Proving the Neanderthal theory with 23andme

[mamasatya]

OK let's start from the beginning:

Claim 1: All species have a cannibalism option
Claim 2: All cannibalistic species have a mechanism for differentiating 'kin' from 'prey' where kin and prey are the same species

http://www.popsci.com/scitech/article/2 ... s-siblings

http://www.sciencedaily.com/releases/20 ... 092513.htm (Imaging Reveals Key Metabolic Factors of Cannibalistic Bacteria)

How does a microbial mat decide which bits of itself to nibble on when ambient nutrient levels are low, or expected to get even lower..?

[mamasatya]

Something here needs to be resolved, Your paper states:

"Australopithecus is most likely a descedant of Oreopithecus, and lived in Africa 3 million years ago. It still was bipedal, but it is unlikely they are direct ancestors of Homo because of the back-evolution to an arboreal life-style. Alternatively, it's possible that Pan is not at all very closely related to Homo and that the similarity in mitochondrial DNA is caused by climatic selection on the mitochondria."

However you see fit to reject the suggestion that 'climatic selection' may be responsible for the similarities between neanderthal and asperger dna?

What's the difference?

[Sophist]

This is assuming that the roots of autism lie solely in genetics rather than epigenetic mechanisms.

Not so. Currently, the 23andme test can only explain 10% of neurodiversity. We still lack 90%. OTOH, the present result is not evidence that 90% of neurodiversity is environmental or epigenetic. Other possible reasons for the low amount is that 23andme only uses SNPs, and not CNVs. A test that compared CNVs could potentially get a much higher correlation that might explain much of neurodiversity. About the only thing we know is that at a minimum Neanderthal DNA can explain 10% of neurodiversity. Then we have the difference between ASD diagnosis, and neurodiversity as defined by Aspie Quiz. They have a little above 0.8 in correlation, but that means that they don't share 30-35% of the traits. These 30-35% are probably mostly environmental issues.

What I meant is that is not how DNA nor the cell works. There is far more phenotypic diversity that lies within the machinery of the cell above the DNA. That includes literal epigenetic mechanisms such as heritable histones and methylation patterns, but that also includes lipid construction, various endogenous and foreign RNAs, and loads more effectors than even I know about. An extremely large portion of inheritance does not lie within the DNA itself. And a large portion of phenotypic variation is "inherited" simply by nature of common environment, generation by generation, not by something inherent to the organism itself, other than plasticity.

The concept of development and diversity does not work like the media, or even many scientists, portray it. And I realize it's difficult for people who haven't studied this area of science to understand the general concept. But I've studied enough to know how MUCH I still don't know; but I generally know what I don't know. And I'm telling you, and anyone else who has similar misconceptions, placing such emphasis on DNA is not how biology truly works. I'm just advising caution on making assumptions based on a generalized and inaccurate concept of DNA-centered inheritance. DNA makes a good molecular clock of general relatedness, but that is on a really grand scale, species by species. It doesn't tell you how the person you're looking at in front of you came to be.

If there is indeed some relation between Neandertal DNA within the human genome and autism, then you're missing tens of thousands of years of history in between. Are you assuming that the rates of autism have been constant throughout, medical issues like birth fatality aside? Because at present, research does not suggest that to be the case, even in lieu of broadening definitions and greater awareness. If there is indeed a link between cross-breeding of Neandertals and humans and then autism today, how do you explain the changing rates? What is it about the environment and that Neandertal DNA that might be changing our populations' phenotype, autism with it?

I'll tell you something: in Manny's work looking at microscopic structural changes of the cortex just within the last generation, there have been considerable changes in the tail ends of the human spectrum measured. Changes in minicolumnar phenotype, reflective of more big brains and more smaller brains, the extremes of that spectrum, have changed just within 20-30 years. One generation.

In addition, the Neandertal SNPs associated with ASC: what is the proposed function of some of these genes? Why and how are they relevant to autism? Just some questions I had.

This is assuming that the roots of autism lie solely in genetics rather than epigenetic mechanisms.

Viewing genetics as a "cause" of anything reveals a poor understanding of biology and development in general.

Quite right! The way I look at it, it's like saying the blueprint for a building is the cause of a building (or the reason for designing it a particular way). Even if you could pour building materials and fuel onto the blueprint and have the building magically spring into existence (DNA works this way, sort of) it's still not the 'cause' of the building.

Sophist how do you feel about the 'cannibal / hypernutrition / weather / no more cannibals' suite of hypotheses for autism?

Sorry I missed this earlier. To be honest, I'm not familiar with the hypotheses, nor would I have much to hypothesize re some of these issues on my own accord. I don't know enough about cannibalism throughout metazoan evolution. Climate is an ever-present factor and undoubtedly alters phenotype of all individuals. Autistics wouldn't be immune to such effects. Hypernutrition: not sure. I definitely think many aspects of diet, particularly maternal diet during gestation, play roles in the development of ASC. For instance, there are some links between endocrine disruption, e.g., diabetes, and ASC risk. If the mother, for instance, has insulin resistance but keeps a carb-high diet, and the level of endocrine disruption has a positive link to severity of ASC, then diet could definitely drive a more severe autistic phenotype. But for "hypernutrition". What are we getting too much of? Many times, in today's society, I think we are getting too much of certain things but then too little of others. So is "hyper" really accurate?

These variables are far too complex to simply look at each one alone. The relationship is the most important unit for analysis. Though we give autism a single label, it's extremely heterogeneous. As heterogeneous as any two strangers taken from the street at random. And the autistic phenotype is dynamic, not static.

In order to assess situations, it is initially necessary to simplify things to a single effector and test a hypothesis. But autism isn't that simple. It's many things. There are as many forms of autism as there are autistic people. It's a similar argument in how to define a species, or how to define life itself. That's because such concepts are okay enough for broad generalization but when you zoom in to take a closer look and test concrete hypotheses, the concept falls to pieces. Not dissimilar to Newton's laws of physics when looked at from grander or quantum scales.

I think we will continue to identify commonalities which include most of the autistic population. But I think as time goes on, we will learn more by defining exactly how all these people are different from one another. In such instances, in depth case studies may even be helpful, rather than broad studies that look at averages.

I wish rdos all the luck in the world; he's a good guy and a hard worker, as well as highly inventive. For my own part, I don't place my scientific faith in Neandertal DNA as a root of autism. That doesn't mean I wish him wrong. With his persistence, if there's real clout to his concepts, he'll eventually prove me wrong. And that's fine too. But for my current concepts of autism, Neandertals don't fit into the framework of how I understand the conditions.

[mamasatya]

'Hyper-nutrition' means an unusually good deal, food-wise, when compared to normal animals.

There are two sides to nutrition: The food you get, and your beliefs about the food you get.

What happens to a creature when it doesn't miss a meal very often, and this goes on for several generations? What happens to a creature which receives virtually complete nutrition daily for several generations? When these creatures have been dependant on certain faculties (the skill to evade predation may no longer be needed, the skill to win food from the pack is no longer needed - unless one has fever when young of course), what happens when these faculties are no longer required? Brain is expensive to build, it's surely the first thing to 'get loose' when the environment suggests part of it is no longer needed?

What about a creature's beliefs about nutrition? Maybe since this interglacial brought agriculture and with it, belief in great ability to provide for oneself through farming and storage and improved hunting techniques? Maybe your grandmother and your great-grandmother didn't ever have to experience fear of starvation, and that 'switched off' the genes for copying others in order to learn how to curry favour and win food?

Similar to the way famine is a risk-factor for schizophrenia, could 'not enough famines' be a causal factor in autism developing over a few generations? It would certainly fit with what we know about racial distribution in autism. White people have had full nutrition for longer on average than others, always seems to be the darker skinned people in the developing world who are left starving whenever food deliveries become too inconvenient.

Quite aside, I agree that we are Neanderthals, in the great cosmic game of 'what animal am I?' it makes sense to me to identify with the part of me that occupied the highest position historically in the food chain (before 'magical' methods became commonplace and human beings found their way to their current position being the least efficient 'eater' on the planet yet firm in the belief that it is higher than a lion!).

[Sophist]

I think you're placing far to much emphasis on the idea that there is a gene for food gathering or hunting, not unlike many non-geneticist scientists have proposed, for instance, the Foxp2 gene is a gene "for" language. As a neuroscientist who has seen how this protein is labeled throughout the mouse CNS, it makes sense that a knocking out this gene could affect such facilities as language, given its expression throughout subcortical regions and the lower layers of the neocortex. A gene translates into RNA which can be translated into a protein. That protein product is used for numerous faculties within the cell. There is no single gene for a given behavior or aspect of gross morphology. When thinking of what particular genes do, one needs to remain at the single cell, or at the very most, the tissue level. Not jump to gross behaviors. It isn't that genetic variation can't affect all levels of biology, but to simplify such complexity to Gene A causes Behavior B is grossly inaccurate. Gene A is actually used to code for various RNAs and perhaps ultimately a protein product. That's it.

Phenotype tends to precede genotype. Different demands on phenotype, what with an ever-changing environment, alter the restrictions placed upon the genotype. E.g., simians and the production of vitamin C. Since our line has gotten our vitamin C from fruit-rich diets, a mutation which prevents the production of the enzyme, L-gulonolactone oxidase, necessary for making our own endogenous vitamin C didn't matter. The phenotypic restraints on this gene were loose, allowing greater genetic variation: phenotype preceded genotype.

Probably one of the biggest changes having accompanied our agricultural lifestyle is simply our diets, which are extremely varied compared to what we used to eat and compared to what most animals eat; this variety drives our phenotypic adaptation even more rapidly because you are what you eat. You change the food source, you will change the animal and the constraints placed upon that animal.

That doesn't mean that changes in lifestyle accompanying the acquisition of food haven't changed us as well. It's changed us in many ways. For instance, we are no longer nomads but are living in large urban or suburban societies most often. This means we tend to pick up fewer parasites but that we do contract more contagious bacteria and viruses from our close neighbors or family; this alone alters the phenotype of our immune system because different branches have developed to deal with these different categories of pathogens. The battles of our immune system with invading antigens greatly affects development generation by generation. From the grandest level, think of how the plagues selectively weeded out millions of us just within the last millenium. On the smaller level, prenatal infection could alter the person's phenotype permanently.

For my part, I suspect some of our changing environment and lifestyle may be promoting more cases of ASC. Some of these factors are more common in developed countries. There are undoubtedly many other factors weighing in as well.

As far as nutrition goes, I think we need to break down foods into categories rather than lump the whole of nutrition together and say there is "too much". There are numerous nutrients one needs. There are undoubtedly nutrients which we are getting less of nowadays even though you may call our society "hyper-fed". Do we have our fair share of carbohydrates and meat proteins? Yes, I'd say so. All you need to do is go to the corner McDonald's and you'll get more than enough of the pair of them. But other essential and nonessential nutrients may be in shorter supply. We have had a hate-hate relationship with fruits and vegetables which puts us at risk. Just because a person isn't hungry and has gotten more than enough carbs to satisfy their need for ATP, doesn't mean they're not starving in other ways. The other ways just won't likely kill you off as quickly.

The prenatal diet clearly predisposes towards certain aspects of metabolism, there's plenty of evidence to this effect, much of which is being used to study cardiovascular disease and the like. But when you're talking about "hypernutrition" you really need to be more specific. Chemistry is very specific and what KIND of deprivation or excess is important to define when attempting to predict development at the cellular level as well as the larger organism. "Hypernutrition" is extremely vague.

[mamasatya]

Words are as vague as you want them to be. Hyper-nutrition means exactly what you feel it must:

'greater-nutrition' or 'more-nutrition'.

Greater or more than what?

Greater or more it was before.

Before when? Now I'm vague. The king of England last missed a meal around 250 years ago (perhaps 12 to 16 generations).

That's a lot of 'entire generations' of creatures who have lost something very common to all animals: Nutrition doesn't happen every day.

How can we not at least hypothesise that such a change may lead to some change?

[Sophist]

What I mean is that it's vague to lump all food types into a single category of nutrition. If you mean, we're generally taking in more calories, or more carbs, or more protein, or...

I'm not trying to be argumentative, mamasatya, so I hope you're not reading that. I'm saying that, in order to understand how the biology of the cell is affected by general nutrition, you must be more specific as far as nutritive types to predict outcome.

[mamasatya]

Hell, no! I'm not trying to be argumentative either, and if it looks that way then I blame our asperger's!

Of course, stripped any negative emotional connotation, of course we are 'arguing' in the platonic sense.

Perhaps I've missed something rather important. One's evolutionary trajectory has a 'pilot'. All I can tell you for sure is that something that 'cares' is passed onto us through our gametes, so it's less than 1.47 GB whatever it is, and it's the thing which decides 'in which direction we should evolve' given the information and raw materials which it believes are available to it.

We are comfortable with the notion that random mutation alone comes nowhere even close to explaining the pace of evolution and a bit of elementary game theory tells us that there's less than a 0.001% chance that we don't have a para-generational pilot subroutine passed on through our gametes.

[Sophist]

I'm definitely not comfortable with the idea that random mutation and pure chance drives all aspects of evolution. There do exist many forms of nonrandom mutation, particularly in areas called CpG islands within the DNA. The nucleotide, cystosine, is much more prone to mutation than are the other nucleotides. These CpG islands, some argue, are most often remnants from retroviral DNA.

Retroviruses aside, for my part, I have often wondered whether the epigenetic patternings (methylation and chromatin) which directly control the transcription of DNA may not promote forms of mutagenesis.

I also don't think that, in order for phenotype to shift drastically that mutation is a necessity. I think more often mutation follows that phenotypic drift, as I mentioned before, simply because the constraints on DNA have also shifted, increasing the likelihood of genetic variation. Plasticity is engrained in the function of all the molecules that make up our body. Their functions are overlapping, often redundant, and highly networked.

If you think back on the animal form, many aspects of our morphology have changed over the millenia, but the general blueprint of bodily form has existed for eons. Which means that the difference between a human and a fish, while to our perception seems monumental, in the eyes of the molecules which determine our forms, are not that great after all. We're made up of similar modules, just put together a bit differently. All the really difficult biological chemistry was worked out hundreds of millions of years ago. The extreme variation in animal form we see today is simply variations to a common theme.

[rdos]

Just got my 23andme results. I have 2.8% Neanderthal heritage, and am of 100% European ancestry. My paternal line is irish / basque, while my maternal line is more "traditionally" European with a Middle East origin.

[Sophist]

That would be really interesting to do.

[rdos]

Update:

There is now 159 people of European descent (out of 91,000) that has provided reasonable 23andme scores. The correlation is 0.12, which means that p is about 0.05 that there is no relation between scores. There is a huge over-representation of NTs that have indicated their 23andme scores.

I posted a message about Aspie Quiz on one of 23andme's forums in hope of getting some more participants that know their Hn heritage estimation.

It was bad news that the correlation was that low, but maybe not entirely unexpected. In fact, the squared correlation might be similar to the estimated Hn ancestry according to 23andme, whatever that might mean.

[Sophist]

Update:

There is now 159 people of European descent (out of 91,000) that has provided reasonable 23andme scores. The correlation is 0.12, which means that p is about 0.05 that there is no relation between scores. There is a huge over-representation of NTs that have indicated their 23andme scores.

I posted a message about Aspie Quiz on one of 23andme's forums in hope of getting some more participants that know their Hn heritage estimation.

It was bad news that the correlation was that low, but maybe not entirely unexpected. In fact, the squared correlation might be similar to the estimated Hn ancestry according to 23andme, whatever that might mean.

Hopefully you'll continue to get greater numbers of people to participate so you can be more certain of your results, rdos. Best of luck!

[rdos]

I just wrote a new blog entry about the relation to 23andme. Link: http://blog.rdos.net/?p=105

It doesn't seem like the post to 23andme's forum is generating many answers (apparently 5-10 answers right now).

[BruceCM]

Sorry, can I just cut to the chase & find out what, if that theory is 'proved' it'd mean, anyway, please?