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Neanderthal genome project

From Wikipedia, the free encyclopedia

The Neanderthal genome project is an effort of a group of scientists to sequence the Neanderthal genome.

It is coordinated by the Max Planck Institute for Evolutionary Anthropology in Germany, and was initiated by 454 Life Sciences, a biotechnology company based in Branford, Connecticut in the United States. Founded in July 2006, the project published their results in the May 2010 journal Science detailing an initial draft of the Neanderthal genome based on the analysis of four billion base pairs of Neanderthal DNA. The study determined that some mixture of genes occurred between Neanderthals and anatomically modern humans and presented evidence that elements of their genome remain in that of modern humans outside Africa.[1][2][3]

In December 2013, scientists reported, for the first time, a high coverage genome of a Neanderthal. The genome was extracted from the bone fragment of a Neanderthal female from around 50,000–100,000 years ago, found in a cave in the Altai mountains of Siberia.[4][5]

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  • The Neanderthal Genome Project
  • CARTA: DNA–Neandertal and Denisovan Genomes;Neandertal Genes in Humans;Neandertal Interbreeding
  • Population Genetics of the Neanderthal Genome Project
  • What Neanderthal DNA Is Doing To Your Genome
  • Neandertal genome confirms they were human

Transcription

I'm Dave Micklos of Cold Spring Harbor Laboratory. I'm here with Svante Paabo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and we're talking about Neanderthal and genetics. Welcome Dr. Paabo. Thank you. So who was Neanderthal and why are people so interested in him? Well, so Neanderthals were a group of humans that existed in western Asia and Europe until they became extinct around 30,000 years ago, and they are fascinating I think because they are truly our closest evolutionary relatives; no other organism is as closely related to humans today as they were. So it's very fascinating to compare us to them, because we can then really look at what is it that makes us unique compared to everyone else on this planet. And you are now involved in sequencing the entire set of genetic instructions of Neanderthal. And what will those exact instructions, its genome, tell us about us? So far we have the human genome, our own genome, and we have the genome of the Chimpanzee, our closest living relative. So we could then find all the changes and all the features in our genome that have changed on the evolutionary linear chart since we shared a common ancestor with the chimps. But that was quite a long time ago; say 5 to 7 million years ago, when we'll now have the genome of our closest relatives, of the Neanderthal, we will be able to say "what changed in the last little bit of human evolution; the last 300 -- 400 thousand years, when fully modern humans appeared for the first time?" So these are then guys with skeletons that are indistinguishable from ours, and among those genetic changes we hope that there will lay hints about what sets us apart, the things that made human technology possible, that made art possible, that made it possible for us to colonize the entire planet. Now the first human genome took us 15 years to accomplish; how long do you think it will take to accomplish the Neanderthal genome, and where are you in that process? So at the moment where we are we've worked 2 years seriously on this, and we have a first very rough draft of the genome so we can get the first overview; at the moment we are at the point where we have seen around 65% of the Neanderthal genome at least once, so we can sort of make windows and go over the Neanderthal chromosome and at least see more than half of the genetic information that is there. And we hope that within the next two years we will actually have almost all of the genetic information. Now you mentioned that you would like to see how we are similar or different to Neanderthal and similar or different to chimps. Could you give us an example of a gene that we share with Neanderthal but that we do not share the same variation with chimps? So one gene that we have been particularly interested since a long time [ago] actually is a gene called FOXP2, and that's the only individual gene that we know of today that has to do with language and speech ability in humans. And we know that because if we have a mutation in a human that knocks out one copy of this gene that we got from our mom or our dad, then we have a severe language problem or a speech problem, primarily about articulation, actually muscle control in the mouth and in the throat when we speak. And this gene is interesting because it has two changes in the protein it encodes that is specifically humans, that you see in no other apes or monkeys. So we were very interested in looking at Neanderthals and seeing if this is something unique to modern humans or not and somewhat to our surprise actually, it turned out that we share this with Neanderthals; Neanderthals look just like us with respect to this genetic change. So that then suggests that at least from the very little that we know about speech, there is no reason to assume that they couldn't articulate in speech as we do; that said of course, there are lots of genes there to test to do with speech that we don't know yet where they could have differences, but from the very tiny little thing we know today there is no reason to assume they weren't like us. Now your first experiment, which you did more than 10 years ago with Neanderthal DNA, worked with the mitochondrial chromosome, a very small chromosome. Why did you choose that to work with initially? So the mitochondrial DNA is particularly useful because it exists in many, many copies per cell, and in every cell we have for a typical nuclear gene just two copies; one from our mom and one from our dad. [With] the mitochondrial DNA we have several hundred or even thousands of copies per cell, and they all come from our mother, but it's easier to retrieve in an ancient specimen just because there are more copies there. It also gives a picture that's easier to interpret of our genetic history, since as it's inherited only though the maternal side; my mother, my grandmother, my great grandmother; it can trace female history back in a very easy way. But it's of course just a tiny part of our entire genetic makeup, so now it's fascinating to be looking all over the genome. Now that initial experiment was important, and what did that experiment tell us that was really pretty critical? So what it showed was that for this part of our genome, for the mitochondrial genome, the Neanderthals fall outside our variation. So where as all humans on the planet, in their mitochondrial DNA, trace their ancestry back to a common ancestor between a hundred and two hundred thousand years ago, the Neanderthal lineage goes back something like half a million years or a bit more, so this also showed that the Neanderthals then did not contribute any mitochondrial DNA to us today. So there was no indication that we mixed when we met from the mitochondrial DNA; now of course we are in the process of analyzing the entire nuclear genome and we might be able to pick up even a small contribution that may have happened, so in just a month or two I think we will be able to say much more about this. Now of course what you're touching on is sex; people are always interested in sex, and the question is during the time we spent together in Europe about 30,000 years ago, our ancestors and Neanderthals, did we ever mix it up, and it's an open question but do you think we'll be able to answer that question with certainty once we have the whole sequence? As a geneticist what I am really interested in [is] did one have children back then, and did those children contribute to our variation today; I'm sure in a way that they had sex, but what I am interested in was it productive in the sense, giving offspring that contributed to us. And that I think we will be able to answer quite rigorously with the genome sequence we will have. Now you followed up on your earlier work with the mitochondrial chromosome by sequencing the entire mitochondrial chromosome from 5 or 6 individuals; that was just within the last year. What did that experiment tell you? So what we can then do is start studying how much variation there is among Neanderthals genetically in the mitochondrial genome, and compare that to what we find in people living today to get a perspective; was it a lot of variation or was it little variation. And one fascinating thing in human variation is that when we compare ourselves to our closest living relatives, the great apes, we have quite little genetic variation which reflects if we go back to the rather small population in Africa that expanded around 100 thousand years ago. Now a big question was "Are the Neanderthals like the apes in having a lot of variation or like us in having little variation?" And the answer is very clear; they were like us in having little variations, and in fact the variations seem to be more on the scale of Europeans or Asians today rather than humans worldwide. So it suggests that they, also just like us, probably have a history where they went through bottlenecks where there were few individuals around that then expanded again and had more offspring; perhaps as a result of glaciations, they survived through at least three ice-ages. Well one final question; once you have the whole Neanderthal sequence, would it be technically feasible to recreate a Neanderthal in the flesh? Of course this is Jurassic Park, but maybe a little easier. I mean, you can of course speculate about technology that we don't even have today, where one would say in theory now, hypothetically, you would take a human embryo and replace thousands and thousands of genetic variants and create a Neanderthal. Perhaps in a science fiction novel you could imagine that; it's also quite clear that it would be ethically, totally indefensible to do something like that. You would create a human being simply to satisfy your scientific curiosity which is not something any responsible person would contemplate I think. Well thank you so much for being with us today. It was a pleasure.

Contents

Findings

According to preliminary sequences, 99.7% of the nucleotide sequences of the modern human and Neanderthal genomes are identical, compared to humans sharing around 98.8% of sequences with the chimpanzee.[6] (For some time, studies concerning the commonality between chimps and humans modified the commonality of 99% to a commonality of only 94%, showing that the genetic gap between humans and chimps was far larger than originally thought,[7][8] but more recent knowledge states the difference between humans, chimpanzees, and bonobos at just about 1.0%–1.2% again.[9][10])

The researchers recovered ancient DNA of Neanderthals by extracting the DNA from the femur bones of three 38,000 year-old female Neanderthal specimens from Vindija Cave, Croatia, and other bones found in Spain, Russia, and Germany.[11] Only about half a gram of the bone samples (or 21 samples each 50–100 mg[1]) was required for the sequencing, but the project faced many difficulties, including the contamination of the samples by the bacteria that had colonized the Neanderthal's body and humans who handled the bones at the excavation site and at the laboratory.[12]

Additionally, in 2010, the announcement of the discovery and analysis of Mitochondrial DNA (mtDNA) from the Denisova hominin in Siberia revealed that this specimen differs from that of modern humans by 385 bases (nucleotides) in the mtDNA strand out of approximately 16,500, whereas the difference between modern humans and Neanderthals is around 202 bases. In contrast, the difference between chimpanzees and modern humans is approximately 1,462 mtDNA base pairs. Analysis of the specimen's nuclear DNA is under way and is expected to clarify whether the find is a distinct species.[13][14] Even though the Denisova hominin's mtDNA lineage predates the divergence of modern humans and Neanderthals, coalescent theory does not preclude a more recent divergence date for her nuclear DNA.

History

In 2006, two research teams working on the same Neanderthal sample published their results, Richard Green and his team in Nature,[15] and Noonan's team in Science.[16] The results were received with some criticism, mainly surrounding the issue of a possible admixture of Neanderthals into the modern human genome.[17] The speech-related gene FOXP2 with the same mutations as in modern humans was discovered in ancient DNA in the El Sidrón 1253 and 1351c specimens,[18] suggesting Neanderthals might have shared some basic language capabilities with modern humans.[19]

 Svante Pääbo, director of the Department of Genetics at the Max Planck Institute for Evolutionary Anthropology and head of its Neanderthal genome project.
Svante Pääbo, director of the Department of Genetics at the Max Planck Institute for Evolutionary Anthropology and head of its Neanderthal genome project.

In 2006, Richard Green's team had used a then new sequencing technique developed by 454 Life Sciences that amplifies single molecules for characterization and obtained over a quarter of a million unique short sequences ("reads"). The technique delivers randomly located reads, so that sequences of interest – genes that differ between modern humans and Neanderthals – show up at random as well. However, this form of direct sequencing destroys the original sample so to obtain new reads more samples must be destructively sequenced.[20]

Noonan's team, led by Edward Rubin, used a different technique, one in which the Neanderthal DNA is inserted into bacteria, which make multiple copies of a single fragment. They demonstrated that Neanderthal genomic sequences can be recovered using a metagenomic library-based approach. All of the DNA in the sample is "immortalized" into metagenomic libraries. A DNA fragment is selected, then propagated in microbes. The Neanderthal DNA can be sequenced or specific sequences can be studied.[clarification needed][20]

Overall, their results were remarkably similar. One group suggested there was a hint of mixing between human and Neanderthal genomes, while the other found none, but both teams recognized that the data set was not large enough to give a definitive answer.[17]

The publication by Noonan, and his team revealed Neanderthal DNA sequences matching chimpanzee DNA, but not modern human DNA, at multiple locations, thus enabling the first accurate calculation of the date of the most recent common ancestor of H. sapiens and H. neanderthalensis. The research team estimates the most recent common ancestor of their H. neanderthalensis samples and their H. sapiens reference sequence lived 706,000 years ago (divergence time), estimating the separation of the human and Neanderthal ancestral populations to 370,000 years ago (split time).

"Our analyses suggest that on average the Neanderthal genomic sequence we obtained and the reference human genome sequence share a most recent common ancestor ~706,000 years ago, and that the human and Neanderthal ancestral populations split ~370,000 years ago, before the emergence of anatomically modern humans."

— Noonan et al. (2006)[16]

Earlier mitochondrial DNA research led by geneticist Svante Pääbo in 1997 had indicated present day Homo sapiens and Neanderthals mtDNA split into separate lineages approximately 500,000 years ago.

Green et al. calculated a divergence time of 516,000 years ago and do not indicate a split, while they claim the average divergence time between alleles within humans is thus 459,000 years with a 95% confidence interval between 419,000 and 498,000 years. These two dates (both ~500,000) were calculated with assumption on non-selective pressure. If positive selection forced mtDNA changes then the split time may be shorter. In this study, the team stated:

"Neanderthal genetic differences to humans must therefore be interpreted within the context of human diversity."

On the other hand, Noonan et al. found no evidence of Neanderthal admixture to the modern human genome, but they did not preclude admixture of up to 20% with a certainty better than 95%, and hence did not claim to present a definite answer to the question.

In February 2009, the Max Planck Institute's team led by Pääbo, announced that they had completed the first draft of the Neanderthal genome.[12] An early analysis of the data suggested in "the genome of Neanderthals, a human species driven to extinction" "no significant trace of Neanderthal genes in modern humans".[21] New results suggested that some adult Neanderthals were lactose intolerant.[19] On the question of potentially cloning a Neanderthal, Pääbo commented, "Starting from the DNA extracted from a fossil, it is and will remain impossible."[12]

In May 2010, the project released a draft of their report on the sequenced Neanderthal genome. Contradicting the results discovered while examining mitochondrial DNA, they demonstrated a range of genetic contribution to non-African modern humans ranging from 1% to 4%. From their Homo sapiens samples in Eurasia (French, Han Chinese & Papuan) the authors state that it is likely that interbreeding occurred in the Levant before Homo sapiens migrated into Europe.[22] However, this finding is disputed because of the paucity of archeological evidence supporting their statement. The fossil evidence does not conclusively place Neanderthals and modern humans in close proximity at this time and place.[23] In 2015, Israel Hershkovitz of Tel Aviv University reported that a skull found in a cave in northern Israel, is "probably a woman, who lived and died in the region about 55,000 years ago, placing modern humans there and then for the first time ever"[24] and pointing to a potential time and location when modern humans first interbred with Neanderthals.

Previously, in 1999, a report was made of a rib fragment from the partial skeleton of a Neanderthal infant found in the Mezmaiskaya cave in the northwestern foothills of the Caucasus Mountains that was radiocarbon-dated to 29,195±965 B.P., and therefore belonging to the latest lived Neanderthals. Ancient DNA was recovered for a mtDNA sequence showing 3.48% divergence from that of the Feldhofer Neanderthal, some 2,500 km to the west in Germany. Phylogenetic analysis placed the two in a clade distinct from modern humans, suggesting that their mtDNA types have not contributed to the modern human mtDNA pool.[25]

See also

General:

References

  1. ^ a b Green RE, Krause J, Briggs AW, et al. (May 2010). "A draft sequence of the Neandertal genome" (PDF). Science. 328 (5979): 710–722. PMID 20448178. doi:10.1126/science.1188021. 
  2. ^ The Neanderthal in Us
  3. ^ "Neandertal DNA may raise risk for some modern human diseases". Science News. Retrieved 2016-02-15. 
  4. ^ Zimmer, Carl (18 December 2013). "Toe Fossil Provides Complete Neanderthal Genome". New York Times. Retrieved 18 December 2013. 
  5. ^ Prüfer, Kay et al. (18 December 2013). "The complete genome sequence of a Neanderthal from the Altai Mountains". Nature. 505: 43–49. Bibcode:2014Natur.505...43P. PMC 4031459Freely accessible. PMID 24352235. doi:10.1038/nature12886. Retrieved 18 December 2013. 
  6. ^ Than, Ker (6 May 2010). "Neanderthals, Humans Interbred—First Solid DNA Evidence". National Geographic Society. Retrieved 9 May 2010. 
  7. ^ Cohen, Jon (29 June 2007). "Relative Differences: The Myth of 1%" (PDF). AAAS. 
  8. ^ "Humans and Chimps: Close But Not That Close". Scientific American. 2006-12-19. Retrieved 2006-12-20. 
  9. ^ Wong, Kate (1 September 2014). "Tiny Genetic Differences between Humans and Other Primates Pervade the Genome". Scientific American. Retrieved 12 October 2016. 
  10. ^ Gibbons, Ann (13 June 2012). "Bonobos Join Chimps as Closest Human Relatives". Science/AAAS. 
  11. ^ "Scientists Decode Majority of Neanderthal Man's Genome". Deutsche Welle. 13 February 2009. 
  12. ^ a b c McGroarty, Patrick (12 February 2009). "Team in Germany maps Neanderthal genome". The Associated Press. 
  13. ^ Brown, David (March 25, 2010). "DNA from bone shows new human forerunner, and raises array of questions". Washington Post. 
  14. ^ Krause J, Fu Q, Good JM, et al. (April 2010). "The complete mitochondrial DNA genome of an unknown hominin from southern Siberia". Nature. 464 (7290): 894–897. PMID 20336068. doi:10.1038/nature08976. 
  15. ^ Green, Richard E.; et al. (16 November 2006). "Analysis of one million base pairs of Neanderthal DNA" (PDF). Nature. 444 (7117): 330–336. PMID 17108958. doi:10.1038/nature05336. 
  16. ^ a b Noonan, James P.; et al. (17 November 2006). "Sequencing and Analysis of Neanderthal Genomic DNA" (PDF). Science. 314 (5802): 1113–1118. PMC 2583069Freely accessible. PMID 17110569. doi:10.1126/science.1131412. 
  17. ^ a b Timmer, John (2006-11-17). "Welcome to Neanderthal genomics". 
  18. ^ Krause J, Lalueza-Fox C, Orlando L, et al. (November 2007). "The derived FOXP2 variant of modern humans was shared with Neandertals". Curr. Biol. 17 (21): 1908–1912. PMID 17949978. doi:10.1016/j.cub.2007.10.008. 
  19. ^ a b Inman, Mason (12 February 2009). "Neanderthal Genome "First Draft" Unveiled". National Geographic News. 
  20. ^ a b Lynn Yarris (15 November 2006). "Neanderthal Genome Sequencing Yields Surprising Results and Opens a New Door to Future Studies". Lawrence Berkeley National Laboratory. Retrieved 2009-02-16. 
  21. ^ Wade, Nicholas (12 February 2009). "Scientists in Germany Draft Neanderthal Genome". The New York Times. Retrieved 20 May 2010. 
  22. ^ "Draft full sequence of Neanderthal Genome". Science Mag. 7 May 2010. 
  23. ^ Wade, Nicholas (6 May 2010). "Signs of Neanderthals Mating With Humans". The New York Times. 
  24. ^ Skull discovery suggests location where humans first had sex with Neanderthals
  25. ^ Igor V. Ovchinnikov; Anders Götherström; Galina P. Romanova; Vitaliy M. Kharitonov; Kerstin Lidén; William Goodwin (30 March 2000). "Molecular analysis of Neanderthal DNA from the northern Caucasus". Letters to Nature. Nature 404. pp. 490–493. doi:10.1038/35006625. Retrieved 13 March 2011. 

Further reading

External links

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