2. Neanderthal deciphered ? (en)

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Version francaise

a. Brain development in modern humans and chimpanzees

All started with a conference by JJ Hublin. The conference was entitled “Neanderthal deciphered” when studies had just shown the opposite. In fact, it seems to have as a hidden goal to restore the ape image of the Neanderthal. This is apparently what they decided to do, and indeed, as could be expected. We are witnessing the creation of a fable, with the evolution and Out of Africa as key words, in all cases, regardless of whether the rest of the proof is gone.

Thus, at 0:27:30 we learn for example that Neanderthal from Mezmaiskaya (Russia), was closer to Denisova than the other Neanderthals. Of course, it is concluded that they originate from the same strain. In fact, as explained in the articles listed below, it is hybridized to Denisova and the Neanderthal women from Vindija (Croatia) are likely hybridized (but less) too. This distorts of course their calculations (That is therefore some people claimed that Asians had the greater Neanderthal DNS part), but nobody puts anything in question. Concerning that, I invite you to look at these articles:
3. Genetic
4. Secrets of the neanderthal genome
5. The swept away genes

The conference is visible here:
http://fora.tv/2011/01/18/Dr_Jean-Jacques_Hublin_Neanderthals_Deciphered

Gaps in their logic does not scare … Other extracts are really specials, as the genetic diversity of chimpanzees at 0:21, which is a contradiction with the claims of those who say that chimpanzees have 99% DNA in common with humans. But again, these issues have already been discussed before.

http://news.sciencemag.org/sciencenow/2010/11/neandertal-brains-developed-more.html

“With brains as big as ours, Neandertals were no dumb brutes. But their brains may have developed in a manner much different from the way ours do, according to a new study.”

No, Neanderthal brain was not as large as ours, but larger, and this is a big difference because then the differences in shape are not as significant.
A bit like in the time of the Church and Marcellin Boule, there is a destruction of the status of the poor Neanderthal who, unfortunately, is very unloved and especially very disturbing. But anyway, here it is, among other things, there they have linked the case with autism. Thus we hear JJ Hublin in English with a French accent, saying this at 0:37:45 :

“It has been possible again using this method of geometric morphometric to assess the changes in shape of the brain from the birth to the adulthood in Neanderthals and in modern humans. This chart is a bit busy, but I will try to simplify it. This green line that you have here is the morphological trajectory of a chimpanzee between its birth and adulthood and… to make it very simple it follows this curve trajectory so there is a change in size but there is also a change in shape.”

Neanderthal deciphered brain development Hublin conference

Neanderthal deciphered – Brain development

In blue : Modern human
In red : Neanderthal
In green : Chimpanzee

“When you look at modern humans, you also have this kind of curve a bit similar to the one of the chimpanzees and approximately paralell but not between birth and adulthood but between one year old and adulthood.

The difference between the chimpanzees and the modern human is that modern human, they added this stade of development that does not existing in chimpanzees and this is a vertical portion of the trajectory here. This vertical segment is what is going on between birth and one year old and what is going on along this segment is the development of this parietal areas and this changes in the cerebelum area, which means that the differences that we have between a neanderthal adult and a modern adult is something that develop in the very beggining of life and this is very important because we know that what is going on in the brain in the very first month and years of life is crucial. Why ? Because humans they develop their brain in interaction with the environment. The brain of humans is a very peculiar organ, when we get born, we have a brain which is about a quarter of the adult size and three quarter of the size of our brain develop after birth and mostly between birth and four years old, ok ?

And during this period of time where the size of the brain is multiply by 4 we interact with our mother, with our friends, our brothers, with the dog, with city environment and so, the brain of humans is a computer which is rewritten what it is used. And it is likely why we are able to master something like language for example, so it is very crucial to identify differnces between Neanderthals and modern humans not just in general in the shape of the brain but also in this time scale and to figurate that this differences are etablished very early. It looks like modern humans have a longer development of their brain and it is likely that it has some influence on the complexity of our cognitive abilities, so all this color here is Neanderthals that are been plotted … and what you see is that also at birth the brain of a Neanderthal is very close from the shape of the brain of a modern baby. The trajectory leeding to an adult shape is parallell to the one we have in chimpanzees and that not show this long vertical segment here that we have in modern humans.

And this is something very new, you see, it has been published this year so just a few months ago actually and it’s an observation that is interesting to put together with something that our collegues geneticist have found, this is a list of a number of genes that are different between Neanderthals and moderns humans and when you look at this list of genes, there are at least to or three genes here which are related to the brain development and the development of cognitive abilities and in particular there are to genes here which are implicated in autism in modern children and this is very interesting because people working on autism and how autism develops argue that one of the mechanism of development of autism is related to the speed of development of the brain so in other words autistic childreen seems to have a brain that develop faster than the brain of other kids.

So it is remarkable to find the same kinds of differences with Neanderthals and modern humans. I am not arguing that Neanderthal was autistic but what I am saying is that genes which are involved in the development of the brain in humans today are different between Neanderthals and modern humans and when we look at the shape trajectory of the brain during the first year of life we also see differences between Neanderthals and modern humans and I believe it is very likely implication in term of cognitive abilities and the complexity of this cognitive abilities in modern humans and Neanderthals.”

The genes listed are a small group of genes selected from a quite big group that I mentioned here. The genes called « the swept away genes ». He says therefore that the swept away genes, that is to say, the genes that are most different in Neanderthals, compared to the tested modern individuals, contain the genes listed below (this list is, again, a very small part of this group of « swept away genes »):

Neanderthal deciphered conference Hublin - The swept away genes

The swept away genes

b. Autism: The Genes involved vary from one family to another

Indeed, the list contains CADPS2 and AUTS2, genes involved in autism, but it is presented as if they were more or less the genes for autism, without specifying that autism itself is not linked to any specific gene, and not even to a group of genes. Autism in the same family, seems to be linked to the same group of genes, but only in the same family. Thus, CADPS2 and AUTS2 are involved in autism, but to bind autism, as well as some identified genetic diseases, to one or two apparently different genes in Neanderthal, is in my opinion a mistake. Of course, we can think that this difference is not so important, yet it changes a lot…

Indeed, there are many publications that claim to have found a gene involved in 1% of cases of autism, or a group of genes found in two families with disorders of the autism spectrum… There are many attempts to find the gene or genes involved in autism, or understand its mechanism. The Autism Genome Project has highlighted some features that occur frequently in the tested families, but they also found that the so-called “autism genes” seems to be the same in the same family, but not from one family to another. The reasons are clearly genetic, but unconventional.

On this site you can access all the genes hypothetically involved in autism:
http://autism.mindspec.org

About CADPS2 : http://autism.mindspec.org/GeneDetail/CADPS2

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1821065/pdf/JCI0729031.pdf

Figure 10 autism

Figure 10

And about AUTS2 that is certainly associated with some cases of autism, but also with other mental problems, and mental retardation (we must remember that this should not be confused with autism stricto sensus).

http://autism.mindspec.org/GeneDetail/AUTS2
Multiple studies have identified rare mutations in the AUTS2 gene with autism. In addition, several studies have found that rare variants in AUTS2 are identified with mental retardation, ADHD, epilepsy and genetically associated with alchohol consumption.

The fact that the AUTS2 gene is different in Neanderthal, does not mean that Neanderthal had the version of the gene which was associated with these diseases, but on the contrary, it is likely that hybridization has created a failure in the gene.

http://www.ncbi.nlm.nih.gov/pubmed/17211639?dopt=Abstract :

Mutations in autism susceptibility candidate 2 (AUTS2) in patients with mental retardation.
We report on three unrelated mentally disabled patients, each carrying a de novo balanced translocation that truncates the autism susceptibility candidate 2 (AUTS2) gene at 7q11.2. One of our patients shows relatively mild mental retardation; the other two display more profound disorders. One patient is also physically disabled, exhibiting urogenital and limb malformations in addition to severe mental retardation. The function of AUTS2 is presently unknown, but it has been shown to be disrupted in monozygotic twins with autism and mental retardation, both carrying a translocation t(7;20)(q11.2;p11.2) (de la Barra et al. in Rev Chil Pediatr 57:549-554, 1986; Sultana et al. in Genomics 80:129-134, 2002). Given the overlap of this autism/mental retardation (MR) phenotype and the MR-associated disorders in our patients, together with the fact that mapping of the additional autosomal breakpoints involved did not disclose obvious candidate disease genes, we ascertain with this study that AUTS2 mutations are clearly linked to autosomal dominant mental retardation.

www.inserm.fr/content/download/…/cp_betancurl_22_02_2007.pdf

Catalina Betancur, chercheur à l’unité Inserm U513 à Créteil et un des investigateurs principaux de l’étude (Autism Genome Project), déclare : « Les résultats de cette étude soulignent que l’autisme n’est pas une maladie avec une cause unique, mais un trouble comportemental avec de nombreuses causes génétiques et dont les gènes impliqués varient d’une famille à l’autre ».

Catalina Betancur, a researcher at Inserm U513 in Créteil and one of the principal investigators of the study (Autism Genome Project), said: “The results of this study highlight that autism is not a disease with a single cause but a behavioral disorder with many genetic causes and whose genes vary from one family to another.

c. Brain development in Neanderthal child

Mr. Hublin continues, ensuring that the development of the Neanderthal child brain follows the same pattern as that of chimpanzees, and that it is also the same in autism. I think this is totally wrong.
He explains that it probably develops faster in Neanderthal, and in autism, and I think this deserves to be detailed.

He explains that these developments (Neanderthals and modern) have two different developments to bring a large brain, indicating that modern humans, as Neanderthals, has a big brain. Two large brains, he says, still omitting to specify their size difference. Neanderthals (but also the first Cro-Magnons, the hybrids) had a larger brain than the so-called modern human. Evolution takes a hit, but…

The fact that Mr. Hublin draws such conclusions about the brain development of young Neanderthals is quite disturbing. Neanderthal indeed, compared to other fossil species, has delivered a certain number (but still very limited) of skeletons of children, even newborns.

But to guess the speed of brain development, it seems that science believes it is omnipotent. It is never expressed the idea that working on the remains of a newborn like that of Moustier 2, is not necessarily objective, and can give completely false results. A newborn does not die of a hunting accident, then why is he dead? Was it premature? Does he have a malformation?
But, assuming that the data are perfectly right, I would conclude as follow:

A larger brain

Mr. Hublin quotes Gunz et al., That is to say, he quotes himself.
http://homepages.rpi.edu/ calhop ~ / Creedence_tapes / neanderthal.pdf

Mr. Hublin wrote that the cranial capacity of the Neanderthal Le Moustier 2 is estimated, still based on its own studies, to 408-428 cm3 with an average of 418 cm3, which he says is similar to modern humans. (Mezmaiskaya 1, the other Neanderthal newborn that is found have a cranial capacity which is estimated to 422 to 436 cm3 with an average of 429 cm3: The reconstructed endocranial volumes for the Mezmaiskaya specimen range between 422–436 cc cf. 21 in http://paleo.revues.org/2107#tocto1n4)

The cranial capacity of a newborn is about ¼ of the cranial capacity of the adult, as Mr. Hublin explains himself, and modern human with an average cranial capacity of 1400 cm3 in adulthood, might have a newborn cranial capacity of about 350 cm3 for the newborn, that is to say a big difference (73.5 cm3 on average) for a so small skull. We can therefore safely say that the cranial capacity of Neanderthals and modern newborns are not “similar”, but that they show the same difference between the skulls of the two species as in adulthood. 423.5 X4 = 1694cm3

(A) For the virtual reconstruction of the Neanderthal neonate Le Moustier 2, CT scans of individual fragments were assembled on the computer. Fragments that were mirror-imaged to the other side are plotted in a darker shade. The gray surface represents estimated missing data. At birth, Neanderthals and modern humans have very similar endocranial volumes and shapes (red: Le Moustier 2; blue: modern human).

Modern and neanderthal babies skull

Modern and neanderthal babies skull

Indeed, from the front, both newborns skulls have similar shapes, but the profile shows that the red skull Le Moustier 2 is much longer back, and it is much bigger.

Indeed, from the front, both newborns skulls of similar shapes, but the profile we can see that the red skull Moustier largely continues farther back, and it is much bigger.

Finally, the graph that M.Hublin presents to us has no scale, no measure, and even age groups, which must be guessed, are only indicated for the modern human. Thus, we find the Moustier 1 (15) below the group 6 (adults) modern human, and Neanderthals adults far ahead. Indeed, at first glance, we may believe M.Hublin when he says that the shape of the Neanderthal brain growth is the same as that of the chimpanzee, except that it presents two or three drawings without any actual data on Neanderthal:

Brain development modern and neanderthal

Brain development modern and neanderthal

http://homepages.rpi.edu/~calhop/Creedence_tapes/neanderthal.pdf

Here is another graph from the following study (1994):
http://193.146.160.29/gtb/sod/usu/$UBUG/repositorio/10311405_Coqueugniot.pdf

Table2 Graph5 fossil children

Table2 Graph5

(NB ! All the fossil skulls studied and reported here are not Neanderthals, I highlighted the Neanderthals in brown, and I colored in yellow the variability area for cranial capacity among modern children, to facilitate a quick reading at the first glance)

For english speakers, the following is necessary :

Tableau 2 : Mesures crâniennes et âge des enfants fossiles
Table 2 : Cranial measurements and age of the fossil children

On the left side the names of fossil skulls (the Neanderthals in brown), and to the right their age.

GRAPH 5 : Comparaison des capacités crâniennes entre enfants fossiles et modernes
GRAPH 5 : Comparison of cranial capacities between fossil and modern children

You may notice that Cro-Magnon, the first hybrid (those that are not highlighted in brown) also has a large cranial capacity compared to modern children.

Quoted from the study:

In The GRAPH 5, we propose a comparison of cranial capacities between fossil and modern children. We find that the capacity of the skulls of these children : Pech-de-Azé, La Quina, Engis 2, Qafzeh 11, and Sungir 2, integrate perfectly among the modern children as they are inside the variability area which is that of two standard deviations. For the Sungir 3 child, the values ​​of the cranial capacity are slightly above the upper limit of variability. However, the cranial capacity of the Teshik-Tash child is far above the upper limit of variability due to the great length of the skull. It is the oldest child of the Neanderthal series.

This study is accompanied by this graph illustrating our problem in a very clear way, so I give you it in comparison to the graph from the study of M.Hublin.
Neanderthal skulls of children are indeed allowed in the upper limit of the variability of modern children (their range of children included main ethnic groups, a roughly equal proportion), as we expected already some fossils may leave curve, but only from the top.

The most important for us, is especially that the curve starts at two and a half years with, for the Neanderthal example the skull of the famous Pech de l’Aze child. It should be noted here that the cranial capacity was assessed, as the most serious way, since it is precisely the subject of the study, approximately 1200cm3.
If we take our Neanderthal child with a average cranial capacity of 423.5 cm3 estimated by Gunz et al., we get a difference of 776, 5 cm3 between birth and 2 years and a half.
Of course it is a fast evolution, but not necessarily faster or different in shape from the modern humans, since we lack, for comparison, a one year old Neanderthal child. We have the birth and two and a half years and the evolution curve between these two points seems to follow, or seems to have have followed, we can not know, a dramatic vertical change as modern humans, to continue after with a slower progression.

What Mr. Hublin seems to suggest is that the sample of our Pech de l’Azé child is a year old, in this case these claims could possibly be true, but even he does not object to the age of the child of Pech de l’Aze (age group 3, he lacks an age group 2 individual, that means one year old among the Neanderthals).
The evolution of the brain of a Neanderthal child therefore follows the so-called classical growth curve with a “globularisation”phase between birth and about two years. The fact that the Neanderthals brain growth is included in the high part of variability of modern child or leave sometimes this variability area is explained by the fact that Neanderthal infant, child, adolescent, or adult has an average cranial capacity that is larger than the modern humans.

Between the Moustier 2 and Pech de l’Azé, there is almost 800cm3, so the curve should, on the drawing by M.Hublin, rise as much as that of the modern man, and even more, it should paradoxically (maybe) be more modern, and it actually slowing down after the age group 3 but maybe already after the age group 2 (1 year). What is the meaning of this drawing, and why is Mr. Hublin claiming that the Neanderthal skull follows the same development curve than the skull of a chimp? The fact that the brain development of a chimpanzee go faster is one thing, but the chimp brain is also incredibly small and the rapid development is therefore obviously not a surplus. Proportionally, it is growing faster, but in terms of size, the human one wins absolutely, indeed, the adult chimpanzee has a cranial capacity which ranges from 275 to 500cm3, roughly the same than a human newborn (modern human or Neanderthal)!

d. The development of the brain in the autistic child

Regarding autism, his statement can be understood in the sense that some autistic brain develops actually faster than normal children. Faster is however a term that, in my opinion, is not really appropriate, because these autistic brain does not grow only faster, but they are also, at the end of their development, generally larger and more heavy. Excess in development appears in the young age, especially before the age of two years. It actually looks like the Pech de l’Azé child which has a surplus of development compared to the average of modern children (a surplus that he had already, in part, at birth). However, while nothing in Neanderthal population, is suggesting that the brain growth slower than among modern human after this phase (the curve follows the same shape, or surpasses it, to reach a larger brain), some studies suggest that the autistic brain growth would, on average, slower after a certain point, so to get a brain, sometimes bigger, sometimes normal (but never smaller).

Regarding the rapid development, the studies are in agreement. Concerning the evolution after that point, but also the size of the head of autistic child at birth, the studies are in contradiction, but this contradiction can be explained by the race of the participants or the type of autism (autism alone or autism with mental retardation or other disease) since autism comes in 50% of cases with mental retardation and / or a genetic disorder. It even seems that a slightly smaller head than the average among autistic children at birth can be one of the major difference between autism with and without mental retardation. I’ll add the relevant studies in the appendices page.

It seems that some autistic persons are actually representatives of the high part of the variability area of the cranial capacity in the so-called modern humans. The brain follow a slightly different pattern of development, with a peak of development before two years that is higher than the average, and then, the speed of development is slowing down (the age where this slowing down begins is not established, and studies on this point are contradictory. It is possible that this age is different from one individual to another, but it is not in any case ever before 4 years), on average more than the so-called normal humans.
In adulthood, the brain size may be slightly bigger or equal to the average so-called normal human, but the brain development curve of an autistic person does in no way look the brain development of chimpanzees !

We must not confuse “re-descending compared to the average development” and “loss”. This autistic children does not lose any part of their brain, and they often keep even a large part of their advance.

When the compared individuals (autistic and non-autistic) have as only difference autism (and not the gender or IQ), there is in any case no re-descent below the curve of “normal” children actually, the additional growth is made within the two first years, but it is a surplus. The curve does not exactly follow the growth curve of normal children, and thus they “lose” a part of this surplus, but the size of their brain is still above that of normal children. We can clearly observe that the development of the parietal lobes is not “truncated” among autistic persons as Mr.Hublin had suggested in Neanderthal, and it is unlikely that this is the case in the Neanderthal child, whose head shape around the temporal lobes in childhood is almost the same as in modern humans, as indicated by the reconstructions of Mr.Hublin:

http://homepages.rpi.edu/~calhop/Creedence_tapes/neanderthal.pdf

Modern and neanderthal babies skull

Modern and neanderthal babies skull

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315057/

We observed generalized cerebral cortical enlargement in individuals with ASD (Autism Spectrum Disorder) at both 2 and 4 – 5 years of age. Rate of cerebral cortical growth across multiple brain regions and tissue compartments, in individuals with ASD, was parallel to that seen in controls, indicating that there was no increase in rate of cerebral cortical growth during this interval. No cerebellar differences were observed in ASD. After controlling for TBV, a disproportionate enlargement in temporal lobe white matter was observed in the ASD group. We found no differences in cortical thickness, but an increase in an estimate of surface area in the ASD group compared to controls for all cortical regions measured (temporal, frontal, and parietal-occipital).

Autistic brain

Autistic brain

Mean group differences are reported in Table 3 for ASD versus controls, and in Table 4 for autistic subjects versus the TYP and DD control subgroups, respectively. Subjects with ASD had significant enlargement in TBV, total tissue volume (TGV+TWV), TGV, and TWV, with a 9% enlargement of cerebral cortex volume compared to controls. Cerebellar volume did not differ significantly between the ASD and control groups. Subjects with ASD had enlargement in both gray and white matter volume for all cortical lobes, but only temporal lobe white matter volume remained significantly enlarged in comparison to controls, after controlling for TBV. This same pattern of generalized volume enlargement in the ASD group for the cerebrum and cortical lobes was also seen in the TYP and DD subgroup comparisons (see Table 4).

table3

Table 3

Table 4

Table 4

An another study :
http://www.youtube.com/watch?v=k7sYLtq0_F8

http://www.sciencedaily.com/releases/2011/11/111108200710.htm

Brain and head overgrowth in children with autism and neural dysfunction are evident at young ages in multiple brain regions, including the prefrontal cortex (PFC), that are involved in higher-order social, emotional, communication, and cognitive development. “Therefore, knowledge of the neural basis of overgrowth could point to early causal mechanisms in autism and elucidate the neural functional defects that engender autistic symptoms. In the first magnetic resonance imaging (MRI) report of early brain overgrowth in autism a decade ago, it was theorized that excess numbers of neurons could be an underlying cause, perhaps due to prenatal dysregulation of proliferation, apoptosis [cell death], or both. However, the neural basis of early overgrowth remains unknown and can only be known from direct quantitative studies of the young postmortem autistic brain,” according to background information in the article.

Eric Courchesne, Ph.D., of the NIH-UCSD School of Medicine Autism Center of Excellence, La Jolla, Calif., and colleagues examined whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. The study included postmortem prefrontal tissue from 7 autistic and 6 control male children, ages 2 to 16 years, which was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006.

The researchers found statistically significant differences in neuron counts in the PFC in the autistic children compared with controls. There were 79 percent more neurons in DL-PFC in the autistic cases compared with the control cases and 29 percent more in M-PFC. The average DL-PFC count in the autistic children was 1.57 billion neurons compared with an average of 0.88 billion neurons in control children. The average M-PFC count in the autistic group was 0.36 billion neurons compared with an average of 0.28 billion neurons in controls. “Together, these 2 subdivisions gave a total combined prefrontal neuron count that was 67 percent greater in the autistic children compared with controls,” the authors write.
The researchers also found that the brain weight in the autistic sample deviated from normative average weight for age by 17.6 percent, while control brains deviated from age-based norms by 0.2 percent.

“Our sample of autistic children was not large enough to statistically examine brain-behavior relationships. Future studies with many more cases of autistic children might reveal important relationships between neuron counts and symptom severity or intellectual ability,” the authors write.

“To our knowledge, this study is the first direct quantitative test and confirmation of the theory that a pathological overabundance of neurons in critical brain regions is present at a young age in autism. Because cortical neurons are generated in prenatal, not postnatal life, pathological overabundance of neurons indicates early developmental disturbances in molecular and genetic mechanisms that govern proliferation, cell cycle regulation, and apoptosis. Therefore, the finding has significance for understanding the etiological and neural development and functional origins of autism.”

An another article on the same study :

http://www.nhs.uk/news/2011/11November/Pages/baby-brain-clue-to-causes-of-autism.aspx

About Autism, many observations are made, but few causes are found. They recognize genes involved in some cases of autism, a different growth of the brain and a head that is often larger, there is also some chemicals features in some autistic persons, but nobody has found THE reason of autism and this, probably just because there is not ONE reason of autism.

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