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.

Is that saying that the mtDNA studies support
demographic replacement?Neaderthal and CroMagnon were gentically closer 23-25 thou years
ago than they were more recently?

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

Here's a recent paper that discusses the bottleneck:Gabor Marth, et al, 2003, Sequence variations in the public human genome data reflect a bottlenecked population history", PNAS 100:376-381

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Single-nucleotide polymorphisms (SNPs) constitute the great majority of variations in the human genome, and as heritable variable landmarks they are useful markers for disease mapping and resolving population structure. Redundant coverage in overlaps of large-insert genomic clones, sequenced as part of the Human Genome Project, comprises a quarter of the genome, and it is representative in terms of base compositional and functional sequence features. We mined these regions to produce 500,000 high-confidence SNP candidates as a uniform resource for describing nucleotide diversity and its regional variation within the genome. Distributions of marker density observed at different overlap length scales under a model of recombination and population size change show that the history of the population represented by the public genome sequence is one of collapse followed by a recent phase of mild size recovery. The inferred times of collapse and recovery are Upper Paleolithic, in agreement with archaeological evidence of the initial modern human colonization of Europe.

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This paper puts the 4-7 fold population decline at around 40,000 years ago. Three different tests of the data showed strong evidence of severe linkage disequilibrium in Homo sapiens, at least in Europe.Mammuthus — you’re the extinction expert. Any speculations as to cause?

If they are only looking at mtDNA wouldn't that
only be able to establish that Neaderthal's never
had CroMagnon(-like) mothers?Surely it wouldn't preclude Neaderthal and Cro-Magnon
interbreeding in any case (especially with relatively
few Neaderthal sequences).... which I guess leads me to agree that the studies
aren't even remotely conclusive in that regard

Could the same data mean that there was a small
population at about that time, or is there other
data that suggests that before that time the
pop. was larger?

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.

Hey Peter,They don't really refer to population size, per se, rather population genetic variability. Given known substitution rates, they simply didn't discover nearly enough polymorphisms. What the data DID show - again based on known substitution rates - was that the apparent homogenization in Europeans (because they were using European samples) is consistent with a bottleneck traced back to around 40 kya. As Mammuthus pointed out, there could be a lot of problems with the analysis and a lot of other factors, so there's not a "smoking gun" necessarily. It might be indicative, however, if other evidence is discovered. The article concludes with fairly high confidence on the part of the authors.

Yeah, but it sounds like if the authors were right, the Europeans came pretty close. Might be that the only thing preventing it was the fact that they WERE small-scale hunter-gatherers. IOW, lots of local population extinctions homogenizing the gene pool followed by slow recovery. Just like cheetahs and elephant seals...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...

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

Thanks for the links. I'd read the first article before. I'd like to point out that the reference I cited was from this past January, so might be either a more definitive study OR simply the next shot across the bows in the GoE/OoA war.

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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.

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My reference didn't dispute this - and in fact discussed the problems with previous studies in much the same fashion. All they tried to show was that there WAS evidence, based on SNPs, that there may have been a bottleneck in European populations - the population from which came the samples. They made no conclusions about whether this represented ALL human populations, or simply the geographical population based in Europe. So, IMO, they weren't trying to get in on the other debate. I'm relatively impressed with the way they handled and presented the data - since it was based on sequences derived from the Human Genome Project, they weren't actually in the lab. And they made a pretty good case for the way they chose and manipulated the data. Not conclusive, of course, but pretty indicative.

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We suggest that both the "Out of Africa" and the multiregional models are too simple to explain the evolution of modern humans.

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This is probably a pretty valid conclusion. After all, various populations - even widely distributed across continental Europe, for instance - could easily have suffered a genetic bottleneck without effecting other regional populations in the slightest.And the debate goes on...[This message has been edited by Quetzal, 05-20-2003]

Ah, you don't know what you've been missing. Presented for your edification: Ken Ham, founder, president, and CEO of Answers in Genesis (and living proof that Australopithecus robustus still lives - or alternatively, the close relationship between Pan and Homo):

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