Neanderthals and Cro-Magnon

I thought I knew most of the players in this subject (though I know two of the authors) but this came out of left field:The biggest problem with the entire debate is that a neanderthal that yields a sequence well within the distribution of human variation like the Cro-Magnon sequences these guys report, would be written off as a lab contamination....thus, the out of Africa guys have their answer before they even do the study....glad I work on mammoths..less controversy PNAS published May 12, 2003
Evolution
Evidence for a genetic discontinuity between Neandertals and 24,000-year-old anatomically modern EuropeansDavid Caramelli , Carles Lalueza-Fox , Cristiano Vernesi , Martina Lari , Antonella Casoli , Francesco Mallegni ||, Brunetto Chiarelli , Isabelle Dupanloup , Jaume Bertranpetit , Guido Barbujani , and Giorgio Bertorelle
Dipartimento di Biologia Animale e Genetica, Universit di Firenze, Via del Proconsolo 12, 50122 Florence, Italy; Departament de Biologia Animal, Universitat de Barcelona, Avenida Diagonal 645, 08028 Barcelona, Spain; Dipartimento di Biologia, Universit di Ferrara, via Borsari 46, 44100 Ferrara, Italy; Dipartimento di Chimica Generale e Inorganica, Chimica Analitica, Chimica Fisica, Universit di Parma, Parco Area delle Scienze 17/A, 43100 Parma, Italy; ||Dipartimento di Scienze Archeologiche, Universit di Pisa, via Galvani 1, 56100 Pisa, Italy; and Facultat de Cincies de la Salut i de la Vida, Universitat Pompeu Fabra, Doctor Aiguader 80, 08003 Barcelona, SpainDuring the late Pleistocene, early anatomically modern humans coexisted in Europe with the anatomically archaic Neandertals for some thousand years. Under the recent variants of the multiregional model of human evolution, modern and archaic forms were different but related populations within a single evolving species, and both have contributed to the gene pool of current humans. Conversely, the Out-of-Africa model considers the transition between Neandertals and anatomically modern humans as the result of a demographic replacement, and hence it predicts a genetic discontinuity between them. Following the most stringent current standards for validation of ancient DNA sequences, we typed the mtDNA hypervariable region I of two anatomically modern Homo sapiens sapiens individuals of the Cro-Magnon type dated at about 23 and 25 thousand years ago. Here we show that the mtDNAs of these individuals fall well within the range of variation of today's humans, but differ sharply from the available sequences of the chronologically closer Neandertals. This discontinuity is difficult to reconcile with the hypothesis that both Neandertals and early anatomically modern humans contributed to the current European gene pool.This study dovetails nicely with:Gutierrez G, Sanchez D, Marin A.
A reanalysis of the ancient mitochondrial DNA sequences recovered from Neandertal bones.
Mol Biol Evol. 2002 Aug;19(8):1359-66.Relethford JH.
Absence of regional affinities of Neandertal DNA with living humans does not reject multiregional evolution.
Am J Phys Anthropol. 2001 May;115(1):95-8.Krings M, Geisert H, Schmitz RW, Krainitzki H, Paabo S. DNA sequence of the mitochondrial hypervariable region II from the neandertal type specimen.Proc Natl Acad Sci U S A. 1999 May 11;96(10):5581-5.Templeton AR.
Out of Africa? What do genes tell us?
Curr Opin Genet Dev. 1997 Dec;7(6):841-7. Review.Krings M, Stone A, Schmitz RW, Krainitzki H, Stoneking M, Paabo S.
Neandertal DNA sequences and the origin of modern humans.
Cell. 1997 Jul 11;90(1):19-30.Ovchinnikov IV, Gotherstrom A, Romanova GP, Kharitonov VM, Liden K, Goodwin W.
Molecular analysis of Neanderthal DNA from the northern Caucasus.
Nature. 2000 Mar 30;404(6777):490-3.

Hi Peter,
Both the neanderthal studies and this latest study of fossil humans from the same time and location as other neanderthal finds does imply replacement and not interbreeding. Keep in mind that none of these studies include nuclear DNA analysis so all it says is that thus far, no neandertal or ancient human remains associated with them show evidence that neandertals and humans shared mtDNA haplotypes. What the researchers were attempting to test in the most recent paper was if Cro-Magnon had a human or neandertal like mtDNA sequence. Cro-magnon from this study apparantly falls right in the Joe Average range of human mtDNA diversity. All neandertals have been at the extreme outside edge (virtually no pairwise comparison overlap) with human mtDNA diversity.My problem with these types of studies is I feel they are a bit rigged from outset. If one found a neanderal specimen that gave a sequence like that of the Cro-magnon, it would likely be dismissed as a lab contamination. Thus, only neandertals that are very different are considered and thus they will of course then seem like there was no interbreeding. There are also statistical problems in that there are 3 neandertal sequences as opposed to the thousands of sampled human sequences. Another problem is from other studies it appears that in the relatively recent past (about 100-200Kya) humans underwent a nasty genetic bottleneck event..thus we have on average 4 times less genetic diversity than chimps, gorillas, or orangutans even though the human effective population size dwarfs all of those species and has for some time. This means, we may have lost a huge amount of mtDNA haplotypes that may have existed before the bottleneck i.e. we do not know what the actual mtDNA diversity was for the relevant period of time looking at modern mtDNA sequence distributions.Overall, the projects are neat to try but I would not personally draw any strong conclusions from them i.e. things like there was no interbreeding between neandertals and humans etc.cheers,
M

Mammuthus — you’re the extinction expert. Any speculations as to cause?But we didnt become extinct No idea what the cause may have been..on the other hand, human population density at the time must have been pretty low so it could have been a bad flu season, a generation of dumb hunters, bad weather and nothing for the gatherers to gather that knocked things down. We have also had some pretty nasty bottlenecks like the plague in Europe which may have made mutations in Cftr (the cystic fibrosis gene) more common than they would be otherwise. Another factor for Europe is that we did not walk into an uninhabited region..the neandertals were there (actually, looking at todays news in Germany..they also appear to be in office)...so given the current state of human affairs, open warfare could have been another cause for population decline..especially among hunter gatherers who would have diverted the calories needed for hunting and gathering to bonking each other on the head with big sticks...sounds like todays CNN headlines.

If they are only looking at mtDNA wouldn't that
only be able to establish that Neaderthal's never
had CroMagnon(-like) mothers?M: they would have to look at a lot of Cro-Magnon sequences (and neandertals) before that would be statistically meaningful..if dozens from all sorts of locations and times gave the same result it would be much more powerful evidence..as it stand it is interesting data but hardly conclusive.

Here is a review of human bottlenecks...as I remembered it, it was controversial...here is a paper reviewing the subject..abstract included.Annu Rev Genomics Hum Genet 2000;1:361-85 Related Articles, LinksGenetic perspectives on human origins and differentiation.Harpending H, Rogers A.Department of Anthropology, University of Utah, Salt Lake City, Utah 84112, USA.This is a review of genetic evidence about the ancient demography of the ancestors of our species and about the genesis of worldwide human diversity. The issue of whether or not a population size bottleneck occurred among our ancestors is under debate among geneticists as well as among anthropologists. The bottleneck, if it occurred, would confirm the Garden of Eden (GOE) model of the origin of modern humans. The competing model, multiregional evolution (MRE), posits that the number of human ancestors has been large, occupying much of the temperate Old World for the last two million years. While several classes of genetic marker seem to contain a strong signal of demographic recovery from a small number of ancestors, other nuclear loci show no such signal. The pattern at these loci is compatible with the existence of widespread balancing selection in humans. The study of human diversity at (putatively) neutral genetic marker loci has been hampered since the beginning by ascertainment bias since they were discovered in Europeans. The high levels of polymorphism at microsatellite loci means that they are free of this bias. Microsatellites exhibit a clear almost linear diversity gradient away from Africa, so that New World populations are approximately 15% less diverse than African populations. This pattern is not compatible with a model of a single large population expansion and colonization of most of the Earth by our ancestors but suggests, instead, gradual loss of diversity in successive colonization bottlenecks as our species grew and spread.and anotherMol Biol Evol 2001 Feb;18(2):214-22 Related Articles, LinksGlobal patterns of human DNA sequence variation in a 10-kb region on chromosome 1.Yu N, Zhao Z, Fu YX, Sambuughin N, Ramsay M, Jenkins T, Leskinen E, Patthy L, Jorde LB, Kuromori T, Li WH.Department of Ecology and Evolution, University of Chicago, 1101 East 57th Street, Chicago, IL 60637, USA.Human DNA variation is currently a subject of intense research because of its importance for studying human origins, evolution, and demographic history and for association studies of complex diseases. A approximately 10-kb region on chromosome 1, which contains only four small exons (each

Hmmm, Paleolithic warfare. Sounds like the bloody Europeans haven't changed much in 40,000 years. As far as neanderthalensis still living in Europe - have you seen pictures of Ken Ham? Talk about living proof that australopithecus still exists...M: Have not seen Ken Ham...but given some of the posts I have read on this site I wonder that certain not to be named individuals can walk on their knuckles and type at the same time

Since I have been out of the human pop gen literature for a while I had totally forgotten about the ascertainment bias issue. Since all the markers chosen were developed based on the European gene pool, they may give biased results in other populations since a "good" marker is usually determined based on a set of criteria based on the population being sampled. And it is a really critical issue as I am finding out as some markers I am using for mammoth genetics are really variable in elephants and then don't work worth a damn in mammoths. Some are really nice for African elephants but don't work in Asian elephants etc...all the markers were developed based on African elephant sequences.Anyway...the debate will go on for some time I think

Uhhh...thanks for the retina damage Quetzal...he looks like the Abraham Lincoln of the Australopithecines...

{I've taken the liberty to remove the content, which was yet another jab at Salty - Adminnemooseus}Now, people, how about the real topic?Adminnemooseus[This message has been edited by Adminnemooseus, 05-20-2003]

Okay Moose Okay ...I will attempt to refrain from salty jabsand swerving back on topic...did not get the entire article but the abstract sounds interesting..will try to order the paper.this is more along the lines of what Alan Tempelton has argued...it is also great to see someone trying to REDUCE the number of designated species rather than calling every new find a new speciesHomo 2003;53(3):201-24 Related Articles, LinksNumber of ancestral human species: a molecular perspective.Curnoe D, Thorne A.Department of Archaeology and Natural History, Research School of Pacific and Asian Studies, Australian National University, Canberra ACT 0200, Australia. d.curnoe@unsw.edu.auDespite the remarkable developments in molecular biology over the past three decades, anthropological genetics has had only limited impact on systematics in human evolution. Genetics offers the opportunity to objectively test taxonomies based on morphology and may be used to supplement conventional approaches to hominid systematics. Our analyses, examining chromosomes and 46 estimates of genetic distance, indicate there may have been only around 4 species on the direct line to modern humans and 5 species in total. This contrasts with current taxonomies recognising up to 23 species. The genetic proximity of humans and chimpanzees has been used to suggest these species are congeneric. Our analysis of genetic distances between them is consistent with this proposal. It is time that chimpanzees, living humans and all fossil humans be classified in Homo. The creation of new genera can no longer be a solution to the complexities of fossil morphologies. Published genetic distances between common chimpanzees and bonobos, along with evidence for interbreeding, suggest they should be assigned to a single species. The short distance between humans and chimpanzees also places a strict limit on the number of possible evolutionary 'side branches' that might be recognised on the human lineage. All fossil taxa were genetically very close to each other and likely to have been below congeneric genetic distances seen for many mammals. Our estimates of genetic divergence suggest that periods of around 2 million years are required to produce sufficient genetic distance to represent speciation. Therefore, Neanderthals and so-called H. erectus were genetically so close to contemporary H. sapiens they were unlikely to have been separate species. Thus, it is likely there was only one species of human (H. sapiens) for most of the last 2 million years. We estimate the divergence time of H. sapiens from 16 genetic distances to be around 1.7 Ma which is consistent with evidence for the earliest migration out of Africa. These findings call into question the mitochondrial "African Eve" hypothesis based on a far more recent origin for H. sapiens and show that humans did not go through a bottleneck in their recent evolutionary history. Given the large offset in evolutionary rates of molecules and morphology seen in human evolution, Homo species are likely to be characterised by high levels of morphological variation and low levels of genetic variability. Thus, molecular data suggest the limits for intraspecific morphological variation used by many palaeoanthropologists have been set too low. The role of phenotypic plasticity has been greatly underestimated in human evolution. We call into question the use of mtDNA for studies of human evolution. This DNA is under strong selection, which violates the assumption of selective neutrality. This issue should be addressed by geneticists, including a reassessment of its use for molecular clocks. There is a need for greater cooperation between palaeoanthropologists and anthropological geneticists to better understand human evolution and to bring palaeoanthropology into the mainstream of evolutionary biology.

Nobody listens to me either But more to the topic...todays New Scientist is reporting that a study by Morris Goodman's group (if you are out there SLPx maybe you can confirm this?) suggest that humans are about 99.4% similar to chimps in coding sequences. A recent study by Roy Britten suggested a 5% difference. The discrepancy between the two is that Goodman focused on coding sequences and Britten included non-coding.Thus Goodman calls for the inclusion of P. troglodytes and P. panicus in the genus Homo with us...Well, why not..I have met plenty of people who are hairier and less literate than a chimp and they are still Homo I saw an argument by a poster at internet infidels that I thought was also relevant...he argues it does not matter how you classify other primates..the creationists will turn it around and say ok, chimps descended from humans and represent the fall of man...

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Britten also includes the number of estimated sites in insertions and deletions. For example, the 'old way' would count a 100 base deletion as a single difference (since with rare exceptions, such deletions/insertions would have been one-time events). Britten's method would count a 100 base deletion as 100 differences.

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So, applying Britten's methoid universally would simply make everything more gentically distant from everything else, and thus not really impact the relative differences at all.

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I don't know how you feel about this but I think this would tend to greatly overestimate differences if every single base difference was counted as a discrete event.

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Interesting.. Creationists say the wackiest things. Like evolution has stopped, or humans were the 'target' of directed evolution...

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Or GUToB, non-random mutation, pop gen has nothing to do with evolution, semi-meiosis...the list could become rather substantial

Hi Scott,
It is a non-starter to a degree but it seems he is making it fashionableProc Natl Acad Sci U S A 2003 Apr 15;100(8):4661-5 Related Articles, LinksMajority of divergence between closely related DNA samples is due to indels.Britten RJ, Rowen L, Williams J, Cameron RA.California Institute of Technology, 101 Dahlia Avenue, Corona del Mar, CA 92625.It was recently shown that indels are responsible for more than twice as many unmatched nucleotides as are base substitutions between samples of chimpanzee and human DNA. A larger sample has now been examined and the result is similar. The number of indels is approximately 1/12th of the number of base substitutions and the average length of the indels is 36 nt, including indels up to 10 kb. The ratio (R(u)) of unpaired nucleotides attributable to indels to those attributable to substitutions is 3.0 for this 2 million-nt chimp DNA sample compared with human. There is similar evidence of a large value of R(u) for sea urchins from the polymorphism of a sample of Strongylocentrotus purpuratus DNA (R(u) = 3-4). Other work indicates that similarly, per nucleotide affected, large differences are seen for indels in the DNA polymorphism of the plant Arabidopsis thaliana (R(u) = 51). For the insect Drosophila melanogaster a high value of R(u) (4.5) has been determined. For the nematode Caenorhabditis elegans the polymorphism data are incomplete but high values of R(u) are likely. Comparison of two strains of Escherichia coli O157:H7 shows a preponderance of indels. Because these six examples are from very distant systematic groups the implication is that in general, for alignments of closely related DNA, indels are responsible for many more unmatched nucleotides than are base substitutions. Human genetic evidence suggests that indels are a major source of gene defects, indicating that indels are a significant source of evolutionary change.I don't per se object to examining non-coding DNA and considering indels, but to simply call every deleted or inserted base a discrete event is way to extreme. Your average provirus can be several kb long so if it is deleted by recombination and chimp has just a solo LTR and humans the entire virus it would be ridiculuos to call every base missing in the chimp a discrete deletion event....oh well, someone will write a paper again revising the numbers down the road.

Hi Andya,
Here is a link to the journal Homo containing this article. In long form the journal is the Journal of Comparative Human Biology. It seems you need a subscription to read the articles (which I don't have) but my guess is you can purchase individual articles.cheers,
MElsevier | Ein Unternehmen fr Informationsanalysen | Empowering Knowledge

Ha! Even the guys doing this work admit that it is not very scientificNature 423, 468 (2003); doi:10.1038/423468b
Anthropologists cast doubt on human DNA evidencefrom the article

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But experts question whether Bertorelle, and others who are attempting similar experiments, can rule out contamination with material from modern humans. "Cro-Magnon DNA is so similar to modern human DNA that there is no way to say whether what has been seen is real," says Svante Pbo, a director at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

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and

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But such controls cannot definitively rule out contamination of the Cro-Magnon sample. Researchers such as Pbo and Cooper see no way to resolve the issue, and are now increasingly questioning the value of studies such as Bertorelle's. "We know that contamination is almost impossible to avoid," laments Cooper.

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What Cooper and Pbo fail to acknowledge is that they (and everyone else) should then question whether their own neandertal work (and that of other groups) is even really science. If you only believe fossil human sequences which look different from modern human sequences are bona fide endogenous DNA and call all modern-like human sequences from fossils suspect contamination..what can you really conclude from this type of work at all? The neandertal crowd were claiming that the differences found in the 3 neandertals sequenced to date indicate that neandertals were not Homo sapiens and did not interbreed. From 3 samples they claim that humans replaced neandertals and the neandertal lineage became extinct. However, according to Paabo and Cooper, if a neandertal is ever extracted that turns out to be very similar to human mtDNA sequences, they will claim it is contamination and unreliable. So, they a priori determine that neandertals were different from modern humans because they only accept different sequences as real...what's the point of doing the experiments in the first place if you pre-determine the answer you will accept?cheers,
M