Evidence for evolution of a key autism-linked gene

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When i was reading about HAR (Human Accelerated Regions) on wikipedia http://en.wikipedia.org/wiki/Human_accelerated_regions, basically genetic regions that are normally conserved throughout vertebrate evolution but strongly changed in the human lineage, suggesting a strong selection pressure for these genes, i noticed that HAR31 (so one of the less significant regions but still significant enough), containted AUTS2, one of the mayor autism susceptibility regions. Some further research showed that the recently sequenced neanderthal genome did NOT have this gene as a HAR, rather the neanderthal genome had a gene copy (allele) much closer to the ancestral chimpanzee-human common ancestor version. So i think this sort of refutes any notion of neanderthal genetics causing autism (although all non-african populations evidently do have a few % neanderthal genes, an important example is 70% of brainsize regulating alleles having come from a neanderthal lineage in non-africans.). so what does this mean? it means that autism-like cognitive traits (most all HAR's are related to enhanced cognition) were selected for in our recent lineage, possibly only within the last 200.000 years (transition between fully modern brain volumes and fully modern intellectual behaviour?). according to a mendelian genetics database in the human lineage there is a section of AUTS2 which appears to have recently acquired almost 300 consecutive SNP's (single letter changes), suggesting a strong selective sweep. Anyone got any interesting interpretations of this?

Looks like something has caused the region of the genome known as HAR to experience a lot of changes in the last 200,000 years...what that is we haven't discovered...

The presence of an autism causing gene may be present in modern humans and not human ancestors simply due to the fact that modern humans are better able to compensate for other short comings and so we are more likely to propagate genes which cause potentially negative effects.

In pre-modern times, carriers of such genes, who were also affected, were more likely to die before they were able to pass on the gene when it did arise.

But then again, it may be allelic with the genes associated with modern human brain size regulation and so on.

Most of those who have made significant contributions to mankind were only able to do so because they thought a little differently than the majority of mankind. These are the giants on who's shoulders we stand. Strangely enough, many of these individuals never had any known offspring.

Ana : there is not region called HAR, there are 49 ones. (all seem to be protein coding genes with an unusually high amino acid substitution rate), most HAR's are shared with neanderthals but this specific one related to AUTS2 (i presume in other mammals AUTS2 can cause autism too but is completely selected agains in most all cases) only appears to have undergone significant changes in our lineage.. also, an even more significant HAR is related to schizoprenia, which confirms another theory of mine that schizophrenia in its non-disordered form was positively selected for. Interestingly the brainsize regulation gene does not appear to have undergone as radical a change as you'd expect from what i've been reading. It seems that gene has been evolving steadily in the whole primate lineage (and of course, ever since the first mammals with their presumably small neocortex (shrews, desendants of the common ancestor of all placental mammals, have a very tiny cerebral cortex, even for their size (1 million neurons, 11mm² surface area, compare that to humans with their 200.000mm² surface area and over 20 billion neurons, even when adjusted for body size we outshine them by a decent factor.) so, maybe brain volume was important, but true modernity was caused by further reshaping of the brain (which continues to this this day, if you look at charts of human brain volumes, while the total average has gone down, there is still a trend towards exponential brain expansion the last 200.000 years (in charts, there is a steady increase until 200k years ago since 2 million years ago, then suddenly there is a sharp acceleration in volume expansion)
So in short, our brains are evolving like hell, although africans seem to be closer to ancestral cognitive abilities (touchy subject i know.)

My theory is human accelerated region genes are highly succeptable to mutation meaning they are unstable and vulnerable which could explain autism, schizophrenia, etc. appearing in the human population.
I realize HAR is not a name but an acronym. HAR stands for Human Accelerated Region.
Fascinating area of study, DevilInside, thanks for posting about this!

you would be correct, i skimmed the paper on HAR from 2006 and it did say these regions were highly mutatable, however since they are normally conserved these mutations have been selected against in other vertebrate lineage (remember vertebrates are an incredibly large monophyletic grouping, so we are definetely uniqe in some ways)

That's the fascinating part, DevilInside. Why us?

walking upright, descendance of our vocal chords + opposable thumbs and modification of the hands seem to have allowed for an unprecented evolution of genes related to brainsize and cognition, i mean primates in themselves are already different from other lineages in this respect, but whatever mutation caused us to start having a tendency to walk upright is most likely what happened around the split between our lineage and that of the chimp and lead us down this wonderful (and absurd) path. What's even more amazing is that the most significant part of that brainwise was from 2 million years ago until today, with an acceleration a few 100.000 years ago (neanderthals had larger cranial volumes, but perhaps a few less cognitive enhancements we now have.)

I was of the understanding, that "pressures" tend to reduce the sorts of genetic variability, which prevent birth defects, and am admittedly unclear, as to how autistic traits would be advantageous to survival.

An example, which made sense to me, was a giant shark taking a chomp out of a school of minnows. This instantly resulted in less genetic material, and the ones which got away were not necessarily more "fit," but may have simply escaped at random, through no special capability of their own.

You're discussing survivors with autistic genes.

In general, do their offspring seem to be outpacing the neurotypical in any observable way? If so, how?

Respectfully, we don't look at a happy person, and ask whether he was feeling pressured.

IMHO, it's pressures, which drive species to extinction.

I appreciate that my worldview may not be what you were used to.