Ancient Human DNA - A cautionary statement

[Jacques Cinq-Mars]

All,

Despite the fact that it is based on a very recent set of data (palaeoanthropologically speaking), the following release is worth reading by all people interested in waxing eloquent about matters of "molecular genealogy" - especially when these are regurgitated by the media or, to be fair, by authors/researchers who want to sell books.

Jacques Cinq-Mars

Ancient skeletons can trick researchers
For further information, please contact:
Barbara Hott
University of Oxford
barbara.hott@admin.ox.ac.uk
01865 280531

13 February 2003

keywords
Archaeology, Life Sciences
 
  The genetic information obtained from ancient human skeletons may often give very misleading results, according to latest research at Oxford University?s Henry Wellcome Ancient Biomolecules Centre. Damage to the ancient DNA can confuse studies of geographic origin and relatedness.

The researchers came across oddities during a study of Viking specimens for the BBC 'Blood of the Vikings' series, when around 50 per cent of the specimens they analysed appeared to be genetically middle Eastern. Further research revealed that many of the DNA sequences were damaged at a key base that separates European sequences form Middle Eastern genetic types, a damage which made the skeletons appear to have originated in the Levant.

After studying DNA damage more closely, research student Tom Gilbert found that such damage events are concentrated in 'hotspots', which means that a high proportion of DNA molecules can be modified at the same point. These hotspots appear to be in positions that also differ between different human groups, in other words, DNA damage affects the same genetic positions as evolutionary change.

Professor Alan Cooper, Director of the Henry Wellcome Ancient Biomolecules Centre at the University of Oxford, said: 'As few other ancient human studies have investigated the DNA damage to any degree (with the exception of the Neandertal and Ice Man studies), it is likely that many results seen on TV archaeological programmes are erroneous. On the other hand, now that this phenomenon has been recognised, it is possible to survey the ancient sequences for damage more accurately, and determine the correct original genetic type ? opening the way for more reliable future studies.

'It also appears that we can use damage caused after death to examine how DNA damage occurs during life ? a completely unanticipated, and somewhat ironic result. Potentially this allows us to get uniquely separate views of the two major evolutionary processes, mutation and selection.'

Further information can be found here.

[Jacques Cinq-Mars]

I noticed that the URL access provided in my earlier post, may require "registration". So, if you have a problem with this, here is the rest of the information:

Jacques Cinq-Mars

Notes for editor

The findings have been validated by researchers at the University of Copenhagen who independently replicated the results.

Other recent research by the Ancient Biomolecules Centre included findings regarding the origin of the Andaman islanders which led to conclusions about early human migration, see http://www.admin.ox.ac.uk/po/030128.shtml

The Henry Wellcome Ancient Biomolecules Centre, directed by Professor Alan Cooper, is part of the Oxford University Department of Zoology. Current research areas include the analysis of specimens in the Beringian permafrost, climate change, human impact, evolution and archaeological specimens. Following a successful bid to the Wellcome Trust and the UK government (JIF grant), a dedicated new building is currently about to open in the Science Area, which will serve as the centre for Ancient DNA research in the UK. For further information see http://abc.zoo.ox.ac.uk.

Peer reviewed publication and references
Gilbert, M Thomas P et al, 2003, 'Distribution Patterns of Postmortem Damage in Human Mitochondrial DNA', American Journal of Human Genetics 72: 32–47, and Gilbert, M Thomas P et al, 2003, 'Characterization of Genetic Miscoding Lesions Caused by Postmortem Damage', American Journal of Human Genetics 72: 48–61.

Reference URL : http://abc.zoo.ox.ac.uk

 

[Dale Hoogeveen]

All,

Despite the fact that it is based on a very recent set of data (palaeoanthropologically speaking), the following release is worth reading by all people interested in waxing eloquent about matters of "molecular genealogy" - especially when these are regurgitated by the media or, to be fair, by authors/researchers who want to sell books.

Jacques Cinq-Mars

Ancient skeletons can trick researchers
For further information, please contact:
Barbara Hott
University of Oxford
barbara.hott@admin.ox.ac.uk
01865 280531

13 February 2003

keywords
Archaeology, Life Sciences

 The genetic information obtained from ancient human skeletons may often give very misleading results, according to latest research at Oxford University?s Henry Wellcome Ancient Biomolecules Centre. Damage to the ancient DNA can confuse studies of geographic origin and relatedness.

The researchers came across oddities during a study of Viking specimens for the BBC 'Blood of the Vikings' series, when around 50 per cent of the specimens they analysed appeared to be genetically middle Eastern. Further research revealed that many of the DNA sequences were damaged at a key base that separates European sequences form Middle Eastern genetic types, a damage which made the skeletons appear to have originated in the Levant.

After studying DNA damage more closely, research student Tom Gilbert found that such damage events are concentrated in 'hotspots', which means that a high proportion of DNA molecules can be modified at the same point. These hotspots appear to be in positions that also differ between different human groups, in other words, DNA damage affects the same genetic positions as evolutionary change.

Professor Alan Cooper, Director of the Henry Wellcome Ancient Biomolecules Centre at the University of Oxford, said: 'As few other ancient human studies have investigated the DNA damage to any degree (with the exception of the Neandertal and Ice Man studies), it is likely that many results seen on TV archaeological programmes are erroneous. On the other hand, now that this phenomenon has been recognised, it is possible to survey the ancient sequences for damage more accurately, and determine the correct original genetic type ? opening the way for more reliable future studies.

'It also appears that we can use damage caused after death to examine how DNA damage occurs during life ? a completely unanticipated, and somewhat ironic result. Potentially this allows us to get uniquely separate views of the two major evolutionary processes, mutation and selection.'

Further information can be found here.

Hi Jacques,

The above is not the only reservation stated about possible misinterpretation of postmortum changes to ancient DNA.  Neanderthal mtDNA sequences also have been criticized.  I find it interesting that a very small difference in likelihood seperates inclussion or exclusion of Neanderthals mtDNA in modern sets (guitierrez, et al - below), as well as potential "lesion" misinterpretation in Neanderthals (Caldararo and Grabow - also below) appearing to correlate to potential "hot-spot" misinterpretation in the much more recent Viking studies mentioned above.

Ancient DNA and Human origins:  The role of gene sequence variation in the species concept.  
by Niccolo Caldararo
http://human-nature.com/nibbs/02/caldararo.pdf

A Reanalysis of the Ancient Mitochondrial DNA Sequences Recovered from Neanderthal Bones
by Gabriel Guitierrez, Diego Sanchez, and Antonio Marin
http://www.rdos.net/copies/Neanderthal-mtDNA.pdf

The above two papers are available for direct download.

also:
N. Caldararo & S. Gabow, "Mitochondrial DNA analysis and the place of Neanderthals in Homo", Ancient Biomolecules, 3, 135-158, (2000)
    Ancient Biomolecules
http://www.tandf.co.uk/journals/titles/13586122.html

Unfortunately Ancient Biomolecules is not free.

Dutch

[Jacques Cinq-Mars]

All,

Despite the fact that it is based on a very recent set of data (palaeoanthropologically speaking), the following release is worth reading by all people interested in waxing eloquent about matters of "molecular genealogy" - especially when these are regurgitated by the media or, to be fair, by authors/researchers who want to sell books.
<snip>

Hi Jacques,

The above is not the only reservation stated about possible misinterpretation of postmortum changes to ancient DNA.  Neanderthal mtDNA sequences also have been criticized.  I find it interesting that a very small difference in likelihood seperates inclussion or exclusion of Neanderthals mtDNA in modern sets (guitierrez, et al - below), as well as potential "lesion" misinterpretation in Neanderthals (Caldararo and Grabow - also below) appearing to correlate to potential "hot-spot" misinterpretation in the much more recent Viking studies mentioned above.

Ancient DNA and Human origins:  The role of gene sequence variation in the species concept.  
by Niccolo Caldararo
http://human-nature.com/nibbs/02/caldararo.pdf

A Reanalysis of the Ancient Mitochondrial DNA Sequences Recovered from Neanderthal Bones
by Gabriel Guitierrez, Diego Sanchez, and Antonio arin
http://www.rdos.net/copies/Neanderthal-mtDNA.pdf

The above two papers are available for direct download.

also:
N. Caldararo & S. Gabow, "Mitochondrial DNA analysis and the place of Neanderthals in Homo", Ancient Biomolecules, 3, 135-158, (2000)
    Ancient Biomolecules
http://www.tandf.co.uk/journals/titles/13586122.html

Unfortunately Ancient Biomolecules is not free.

Dutch

If I recall, Niccolo Caldararo was kind enough to provide the participants to the old Palanth-l with a copy of his Ancient Biomolecules paper. It is somewhere in my files!. I'll see if I can retrieve it and pass it on.

Jacques

[lagarvelho]

Jacques and all:

I've read the two free-for-download papers, and whatever anyone's ultimate conclusions about this matter, they are well worth reading.  I'd like to see the Caldararo paper from Biomolecules, though.  Hope you can find it in your files.
Anne G

[Jacques Cinq-Mars]

I suppose I am once again breaking rules, here, with this shameless example of cross posting (from Anthro-L), but here is another recent, mtDNA "cautionary" signal that I had somehow missed. It will be interesting to see how this all unfolds, especially for palaeoanthropological studies.

Jacques Cinq-Mars

Those interested in traceing MtDNA Eve should be interested in an article published in the February 20, 2003 issue of 'Nature' pages 773 and 774.
____________________________
Error Reports Threaten To Unravel Databases Of Mitochondrial DNA

by Carina Dennis

More than half of all published studies of human mitochondrisl DNA (mtDNA) sequences contain mistakes, according to a geneticist at the University of Cambridge.

To the occasional chagrin of his peers, Peter Forster has repeatedly pointed out errors in published mtDNA sequences, the genetic material from cells mitochondria, which are inherited from the mother.  But his commmentary in the latest issue of 'Annals of Human Genetics' argues that the problem is far bigger than researchers had imagined.

The mistakes may be so extensive that geneticists could be drawing incorrect conclusions in studies of human populations and evolution, says Forster.  They may also confuse forensic analyses that rely on the published squences, he adds.

(cut)

Published mtDNA sequences are popular tools for investigating the evolution and demography of human populations.  Forster has been compiling a database of corrected mitochondrial sequences published since 1981, when the complete sequence of human mtDNA - known as the 'Cambridge reference sequence' - was published.  His coleagues' responses when he informs them of errors are varied. "Antagonism would be an understatement in some cases," he says.

(cut)

Perhaps the gravest concern surrounds forensic investigations.  Because large numbers of mitochondria are present in cells, they are often used to identify degraded samples from which nuclear DNA cannot be obtained.  But the region of mtDNA typicaly used in forensics - the 'control region' - is highly variable, says geneticist Douglas Wallace of the University of Californis, Irvine.  "People don't appreciate the fact that the control region can undergo different mutations in different cells," he says.  For instance, there might be differences between mtDNA from someone's blood and from the same person's hair follicle.

(cut)

Forster notes that nuclear DNA sequences in public databases are also plagued by errors, and that this may be an even greater problem, as such mistakes are more difficult to detect.

[Dale Hoogeveen]

I suppose I am once again breaking rules, here, with this shameless example of cross posting (from Anthro-L), but here is another recent, mtDNA "cautionary" signal that I had somehow missed. It will be interesting to see how this all unfolds, especially for palaeoanthropological studies.

Jacques Cinq-Mars

Hi Jacques,

There have been a number of cautionary signals in regard to mtDNA inheritance all along.  Mistakes in sequencing  both technically and in assumptive relationships keep getting pointed out.  (And need to be!)  As close as the probabilities for determining the most likely sets of calculations actually are, any one of those signals can produce a complete reorganization of parsimony.

Let me add a couple or three (or so) additional considerations:

First mtDNA is transmitted between generations as a colony rather than a single instance of a genotype as is the case for the chromosomal component of a gamete.  That would require population dynamics as a basis rather than mathematical recombination of single (and therefore uniform) genetic sets.  mtDNA sampling is testing of a colony rather than direct measurement of a specific geneotype.

Second mtDNA is almost completely transmitted between generations as a rider colony in the primary oocyte which has a very tiny active period during any mammalian female generation.  The developing human female gamete spends approximately 99% of the female generation dormant, and is therefore very nearly a beginning of generation process rather than an end of generation process as is the case for spermatogenesis.  

The latter produces a virtual constant value for female gamete active history regardless of age of mother at conception, which badly screws up application of female generational turnover, requiring a double clocking model with one application to active period and another with both different rate and length of time for the dormancy period.  To me that so confuses overtime application of inheritance patterns that comparing parsimonies based on a single universal clocking becomes pointless.

Finally mtDNA is well known to be much more highly mutable than chromosomal genetics and therefore is inherantly clocked at different rates which when added to beginning of generation female meiosis scheduling makes adjustments between chromosomal inheritance and mtDNA inheritance very complicated and probably species-specific as well, since meiosis scheduling in fetal female development and oocyte dormancy periods certainly are species-specific characters.

mtDNA is not suited to any simple set of calculations for long term inheritance studies, certainly not for periods involving the lifetime of species or translation to chromosomal inheritance patterns.  Any such that include multiple species without very complex adjustment factors between them are certain to be mistaken.

It is important to also remember that not only are mtDNA lineages that lead to paternal mtDNA expression discarded, mother-child transmission also means that very nearly all maternal ancestral lineages are also.  So maternal type does not even represent her maternal ancestry, only the single unbroken mother-daughter line that leads to her (and, of course, at least one of those has to be maintained to prevent species extinction and there may very well be species-specific quantiites of those mother-daughter lineages necessary to maintain particular types), and then her active adult mtDNA expression has something like 100 times the added genetic history in her lifetime alone (depending on her age at the conception of her child) over what she is carrying in the developing gamete that will be that child.  So active mtDNA expression in adult humans is actually generations different from reproductively transmitted colonies simply in a single female generation despite the fact that both start from the same set at fertilization.

Statistically no offspring can represent the accumulations of mtDNA lineage extinctions that lead up to it, not only individually but also by extention and therefore not in mass either.  Lack of evidence can certainly not in this case be evidence of lack, which is exactly what African Eve calculations are based on.
 
I think that African Eve is the genetics version of Piltdown man, although I do not think in this case it was intentionally perpetrated. The over-simplification of the material has been simply too elegant to resist.  Hopefully that will not discredit the actual technology that has been developed and is developing for gene sequencing which is one of the most important developments, IMO, in the study of genetics, ranking with Mendel's peas and the double helix model for DNA.

Dutch

[lagarvelho]

Dale:

The "African Eve" may be the molecular version of the Piltdown Man, but if true, unlike Piltdown, it's going to be much harder to refut in anything like the way that Piltdown was.  There will be "believers" for years to come.  Witness the recent outpourings from Richard Klein.
Anne G

[Dale Hoogeveen]

Dale:

The "African Eve" may be the molecular version of the Piltdown Man, but if true, unlike Piltdown, it's going to be much harder to refut in anything like the way that Piltdown was.  There will be "believers" for years to come.  Witness the recent outpourings from Richard Klein.
Anne G

Hi Anne,

Unfortuneately Piltdown lasted a very long time.

mtDNA has some very important things to tell us, it's just that chronology is definitely not one of its long suits.

It is interesting that Klein speculates that Neanderthals were isolated clumps of population, but the hard evidence for population isolation is still in Africa and it comes from mtDNA lineages studies.  They show distinct, long term localized populations at least in regard to human female breeding groups, while the rest of the world shows much more generalized integration.  I suppose that I object most to lumping Africans into one overwhelming wave, when mtDNA lineages actually shows continuing isolation between African female populations.

I suspect that when viewed from the angle of human concealed ovulation and what I guess can be considered incomplete or at least socially manageable estrus, mtDNA in humans may tend toward minimal mtDNA lineage maintenance per female breeding population as a natural part of our reproductive strategy.  IOW distinct lineages show isolation while integrated populations show a decline in the number of maintained lineages despite increases in actual numbers (including effective breeders) - essentially the same number of necessarily maintained mtDNA lineages per breeding group independant of the size of that group.  As groups integrate the minimum number of mtDNA lineages supported by the total human species declines. If we as a species tend toward minimum mtDNA lineages, diversity also declines as integration proceeds.

All in all mtDNA tells me that population isolation factors are different and more intense in Africa than in the rest of the world.  That has all kinds of reprocussions beyond whether some mitochondrial Eve or Eve group existed in Africa some 150,000 years ago or so.  That is really quite minor;  it will stand or fall on its own, but it screens more important issues, such as differential movement perhaps on the basis of gender and how that might affect ancient hunter-gatherer models, many of which are developed at least partly from existing African examples.  Or perhaps how mtDNA lineage maintenance may vary from species to species based on reproductive strategy.  You should be aware that wild canids also show restricted mtDNA variation. (There have even been a number of arguments to the effect that "isolated" mtDNA lineages  indicates a number of Canis lupis species.)  There is important lack of adult female participation in canid reproduction which may have a parrallel effect to the large number of non- or under-reproductive human females (in a very real sense that would apply to any pre-menopausal woman who is not either nursing or pregnant)  when it comes to inherant levels of mtDNA lineage diversity.  I suspect that there is also a parrallel affect on Y chromosome diveristy based on proportions of male reproductive participation, even though the genetic material is somewhat different and is scheduled differently during meiosis.

(FWIW Y chromosome studies seem to indicate that there are huge proportions of the human male population that are non- or under-reproductive as well, which should also show restricted human Y chromosome diversity and I think that is also the case.  If both human sexes are underreproductive perhaps there is a common cause, such as... incomplete human maturation?)

There are piles of interesting stuff about mtDNA (and human reproduction in general...  Of course there are!).  To me African Eve is a snakeoil stand, that just happens to be in front of the gate to the rest of the carnival.

Dutch