A Draft Sequence of the Neandertal Genome

A Draft Sequence of the Neandertal Genome

Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.

To cut a long story short…

The authors suggest that non-Africans having about 1-4% Neanderthal ancestry is the most likely explanation for the variation in the DNA they have found. It’s not an absolute. A much less likely but not impossible scenarios is that the variation is due to population structure in Africa prior to the OOA, which may relate with the earlier separation of the ancestors of modern Africans and non-Africans inside Africa, although John Hawkes thinks this is so unlikely he was surprised they gave it space on the paper.

But, considering the number of genes in non Africans that have a time depth that is considerably older than the OOA movement (over 1 million years on one in one study by Hammer et al), and I think there is now decent evidence for Neanderthal ancestry in non-Africans.

I have some issues with the paper. Modern humans were in the near East about 120k ago, keeping company with Neanderthals for many millennia, but the interbreeding date comes out at 80,000 to 50,000 years. What were they doing with the rest of the time?

Such a scenario is compatible with the archaeological record, which shows that modern humans appeared in the Middle East before 100,000 years ago whereas the Neandertals existed in the same region after this time, probably until 50,000 years ago.

  And they observe that modern Europeans don’t seem to have a higher amount of Neanderthal ancestry than anyone else. But then they add:

 This possibility can be addressed by the determination of genome sequences from pre agricultural early modern humans in Europe (85). It is also possible that if the expansion of modern humans occurred differently in Europe than in the Middle East, for example by already large populations interacting with Neandertals, then there may be little or no trace of any gene flow in present-day Europeans even if interbreeding occurred.  

Which is what I suspect is more likely. I’d also like to address the apparent lack of modern human ancestry in the Neanderthals: well a quick look at the dates of the remains sampled; not younger than 38,000 BP. Which is prior to the date modern humans started to move into that part of Europe. Possibly a future investigation of later dated remains would show some AMH ancestry in them, as their appearance suugests they may be hybrids. I think the  Lagar Velho specimen would be a possible source, although it would be a pity to damage the specimen, possibly the Gorham’s Cave bones could yield relevant information.

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The lineage of King Tutankhamun from ancient DNA analysis

The news of the month, kindly posted to me by a friend, is that they have proved via ADNA that the mummy from tomb Kv55 is Akhenaten, son of Amenhotep III and king Tutankhamun’s father, and that the younger lady (KV35) is his mother. It also seems Tut died of malaria and suffered congenital deformities, which I’d guess were the result of incestuous marriages in the royal family. This means that the prior ageing of KV55 as 18 was way off.

This also mean that queen the red-haired queen Tiye (elder lady mummy) was the mother of Kv35 (using logic, they all have the same mt DNA), which might explain why they were found in the same tomb.

I’ve prepared a brief genealogy.

      

Known grandparents  

 Amenhotep III  and Tiye (whose parents were Tuya and Yuya)

        

Known parents

Akhenaten (Kv 55)  and  (KV 35).

The actual name of KV35 uncertain but she has been suggested as Nefertiti, these were brother and sister.

 

 Tutankhamun, who appears to have also married his sister Ankhesenamun.

It would be interesting to see if the mummy in Kv21A is indeed Tut’s wife Ankhesenamun, as she is known to be the daughter of Nefertiti and Akhenaten, and this could give a definitive answer as to whether Kv35 is in fact Nefertiti.  Ankhesenamun has been identified as the mother of one of the fetuses from Tut’s tomb, so this might be on the cards for the future.

Ancestry and Pathology in King Tutankhamun’s Family
Zahi Hawass, PhD; Yehia Z. Gad, MD; Somaia Ismail, PhD; Rabab Khairat, MSc; Dina Fathalla, MSc; Naglaa Hasan, MSc; Amal Ahmed, BPharm; Hisham Elleithy, MA; Markus Ball, MSc; Fawzi Gaballah, PhD; Sally Wasef, MSc; Mohamed Fateen, MD; Hany Amer, PhD; Paul Gostner, MD; Ashraf Selim, MD; Albert Zink, PhD; Carsten M. Pusch, PhD
JAMA. 2010;303(7):638-647.

Context

  The New Kingdom in ancient Egypt, comprising the 18th, 19th, and 20th dynasties, spanned the mid-16th to the early 11th centuries BC. The late 18th dynasty, which included the reigns of pharaohs Akhenaten and Tutankhamun, was an extraordinary time. The identification of a number of royal mummies from this era, the exact relationships between some members of the royal family, and possible illnesses and causes of death have been matters of debate.

Objectives

  To introduce a new approach to molecular and medical Egyptology, to determine familial relationships among 11 royal mummies of the New Kingdom, and to search for pathological features attributable to possible murder, consanguinity, inherited disorders, and infectious diseases.

Design

  From September 2007 to October 2009, royal mummies underwent detailed anthropological, radiological, and genetic studies as part of the King Tutankhamun Family Project. Mummies distinct from Tutankhamun’s immediate lineage served as the genetic and morphological reference. To authenticate DNA results, analytical steps were repeated and independently replicated in a second ancient DNA laboratory staffed by a separate group of personnel. Eleven royal mummies dating from circa 1410-1324 BC and suspected of being kindred of Tutankhamun and 5 royal mummies dating to an earlier period, circa 1550-1479 BC, were examined.

Main Outcome Measures

  Microsatellite-based haplotypes in the mummies, generational segregation of alleles within possible pedigree variants, and correlation of identified diseases with individual age, archeological evidence, and the written historical record.

Results

Genetic fingerprinting allowed the construction of a 5-generation pedigree of Tutankhamun’s immediate lineage. The KV55 mummy and KV35YL were identified as the parents of Tutankhamun. No signs of gynecomastia and craniosynostoses (eg, Antley-Bixler syndrome) or Marfan syndrome were found, but an accumulation of malformations in Tutankhamun’s family was evident. Several pathologies including Köhler disease II were diagnosed in Tutankhamun; none alone would have caused death. Genetic testing for STEVOR, AMA1, or MSP1 genes specific for Plasmodium falciparum revealed indications of malaria tropica in 4 mummies, including Tutankhamun’s. These results suggest avascular bone necrosis in conjunction with the malarial infection as the most likely cause of death in Tutankhamun. Walking impairment and malarial disease sustained by Tutankhamun is supported by the discovery of canes and an afterlife pharmacy in his tomb.

Conclusion  Using a multidisciplinary scientific approach, we showed the feasibility of gathering data on Pharaonic kinship and diseases and speculated about individual causes of death.

According to someone (not me) who has been bothered to enter the Y chr markers as seen on the video, Tut is coming up as R1b. I’d have put money on it being something more like an E1 Y chr, or maybe J as an outside chance…R1b isn’t unknown in Egypt, (see Wood 2005) but isn’t exactly common. R1b appears to have entered Africa from Asia sometime in the Neolithic along with Afro-Asiatic, which is really all I have to say until I get a published source and more detail. Can’t get any detail on the mt DNA, unfortunately. 

For anyone interested, there’s a bunch of videos at the Discovery Channel site about this, with some good shots of Akhenaten in his coffin.

mt DNA from La Palma Guanche remains

The maternal aborigine colonization of La Palma (Canary Islands)
Teeth from 38 aboriginal remains of La Palma (Canary Islands) were analyzed for external and endogenous mitochondrial DNA control region sequences and for diagnostic coding positions. Informative sequences were obtained from 30 individuals (78.9%). The majority of lineages (93%) were from West Eurasian origin, being the rest (7%) from sub-Saharan African ascription. The bulk of the aboriginal haplotypes had exact matches in North Africa (70%). However, the indigenous Canarian sub-type U6b1, also detected in La Palma, has not yet been found in North Africa, the cradle of the U6 expansion. The most abundant H1 clade in La Palma, defined by transition 16260, is also very rare in North Africa. This means that the exact region from which the ancestors of the Canarian aborigines came has not yet been sampled or that they have been replaced by later human migrations. The high gene diversity found in La Palma (95.22.3), which is one of the farthest islands from the African continent, is of the same level than the previously found in the central island of Tenerife (92.42.8). This is against the supposition that the islands were colonized from the continent by island hopping and posterior isolation. On the other hand, the great similarity found between the aboriginal populations of La Palma and Tenerife is against the idea of an island-by-island independent maritime colonization without secondary contacts. Our data better fit to an island model with frequent migrations between islands.

More ancient DNA from native North Africa, showing a mainly Eurasian origin for the mt DNA.  The standard result for all ancient North African ADNA.

Research on ancient DNA in the Near East

Research on ancient DNA in the Near East

An interesting read on the state of aDNA work in the near East. Of most interest was to me was the aDNA from the mummies at Dakleh Oasis.

To obtain the frequencies of these mtDNA types, amplification of the HVRI region and three RFLP markers was conducted. The authors succeeded in analysing RFLP markers in 34 samples and HVRI sequences in 18 of the samples. Both populations, ancient and contemporary, fit the north-south clinal distribution of “southern” and “northern” mtDNA types (Graver et al. 2001). However, significant differences were found between these populations. Based on an increased frequency of HpaI 3592 (+) haplotypes in the contemporary Dakhlehian population, the authors suggested that, since Roman times, gene flow from the Sub-Saharan region has affected gene frequencies of individuals from the oasis.

Which is from the Graver mummy DNA study, I believe. It actually suggests there’s more sub Saharan input  to the Egyptian population than anything else since the Roman era.

Mitochondrial DNA Research in the Dakhleh Oasis, Egypt
Alison M. Graver, Ryan L. Parr, Sandra Walters, Renée C. Praymak, Jennifer M. Maki and J.El Molto

Molecular genetic research is being conducted as part of the Dakhleh Oasis Project (DOP), an international and multi-disciplinary research initiative in the western desert of Egypt. Mitochondrial DNA (mtDNA) is being analyzed from both ancient human skeletal remains associated with the Roman period town of Kellis (100 to 450 AD) and contemporary inhabitants of the Dakhleh Oasis. The primary objectives of this research are to derive paleogenetic information about the inhabitants of ancient Kellis, and to develop a picture of change over time within this desert oasis. Preliminary mtDNA restriction site data and control region sequence variability suggest significant genetic differences exist between the ancient and modern oasis populations

It’s a good grounding in the state of aDNA at the moment, human, animal and pathogenic. Worth the read.

There’s also another pdf  with a lot of abstracts about ancient DNA from the 5th annual ancient DNA conference.

The maternal aborigine colonization of La Palma (Canary Islands)

The maternal aborigine colonization of La Palma (Canary Islands)

Teeth from 38 aboriginal remains of La Palma (Canary Islands) were analyzed for external and endogenous mitochondrial DNA control region sequences and for diagnostic coding positions. Informative sequences were obtained from 30 individuals (78.9%). The majority of lineages (93%) were from West Eurasian origin, being the rest (7%) from sub-Saharan African ascription. The bulk of the aboriginal haplotypes had exact matches in North Africa (70%). However, the indigenous Canarian sub-type U6b1, also detected in La Palma, has not yet been found in North Africa, the cradle of the U6 expansion. The most abundant H1 clade in La Palma, defined by transition 16260, is also very rare in North Africa. This means that the exact region from which the ancestors of the Canarian aborigines came has not yet been sampled or that they have been replaced by later human migrations. The high gene diversity found in La Palma (95.22.3), which is one of the farthest islands from the African continent, is of the same level than the previously found in the central island of Tenerife (92.42.8). This is against the supposition that the islands were colonized from the continent by island hopping and posterior isolation. On the other hand, the great similarity found between the aboriginal populations of La Palma and Tenerife is against the idea of an island-by-island independent maritime colonization without secondary contacts. Our data better fit to an island model with frequent migrations between islands.

Again the indigenous Canarians show up as mainly Eurasian/North African for ancestry. Not really a surprise that L lineages show up a little. Although a lot of them seem to be in North Africa from the slave trade, a couple are older and one shows an entry into Iberia about 20,000 years ago.

Neanderthal genome decoded

Link

Their lives may have been nasty, brutish and short but their DNA has survived long enough to be almost fully decoded in a pioneering study that has revealed just how closely related the Neanderthals were to modern humans.

For the first time scientists have deciphered the genetic sequence of the Neanderthal genome. It is the first genetic blueprint of an extinct human species and a tour de force in terms of the scientific techniques used to recover tiny strands of ancient DNA from fragments of fossilised bones tens of thousand of years old.

Although scientists are far from answering the many questions about the last of our relatives known to live alongside modern humans, they believe that the research is close to finding out what it is, genetically, that made us human.

Prof Svante Paabo of the Max Planck Institute for Evolutionary Anthropology in Leipzig was to reveal at the American Association for the Advancement of Science in Chicago this weekend that he and his colleagues had deciphered 60 percent of the Neanderthal genome and used it to calculate that the last common, ape-like ancestor of modern man and the Neanderthals lived about 830 000 years ago.

The project took more than two-and-a-half years of research on dozens of Neanderthal bones from 40 000-70 000 years old and excavated from four archaeological sites in Europe, stretching from southern Russia and Croatia to Germany and Spain.

They extracted enough DNA from an analysis of 70 fossilised bones to build up a library of Neanderthal DNA covering 3.7 billion “base pairs” – the individual letters of the genetic code – and in the process discovered that the extinct humans were very closely related to modern people.

“The Neanderthals are so closely related to us that they fall into our genetic variation,“ Paabo said. In other words, it would be difficult to distinguish Neanderthal DNA from the DNA of a modern European, Asian or African.

The last Neanderthals died out about 30,000 years after sharing the same European landscape with modern humans for many thousands of years.

It has been an enduring mystery as to why they disappeared and whether they ever interbred with their close human cousins – although the latest evidence from the DNA suggests they did not.

“What we have looked at, from the point of view of variation today, is the contribution from Neanderthals to the human gene pool. That was very little, if anything. Our data shows that, if there was a contribution, it was very small,” Paabo said.

“But the cool thing is that interbreeding was a two-way street. For the first time we can look at whether there was a contribution from human ancestors to Neanderthals because, for the first time, we have a Neanderthal genome,” he said.

Another question is whether Neanderthals could speak.

Although they are known to have a hyoid bone in the throat, which is anatomically important for articulating words, the only other evidence comes from an analysis of a gene called FOXP2, which is known to be critical to speech development in modern humans.

Paabo said that the Neanderthal FOXP2 gene shares two changes to its DNA sequence that is also seen in modern humans but not in chimpanzees. These two changes support the view that Neanderthals may have been able to communicate verbally.

Other insights gained from a preliminary analysis of the Neanderthal genome are that the species could not drink milk as adults – they have the same lactose intolerance seen in the majority of modern humans – and they also have a mutation in the gene involved in brain development seen in modern-day Africans.

Just a thought… if, as it says “The Neanderthals are so closely related to us that they fall into our genetic variation,” how did they come to the conclusion they didn’t contribute to the modern gene pool? Confused.

I have to point out here that the average North American is only about 4% native American, so any contribution from a nearly wiped out group can be just a trace; the same goes for the very ancient North Africans and Australoid South Americans, of whom no genetic trace has been found (modern humans).

The lactase-persistence-associated allele in early Neolithic Europeans

The lactase-persistence-associated allele in early Neolithic Europeans

Lactase persistence (LP), the dominant Mendelian trait conferring the ability to digest the milk sugar lactose in adults, has risen to high frequency in central and northern Europeans in the last 20,000 years. This trait is likely to have conferred a selective advantage in individuals who consume appreciable amounts of unfermented milk. Some have argued for the “culture-historical hypothesis,” whereby LP alleles were rare until the advent of dairying early in the Neolithic but then rose rapidly in frequency under natural selection. Others favor the “reverse cause hypothesis,” whereby dairying was adopted in populations with preadaptive high LP allele frequencies. Analysis based on the conservation of lactase gene haplotypes indicates a recent origin and high selection coefficients for LP, although it has not been possible to say whether early Neolithic European populations were lactase persistent at appreciable frequencies. We developed a stepwise strategy for obtaining reliable nuclear ancient DNA from ancient skeletons, based on (i) the selection of skeletons from archaeological sites that showed excellent biomolecular preservation, (ii) obtaining highly reproducible human mitochondrial DNA sequences, and (iii) reliable short tandem repeat (STR) genotypes from the same specimens. By applying this experimental strategy, we have obtained high-confidence LP-associated genotypes from eight Neolithic and one Mesolithic human remains, using a range of strict criteria for ancient DNA work. We did not observe the allele most commonly associated with LP in Europeans, thus providing evidence for the culture-historical hypothesis, and indicating that LP was rare in early European farmers.

Just an archived item- I’ve posted a news  item on this before but it’s nice to have the paper. The lactose tolerance seems to only about 8,000 years old, and has occured independantly in several different pastoralist groups around the world. I guess retention of a juvenille trait is an easy mutation for the genome to make. Last time I looked it was worked out on a computer simulation to have spread with the  Linearbandkeramik culture

Search for founder mitochondrial lineages in Holocene human remains in Patagonia

Search for founder mitochondrial lineages in Holocene human remains in Patagonia.
M. Moraga1, E. Aspillaga2, F. Mena3. 1Programa de Genética Humana, Facultad de Medicina, Universidad de Chile.
2Departamento de Antropología, Facultad de Ciencias Sociales, Universidad de Chile. 3Museo Chileno de Arte Precolombino.

The archeological register of Patagonia is extremely interesting; it has the oldest record of human occupation in America (Monte Verde, 14,500 BP). It also has many Holocene sites that contain human bones as old as 8,800 years BP. Due to the favorable environmental conditions (cold and dry), the conservation of human remains is good enough to allow obtaining mitochondrial DNA, and in exceptional cases, nuclear DNA. We extracted and amplified mitochondrial DNA sequences of samples from northern, central and southern Patagonia distributed in a temporal range from 8,800 to 400 years AP. The majority of the samples studied belonged to haplogroups C and D; in one proto- Kaweskar we found haplotype C (16318G), previously described in a historical Aonikenk. Haplotype D4h3 (16241G and 16342C), which is found in present Patagonian populations and was recently described in a skeleton of 10,300 years BP in Alaska was also found, reinforcing the hypothesis of a connection between the populations of Patagonia and the hunter-gatherers of the beginning of the Holocene. In northern Patagonia we also detected the presence of haplogroup B in two individuals from the early Holocene. This haplogroup had not been found in present-day populations south of 43 degrees south latitude. Finally, in the most recent samples (400 years BP) we found haplotype D (16187T), very common in current populations of southern Chile, suggesting a possible population movement between them.

More from todays pdf.

Ancient Jomon DNA from Hokkaido

Mitochondrial DNA analysis of the Jomon and Epi-Jomon individuals in Hokkaido, Japan.

American Journal of Physical Anthropology doi: 10.1002/ajpa.20923

N. Adachi1, K. Shinoda2, K. Umetsu3, Y. Dodo1. 1Department of Anatomy and Anthropology, Tohoku University School of
Medicine, 2Department of Anthropology, National Science Museum, Tokyo, 3Department of Experimental and Forensic
Pathology, Faculty of Medicine, Yamagata University.

From the morphological point of view, prehistoric populations in Hokkaido are considered to have been least influenced by Yayoi immigrants. Therefore, genetic study of these people can be expected to provide important information on the genealogy of the early settlers of the Japanese archipelago. In the present study, we examined the genealogy of the seventy-six Jomon and Epi-Jomon skeletons excavated in Hokkaido, Japan by mitochondrial DNA analysis. To identify their genealogy securely, we analyzed the coding region of mtDNA by using amplified product-length polymorphisms (Umetsu et al., 2001, 2005) and direct sequencing. We also sequenced the segments of two hypervariable regions of mtDNA, and  assigned the mtDNA under study to relevant haplogroups using the known mtDNA databases.

Haplogroups D4, G1, M7a, and N9b were observed in the individuals, and N9b was by far the most predominant. The requencies of the haplogroups were quite different from any modern populations including Ainu and Okinawans. Haplogroup N9b is hitherto observed almost only in Japanese populations; therefore, this  haplogroup might be the (pre-) Jomon contribution to the modern Japanese mtDNA pool.

I’m looking for something on this journal summary, so I’ll be posting a lot of abtracts from it today.More on ancient Jomon DNA.

Mitochondrial DNA analysis of Jomon skeletons from the Funadomari site, Hokkaido, and its implication for the origins of Native American 
 
Ancient DNA recovered from 16 Jomon skeletons excavated from Funadomari site, Hokkaido, Japan was analyzed to elucidate the genealogy of the early settlers of the Japanese archipelago. Both the control and coding regions of their mitochondrial DNA were analyzed in detail, and we could securely assign 14 mtDNAs to relevant haplogroups. Haplogroups D1a, M7a, and N9b were observed in these individuals, and N9b was by far the most predominant. The fact that haplogroups N9b and M7a were observed in Hokkaido Jomons bore out the hypothesis that these haplogroups are the (pre-) Jomon contribution to the modern Japanese mtDNA pool. Moreover, the fact that Hokkaido Jomons shared haplogroup D1 with Native Americans validates the hypothesized genetic affinity of the Jomon people to Native Americans, providing direct evidence for the genetic relationships between these populations. However, probably due to the small sample size or close consanguinity among the members of the site, the frequencies of the haplogroups in Funadomari skeletons were quite different from any modern populations, including Hokkaido Ainu, who have been regarded as the direct descendant of the Hokkaido Jomon people. It appears that the genetic study of ancient populations in northern part of Japan brings important information to the understanding of human migration in northeast Asia and America.

A preliminary analysis of the DNA and diet of the extinct Beothuk: A systematic approach to ancient human DNA

A preliminary analysis of the DNA and diet of the extinct Beothuk: A systematic approach to ancient human DNA

We have used a systematic protocol for extracting, quantitating, sexing and validating ancient human mitochondrial and nuclear DNA of one male and one female Beothuk, a Native American population from Newfoundland, which became extinct 180 years ago. They carried mtDNA haplotypes, which fall within haplogroups X and C, consistent with Northeastern Native populations today. In addition we have sexed the male using a novel-sexing assay and confirmed the authenticity of his Y chromosome with the presence of the Native American specific Y-QM3 single nucleotide polymorphism (SNP). This is the first ancient nuclear SNP typed from a Native population in the Americas. In addition, using the same teeth we conducted a stable isotopes analysis of collagen and dentine to show that both individuals relied on marine sources (fresh and salt water fish, seals) with no hierarchy seen between them, and that their water sources were pooled or stored water. Both mtDNA sequence data and Y SNP data hint at possible gene flow or a common ancestral population for both the Beothuk and the current day Mikmaq, but more importantly the data do not lend credence to the proposed idea that the Beothuk (specifically, Nonosabasut) were of admixed (European-Native American) descent. We also analyzed patterns of DNA damage in the clones of authentic mtDNA sequences; there is no tendency for DNA damage to occur preferentially at previously defined mutational hotspots, suggesting that such mutational hotspots are not hypervariable because they are more prone to damage.

This is a mt DNA analysis of chief Nonosabasut, and wife, Demasduit from Newfoundland. He was X2a, and she was C (Q-M3). I keep seeing Asia put down as the place of origin for X2a. Have I missed a paper? As far as I know X2 is limited to western Europe, the near east and the Saami.