Neanderthal Genome Project - AbsoluteAstronomy.com

The Neanderthal genome project is a collaboration of scientists coordinated by the Max Planck Institute for Evolutionary Anthropology

Max Planck Institute for Evolutionary Anthropology

The Max Planck Institute for Evolutionary Anthropology is a research institute based in Leipzig, Germany, founded in 1997. It is part of the Max Planck Society network....

in Germany and 454 Life Sciences

454 Life Sciences

454 Life Sciences, is a biotechnology company based in Branford, Connecticut. It is a subsidiary of Roche, and specializes in high-throughput DNA sequencing.-History and Major Achievements:...

in the United States to sequence

DNA sequencing

DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....

the Neanderthal

Neanderthal

The Neanderthal is an extinct member of the Homo genus known from Pleistocene specimens found in Europe and parts of western and central Asia...

genome

Genome

In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

.

Founded in July 2006, the project published their results in the May 2010 journal Science
Science (journal)
Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....

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

Anatomically modern humans

The term anatomically modern humans in paleoanthropology refers to early individuals of Homo sapiens with an appearance consistent with the range of phenotypes in modern humans....

and presented evidence that elements of their genome remain in that of non-African modern humans.

Findings

At roughly 3.2 billion base pair

Base pair

In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

s, the Neanderthal

Neanderthal

The Neanderthal is an extinct member of the Homo genus known from Pleistocene specimens found in Europe and parts of western and central Asia...

genome

Genome

is about the size of the modern human genome

Human genome

The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...

. According to preliminary sequences, 99.7% of the base pairs of the modern human and Neanderthal genomes are identical, compared to humans sharing around 98.8% of base pairs with the chimpanzee

Chimpanzee

Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...

. (Other studies concerning the commonality between chimps and humans have modified the commonality of 98% to a commonality of only 94%, showing that the genetic gap between humans and chimps is bigger than originally thought.) The researchers recovered ancient DNA

Ancient DNA

Ancient DNA is DNA isolated from ancient specimens. It can be also loosely described as any DNA recovered from biological samples that have not been preserved specifically for later DNA analyses...

of Neanderthals by extracting the DNA from the femur

Femur

The femur , or thigh bone, is the most proximal bone of the leg in tetrapod vertebrates capable of walking or jumping, such as most land mammals, birds, many reptiles such as lizards, and amphibians such as frogs. In vertebrates with four legs such as dogs and horses, the femur is found only in...

bones of three 38,000-year-old female Neanderthal specimens from Vindija Cave

Vindija Cave

Vindija is a cave near the city of Varaždin, Croatia. It contains one of the best preserved remains of the Neanderthals in the world, found in 1974. It is estimated that the Neanderthal man lived there about 30,000 years ago....

, Croatia

Croatia

Croatia , officially the Republic of Croatia , is a unitary democratic parliamentary republic in Europe at the crossroads of the Mitteleuropa, the Balkans, and the Mediterranean. Its capital and largest city is Zagreb. The country is divided into 20 counties and the city of Zagreb. Croatia covers ...

, and other bones found in Spain, Russia, and Germany. Only about half a gram of the bone samples was required for the sequencing, but the project faced many difficulties, including the contamination of the samples by the bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

that had colonized the Neanderthal's body and humans who handled the bones at the excavation site and at the laboratory.

Additionally, in 2010, the announcement of the discovery and analysis of Mitochondrial DNA

Mitochondrial DNA

Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...

(mtDNA) from the Denisova hominin

Denisova hominin

Denisova hominins , or Denisovans, are Paleolithic-Era members of the genus Homo that may belong to a previously unknown species. In , scientists announced the discovery of a finger bone fragment of a juvenile female that lived about 41,000 years ago, found in Denisova Cave in Altai Krai, Russia, a...

in Siberia

Siberia

Siberia is an extensive region constituting almost all of Northern Asia. Comprising the central and eastern portion of the Russian Federation, it was part of the Soviet Union from its beginning, as its predecessor states, the Tsardom of Russia and the Russian Empire, conquered it during the 16th...

revealed that this specimen differs from that of modern humans by 385 bases (nucleotide

Nucleotide

Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

s) 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 chimpanzee

Chimpanzee

Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...

s and modern humans is approximately 1,462 mtDNA base pairs. Analysis of the specimen's nuclear DNA

Nuclear DNA

Nuclear DNA, nuclear deoxyribonucleic acid , is DNA contained within a nucleus of eukaryotic organisms. In mammals and vertebrates, nuclear DNA encodes more of the genome than the mitochondrial DNA and is composed of information inherited from two parents, one male, and one female, rather than...

is under way and is expected to clarify whether the find is a distinct species. Even though the Denisova hominin's mtDNA lineage predates the divergence of modern humans and Neanderthals, coalescent theory

Coalescent theory

In genetics, coalescent theory is a retrospective model of population genetics. It attempts to trace all alleles of a gene shared by all members of a population to a single ancestral copy, known as the most recent common ancestor...

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, and Noonan et al. in Science. The results were received with some criticism, mainly surrounding the issue of a possible admixture of Neanderthals into the modern human genome. The speech-related gene FOXP2

FOXP2

Forkhead box protein P2 also known as FOXP2 is a protein that in humans is encoded by the FOXP2 gene, located on human chromosome 7 . FOXP2 orthologs have also been identified in all mammals for which complete genome data are available...

with the same mutations as in modern humans was discovered in ancient DNA in the El Sidrón

Sidrón Cave

The Sidrón Cave is an ancient cave in Piloña municipality, Asturias, northwestern Spain, where Paleolithic rock art and Neanderthal remains have been found. It is approximately 600 meters in length....

1253 and 1351c specimens, suggesting Neanderthals might have shared some basic language capabilities with modern humans.
In 2006, Richard Green's team had used a then new sequencing

DNA sequencing

DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....

technique developed by 454 Life Sciences that amplifies single molecules for characterization and obtained over a quarter-million unique short sequences ("reads"). The technique delivers randomly located reads, so that sequences of interest, e.g. 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 sample must be destructively sequenced.

Noonan et al., led by Edward Rubin

Edward Rubin

Edward M. "Eddy" Rubin is an internationally known geneticist and medical researcher at the Lawrence Berkeley National Laboratory in Berkeley, California and has served as the director of the Department of Energy's Joint Genome Institute since 2002...

, 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

Metagenomics

Metagenomics is the study of metagenomes, genetic material recovered directly from environmental samples. The broad field may also be referred to as environmental genomics, ecogenomics or community genomics. Traditional microbiology and microbial genome sequencing rely upon cultivated clonal cultures...

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.

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.

The publication by Noonan et al. 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

Most recent common ancestor

In genetics, the most recent common ancestor of any set of organisms is the most recent individual from which all organisms in the group are directly descended...

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).

Earlier mitochondrial DNA research led by 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 (~500k) 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:
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 geneticist Svante Pääbo

Svante Pääbo

Svante Pääbo is a Swedish biologist specializing in evolutionary genetics. He was born in 1955 in Stockholm to Sune Bergström, who shared the Nobel Prize in Physiology or Medicine with Bengt I. Samuelsson and John R. Vane in 1982, and his mother, Estonian Karin Pääbo.He earned his PhD from Uppsala...

, announced that they had completed the first draft of the Neanderthal genome 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". New results suggested that some adult Neanderthals were lactose intolerant

Lactose intolerance

Lactose intolerance, also called lactase deficiency or hypolactasia, is the inability to digest and metabolize lactose, a sugar found in milk...

. On the question of potentially cloning

Cloning

Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...

a Neanderthal, Pääbo commented, "Starting from the DNA extracted from a fossil, it is and will remain impossible."

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. However, this finding is disputed because of the lack of archeological evidence supporting their statement. The fossil evidence does not place Neanderthals and modern humans in close proximity at this time and place.

Previously, in 1999, a report was made of a rib fragment from the partial skeleton of a Neanderthal infant found in the Mezmaiskaya cave

Mezmaiskaya cave

Mezmaiskaya Cave is a cave at 44° 10' N 40° 00' E overlooking the right bank of the Sukhoi Kurdzhips in the southern Russian Republic of Adygea, located in the northwestern foothills of the Caucasus Mountains. Preliminary excavations recovered Mousterian artefacts, dated to about 35,000 B.P. and...

in the northwestern foothills of the Caucasus Mountains

Caucasus Mountains

The Caucasus Mountains is a mountain system in Eurasia between the Black Sea and the Caspian Sea in the Caucasus region .The Caucasus Mountains includes:* the Greater Caucasus Mountain Range and* the Lesser Caucasus Mountains....

that was radiocarbon-dated to 29,195 ± 965 B.P.

Before Present

Before Present years is a time scale used in archaeology, geology, and other scientific disciplines to specify when events in the past occurred. Because the "present" time changes, standard practice is to use AD 1950 as the origin of the age scale, reflecting the fact that radiocarbon...

, and therefore belonging to the latest lived Neanderthals. Ancient DNA

Ancient DNA

Ancient DNA is DNA isolated from ancient specimens. It can be also loosely described as any DNA recovered from biological samples that have not been preserved specifically for later DNA analyses...

was recovered for a mtDNA sequence showing 3.48% divergence from that of the Feldhofer Neanderthal

Kleine Feldhofer Grotte

Kleine Feldhofer Grotte was a cave, a paleoanthropologic site in the Neandertal Valley in northern Germany. In 1856, 60 Neanderthal specimens were unearthed from the cave...

, some 2,500 km to the west in Germany. Phylogenetic analysis placed the two in a clade

Clade

A clade is a group consisting of a species and all its descendants. In the terms of biological systematics, a clade is a single "branch" on the "tree of life". The idea that such a "natural group" of organisms should be grouped together and given a taxonomic name is central to biological...

distinct from modern humans, suggesting that their mtDNA types have not contributed to the modern human mtDNA pool.

Criticism

A 2007 review of the data by Wall and Kim reanalyses the data obtained from the published papers of Noonan et al. and Green et al., and it holds that the results are inconsistent with each other. The review proposes serious problems with the data quality in one of the studies, possibly due to modern human DNA contaminants and/or a high rate of sequencing errors.

The reanalyses confirmed both results to the Human-Neanderthal DNA Sequence Divergence Time (common ancestor), that is 706 kya (thousands of years ago) to the Noonan et al. analysis and 516 kya to the Green et al. analysis. The modern European-Neanderthal population split time was estimated at 35 kya for the Green et al. data, and 325 kya for the Noonan et al. data. Before, no split time was estimated by the Green et al. study, and according to Wall and Kim the split time originally estimated by Noonan et al. was even higher: 440 kya (the Noonan et al. paper mentions 370 kya).

While Noonan et al. were unable to definitively conclude that interbreeding between the two species of humans did not occur, they proclaim little likelihood of it having occurred at any appreciable level. The study opts for a 0% contribution of Neanderthal DNA to the modern European gene pool

Gene pool

In population genetics, a gene pool is the complete set of unique alleles in a species or population.- Description :A large gene pool indicates extensive genetic diversity, which is associated with robust populations that can survive bouts of intense selection...

, based on the 95% confidence interval that indicates a margin between 0% and 20% contribution. The reanalyses of Wall and Kim yielded interbreeding margins between 0% and 39% to the data of Noonan et al., and margins between 81% and 100% to the data of Green et al. These vastly inconsistent results could only be reconciled by assuming a very recent split time between the two populations of 60 kya or less. However, such a recent split time would not be consistent with the estimated modern European-Neanderthal population split time from the Noonan et al. data.

The key assumption of Noonan et al. is that the 38,000 years of fossil

Fossil

Fossils are the preserved remains or traces of animals , plants, and other organisms from the remote past...

isation suffered by the Neanderthal DNA should have the genome

Genome

analysis focus on ancient DNA

Ancient DNA

Ancient DNA is DNA isolated from ancient specimens. It can be also loosely described as any DNA recovered from biological samples that have not been preserved specifically for later DNA analyses...

fragments of about 50 to 70 base pairs in length. Green et al. do not make such an assumption; they generalized towards the exclusion of modern human nuclear DNA contamination by finding little evidence of modern human DNA contamination. Such mitochondrial DNA tends to remain preserved longer than nuclear DNA. However, Wall and Kim noted a length dependence of the results, having the small fragments pointing to a divergence time similar to the results of Noonan et al. and the large fragments much more similar on average to modern human DNA - even to the extent of indicating an estimated human-Neanderthal sequence divergence time that is less than the estimated divergence time of two extant members of one referenced population in West Africa. Although Wall and Kim hold modern human contamination to be size-biased, since Neanderthal DNA would be expected to have a tendency to be degraded into short fragments, they noted that length dependence of the results means that alignment issues alone are unlikely to be a sufficient explanation, since longer fragments would be easier to align and thus the data from longer fragments should be more accurate. Still they mark this as a signal of potential contamination in the data of Green et al. No similar signal of potential contamination was found in the data of Noonan et al.

Contamination in the data of Green et al. should have decreased the Neanderthal-specific sequence divergence in this study. Since this is not the case, the assumption of contamination also would indicate a higher sequencing error rate in the Green et al. data, since sequence errors would look the same as Neanderthal-specific mutations. These Neanderthal-specific mutations already were considered prone to error due to post-mortem DNA damage in both studies, and were excluded from the results.

In summary, Wall and Kim consider a model with 78% contamination more likely than a model with no contamination and 94% admixture.

A 2009 Green paper addresses some of the criticism.

External links

"The Neandertal Genome Project Website"
"Genetic algorithm model shows that modern humans out-competed the Neanderthal" Short summary of a peer review paper 2008
"Last of the Neanderthals" National Geographic, October 2008
MSNBC "Neanderthal genome project launches" 22 November 2006.
BBC News Paul Rincon, "Neanderthal DNA secrets unlocked" 15 November 2006
"Welcome to Neanderthal genomics" 17 November 2006
"Neanderthal Genome Sequencing Yields Surprising Results and Opens a New Door to Future Studies" 15 November 2006

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.

Findings

History

Criticism

See also

External links