. Now we happen to have heredity through a genome, and its behavior is like a recipe, it is highly dependent on the environment. Of course, because that is what the process works with. So the 'information' depends on and derives from the environment.

This is evolution 101, see e.g. Dawkins's books. I would give references, but since it is completely irrelevant to how biology works, I won't. Find a library.

[tbctd]
Torbjorn_Larsson_OM
5 / 5 (5) Oct 23, 2014
[ctd]

In sum, your questions and claims are known to be erroneous and won't sway anyone interested in science. They already know that it is completely bull.

I will also specifically point out a glaring confusion of yours: There is no 'purpose' in nature (or other barriers against speciation), as evidenced from physics to biology.

Purpose is a human social construct since this is the only area where science discover it (within social science), and each person has to decide it for himself.
viko_mx
1 / 5 (5) Oct 24, 2014
Science is the scene of a clash of diferent ideas and this is the natural way to progress. Not the area where to be taken dogmatically certain views.
DNA contains both genes which are the recipes for the synthesis of proteins and synchronization mechanisms that determine under what circumstances which genes must be activated and which must be deactivated. The control and sinchronization of biochemical processes in the cell is the majority of the set of DNA information. Therefore DNA can confidently be called a comprehensive program for maintaining living organisms. Every complex organism or mechanism is highly sensitive to functional and structural changes. A random change is more likely to damage it and to confuse the complex interactions between its components and functionally related structures than to give him new functionality and make it more attuned. Engineers know this very well and like to joke with the phrase "when something works do not change it."
tjchamberlain
5 / 5 (3) Oct 24, 2014
@viko:

You are right - a random change in the DNA is more likely to cause damage than add functionality, and this is exactly why the vast majority of mutations don't survive and are removed from the genome. What you seem to be ignoring though are the much smaller number of mutations that are irrelevant or beneficial or survival that *do* survive in the genome and hence cause the genetic diversity we see today. These "non-deleterous" mutations are what provide the ability to adapt to changing environments - random mutation *is* the "embedded in DNA functionality for maintaining biodiversity within the species and to allow rapid adaptation to light possible changes in the environment they inhabit" that you speak of above. If you really want to insist on an "intelligent designer" then consider that he/she included random DNA mutations as an integral part of the overall intelligent design - life certainly couldn't exist (not for very long anyway) without them.
viko_mx
1 / 5 (3) Oct 27, 2014
Assuming that 1% of all mutations have not expressed adverse effect, before the organisms can evolve will die from loss of functionality due to the other 99% of harmful mutations. You can not build a house, while if you put 1 brick, others pull down 99. Mathematics is a useful science when you need to distinguish effectively philosophical and speculative theories of reality in which we live. In fact we have genetic entropy or process of accumulation of random errors in the DNA of each generation, leading to a drop in the quality of the DNA with time due to the loss of information. This leads to a lower capacity and the vitality of human race against time. Immune system and the complex cell defense mechanisms are responsible to fight mutations and restoring normal consistency and integrity of the DNA, but not always successful in 100% of cases. Larger mutations are removed from the natural selection thus population returns to the original gene pool.
viko_mx
1 / 5 (3) Oct 27, 2014
However, over time the quality of the gene pool is falling, because smaller mutations that are passed on to future generations. This means that our distant ancestors were more developed mentally and physically.
tjchamberlain
5 / 5 (2) Oct 28, 2014
@viko
You seem to think new mutations occur and build up in individual living organisms, but no, we are talking about mutations that happen only once per individual at the point of conception. Each individual organism born with a mutuation either has children or doesn't, depending on whether the mutation is deleterous or not. If an individual successfully has grandchildren then the mutation continues into the wider gene pool, if not then the mutation disappears. Most disappear.

This leads to a population with a mix of non-deleterous mutations, allowing the population as a whole to adapt to changing environments - if a particular mutation becomes important in the future then carriers have more/healthier grandchildren and the mutation becomes the norm, and contrariwise if a mutation becomes dangerous it's carriers have less grandchildren and it disappears. What is an "error" and what is "quality" is determined by reproductive success and will change depending on the time and place.
viko_mx
1 / 5 (3) Oct 29, 2014
We are only interested in mutations in the DNA of germ cells before and after conception, which gradually accumulate with each generation and result to information lost in a human gene pool. Mutations in other cells can cause disease, but is not transmitted to the next generations. In fact mutations are not needed and are unfavorable. In DNA has built-in mechanisms for rapid adaptation to environment and maintenance of biodiversity but always within a species.
The most commonly occurring are point mutations. This is a random change in a single base pair in the DNA molecule, which may affect a particular gene, but can also affect timing or controlling structure in DNA. If this type of mutation affect a gene, it change the chemical composition of the protein, which is produced by this gene. The function of the protein depend on chemical composition as mutch as on its three-dimensional shape. This three-dimensional shape is obtained after the protein leaves the ribosome and enters...
viko_mx
1 / 5 (3) Oct 29, 2014
... the special molecular machines called chaperones. If it has one or more wrong amino acid in its cemical compositions, it will fold in 3d shape incorrectly. This makes it ineffective or useless, or even harmful to the body. If you heard of prions, that are improperly folded proteins that can cause serious illnesses. By the way correct folding of proteines is hard task even for super computers. Folding the standart protein with 100-150 amino acids is very heavy computational task.
Mutated proteins can not be useful, because in most of cases dozens of other mechanisms in the cell count of its original function and when it is compromised these mechanisms lose synchronization and efficiency, and some of them may be blocked. If the point mutation affected the controlling structure of DNA, it can confuse the work of more genes. In all cases, the mutation is not likely to cause positive changes in the cell. Therefore the cell has so complex mechanisms to combat mutations in DNА.
tjchamberlain
5 / 5 (2) Oct 29, 2014
@viko:
I suspect you are confused and we are in fact talking about the same thing... but perhaps you can explain what these "built-in mechanisms for rapid adaptation and maintenance of biodiversity" are if they are different to the accumulation of non-deleterous random mutations?

Also note that while "mutated proteins" are usually a problem and remove themselves from the gene pool (by preventing their carrier's from breeding successfully), a small number are not a problem and hang around in the carriers' decendants. Sometimes these non-deleterous mutated proteins can in fact be very useful, the mutated protein that gives some of us lactase persistence being a good example.
viko_mx
1 / 5 (3) Oct 29, 2014
Mechanisms to ensure rapid adaptation are recombination of genes from both parents at conception, and in later activate or deactivate certain genes in human DNA. These processes are well studied, but the mechanisms that govern them will still not well understood. A single gene can affect many other characteristics of the organism, but also a feature may depend on many different genes. The interaction between genes is so complex that scientists may never fully understand these complex connections. Therefore, mutations and so undesirable. Therefore, the practice of genetic modification of various organisms is not a good idea.
viko_mx
1 / 5 (3) Oct 29, 2014
Only organisms with severe mutations relative to other individuals in the group, which lead to various diseases, can not leave offspring. In their absence, individuals usually leave offspring despite mutations. Although great importance for the continuation of the family have random environmental factors that dominate natural selection regardless of the quality of the DNA of a specific individual. In summary, these processes have a clear trend over time the gene pool of the human race to lose a substantial part of the information and quality to diminish.
tjchamberlain
5 / 5 (1) Oct 29, 2014
"Recombination" yes, but recombination of what? The differing alleles in our DNA that recombination mixes up have all arisen via random mutations. How do you propose the different eye colours arose, or the different hair types, or lactase persistence, twitch muscle response etc. etc.? Recombination without random mutations would just be cloning.

One man's "lose" is another man's gain and the deciding judgement in terms of evolution is survival. Yes we may be fatter, less active or whatever etc.than our ancestors but we are also more intelligent and more social than ever before. Most importantly we are also *much* more successful than ever before, so while you can moan the loss of "information" in the DNA if you want, that's just a pessimistic viewpoint. What we've gained is so much more and our position as the most successful human civiilsation ever on the planet is the proof of that..... lets just hope it's given us enough to get us through the transition to sustainable energy.
viko_mx
1 / 5 (2) Oct 30, 2014
Random mutations are not desirable and necessary, and always lead to damaged genes. Recombination of genes or their alleles from both parents is a built-in mechanism in DNA. Even in an ideal environment without mutagenic factors this mechanism will provide bio diversity within species - all the various genotypes of the total gene pool and expresses phenotypes respectively. This common gene pool of a particular type is gradually damaged by mutations over time.
"One man's" lose "is another man's gain and the deciding judgement in terms of evolution is survival." This is the law of the jungle and is not suitable for intelligent human being. This is the most inefficient way of thinking and It is good only to justify injustice in society.
viko_mx
1 / 5 (3) Oct 30, 2014
We can not call ourselves smarter than our ancestors despite our technological superiority we have, thanks to the bright minds in the recent past and their free spirit of discovery, because have more social and economic problems of them. In nature, everything is in harmony and relationships based on mutual benefits. Only man use mistaken concept and not be guided by the principles of life. Therefore today's world is turned upside down. Roman empire looked happy just before its collapse. History as always repeats itself.
tjchamberlain
5 / 5 (2) Oct 30, 2014
You haven't answered the question - where do the "alleles", the "bio-diversity", the "various genotypes", the "total gene pool" and the "phenotypes" all come from if not from the accumulation of random mutations?

The first living organism splits into two identical copies of itself. The two copies do the same, as do those next 4 and so on and so on - all of them identical. Then somewhere in this ongoing process a random mutation happens in one of the copies and "bio-diversity" is born, eventually leading to all the varieties of life we see today - if it weren't for the random mutations in this process all life today would be identical copies of that first organism. That's what science says, what do *you* say about where all the various differences in DNA come from?

Unless you are going to argue that single celled organisms represent the absolute peak of terrestrial life, your "everything's getting worse" argument is going nowhere.

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