Another ancient DNA surprise: history of the New World Arctic people

It has been widely noticed repeatedly that every ancient DNA research result has been a great surprise, starting from our 2008 paper or the first post on this blog back in 2007. The latest is a Science paper today The genetic prehistory of the New World Arctic. The surprises here are 1) again (and again and again.....again....) that there is no genetic continuity between local people living today and those locals in the past(>2000 years old); again and again ... replacement rather than regional continuity, following exactly the footsteps of the Out of Africa model superseding the Multiregional model. 2) no sex between people who lived side by side;"Elsewhere, as soon as people meet each other, they have sex," says Willerslev. "Even potentially different species like Neanderthals [and modern humans] had sex, so this finding is extremely surprising." (3) extreme low genetic diversity in mtDNA in ancient Paleo-Eskimos. "I can't remember any other group having such low diversity," says Willerslev. For quote by Willerslev, see see this news piece.

Well, just like we said in our post on the 400K year old Heidelbergensis DNA, it would be a complete surprise if the field of ancient DNA as it is presently practiced could produce any sensible and non-surprising result consistent with common sense and fossil and cultural records. When you use noninformative DNAs to do your analytic work, what can you expect other than meaningless trash.

Of course we are working hard to reinterpret these newly published DNA sequences and we should soon publish our results (constantly delayed by newly released DNAs needing reinterpretations) that should be a very pleasant and intellectually satisfying surprise to all. For example, as our new analysis shows, the iceman Otzi was indeed most closely related to the local living Italians as common sense would expect, rather than to remote island people the Sardinians as is now mistakenly concluded by the literature. 

Secrets of the creative brain

There was a recent good article on creativity,Secrets of the creative brain.  A related blog post, The Psycholpathology of Genius.

We are actively working on the genetic basis of complex traits and the most complex is obviously creativity and intelligence. According to the threshold theory, Creativity is not IQ only and a score of 120 is the threshold. Lower or much higher than than that may hurt creativity.

Some quotes from Secrets of the creative brain:

One possible contributory factor is a personality style shared by many of my creative subjects. These subjects are adventuresome and exploratory. They take risks. Particularly in science, the best work tends to occur in new frontiers. (As a popular saying among scientists goes: “When you work at the cutting edge, you are likely to bleed.”) 

I’ve been struck by how many of these people refer to their most creative ideas as “obvious.” Since these ideas are almost always the opposite of obvious to other people, creative luminaries can face doubt and resistance when advocating for them. As one artist told me, “The funny thing about [one’s own] talent is that you are blind to it. You just can’t see what it is when you have it … When you have talent and see things in a particular way, you are amazed that other people can’t see it.” Persisting in the face of doubt or rejection, for artists or for scientists, can be a lonely path—one that may also partially explain why some of these people experience mental illness.

One interesting paradox that has emerged during conversations with subjects about their creative processes is that, though many of them suffer from mood and anxiety disorders, they associate their gifts with strong feelings of joy and excitement. “Doing good science is simply the most pleasurable thing anyone can do,” one scientist told me. “It is like having good sex. It excites you all over and makes you feel as if you are all-powerful and complete.” This is reminiscent of what creative geniuses throughout history have said. 

Many creative people are autodidacts. 

Many creative people are polymaths, as historic geniuses including Michelangelo and Leonardo da Vinci were. 

Creative people tend to be very persistent, even when confronted with skepticism or rejection. 

Some people see things others cannot, and they are right, and we call them creative geniuses. Some people see things others cannot, and they are wrong, and we call them mentally ill. And some people, like John Nash, are both.

Testing the infinite sites assumption

We presented the following poster at the "1000 genomes and beyond" meeting, Cambridge, UK, 24-26, June 2014. We are also going to present it in the ASHG 2014 meeting in Oct 2014, San Diego. 

The bottom line is that there are very few neutral or junk DNAs in the human genome, at least when one examines the genome by using experimental approaches. (a new paper of ours on disproving the neutral theory by using an experimental approach has just got published here, titled Scoring the collective effects of SNPs: associations of minor alleles with complex traits in model organisms.)  All previous studies used only bioinformatics approaches. Their conclusions of less than 10% functional genome are based on UNCERTAIN assumptions and therefore are mostly meaningless. The field must realize that it is time to stop such senseless researches based on senseless assumptions. We should either do experiments without any prior assumptions or if we have to, we must only use a priori sound intuitions as our assumptions.

The abstract, introduction and discussion of the our poster are posted here. The poster can be downloaded from my lab website.

  Abstract The infinite sites model of the neutral theory is a fundamental assumption underlying nearly all population genetic and phylogenetic studies today but has yet to be properly tested. We here tested it from two novel perspectives using the 1000 genomes dataset. First, we examined the genetic diversity patterns of different human populations using a variety of different types of SNPs, such as a random set of SNPs representing genome average, stop codon, nonsyn, syn, etc. Patterns shown by a random set of SNPs are expected to be similar to those shown by known functional stop codon SNPs, if most SNPs are not neutral. In contrast, neutral SNPs should show a most different pattern from stop codon SNPs. Second, it has long been well known that most genetic variations are shared among different human groups, which has been interpreted from the infinites sites perspective to mean few genetic differences among the ethnic groups (Lewontin, 1972). But the possibility of saturation or independent mutations to account for this phenomenon has yet to be examined and excluded. We compared the number of shared SNPs in DNAs of different evolutionary rates among different human populations to see if shared SNPs are in fact a result of independent mutations or saturation and hence more common in fast evolving DNAs relative to slow ones. We found that a random set of SNPs are just like the stop codon SNPs in showing Africans to have the largest genetic diversity. Shared SNPs are enriched in fast evolving DNAs. These results suggest that the vast majority of the human genome do not follow the infinite sites model.

     Introduction  Molecular studies have so far relied on the Neutral theory and its infinite sites assumption. The Neutral theory was originally inspired by the so called molecular clock which was in turn inspired by the first and most remarkable result in molecular evolution, the genetic equidistance result that sister species are approximately equidistant to a simpler outgroup. In recent papers, we have shown that the equidistance result has been incorrectly interpreted by the molecular clock with grave consequences on phylogenetic studies: nearly all past studies have used non-informative DNAs assumed to be neutral but have now been shown by us to be under selection (Hu et al, 2013, Huang, 2010). The neutral theory was mistaken right from its inception. We have developed the maximum genetic diversity (MGD) hypothesis to absorb and supersede the neutral theory (Hu et al, 2013). From this more correct/complete theoretical perspective, we here tested whether the infinite sites model holds for the majority of the human genome as is commonly assumed.  

       Discussion: mutation rate, sequence conservation, and neutrality

       The results suggest that the vast majority of human genome do not follow the infinite sites model and are not neutral. Only a very limited sites: the non-syn slow evolving SNPs as defined here, behaved uniquely among all the SNPs examined and appear to be neutral or follow the infinite sites model. They are not deleterious as they are different from stop codon SNPs.  They are also not under positive selection as positively selected genes tend to be fast evolving.  To the dramatic difference between slow and fast evolving DNAs as shown here, we cannot come up with a meaningful explanation using any known schemes other than the recently proposed idea of maximum genetic diversity. 

       Variation in mutation rate in different regions of the human nuclear genome may exceed 1000 fold.  That a gene is slow evolving could be due to at least two reasons.  One is being located in a region of the genome with slow mutation rates.  This however may not apply to the difference in mutation rates between non-synonymous and synonymous sites of the same gene as found here.  Alternatively, most mutations may hit functional sites and be negatively selected by the need to maintain the internal integrity/order of a biological system. It would take many mutations and hence a long time before a neutral site is hit, thus giving the appearance of a slow mutation rate. Since changes in such neutral sites take long time, they may be too slow to meet adaptive needs to be under positive selection.  Given the apparent slow rate and absence of positive selection, they are also unlikely to reach excess levels to cause harm or be under negative selection. 

        Hence, sequence conservation per se may not automatically indicate functionality of variants within such sequences as is commonly assumed.  Less conserved sequences are more important for adaptation to external environment, while the more conserved ones are important for internal integrity of a system. To a virus or bacteria facing elimination by human medicines, the fast evolving parts of their genome is far more critical/functional to their survival than their more conserved parts. The popular assumption of neutrality/non-functionality for the less conserved parts of the genome overlooks their fundamental function in quick adaptation.