Some quotations from our Parkinson's disease paper just published in PLoS One

Some quotations from our Parkinson's disease paper just published in PLoS One:

Recent studies have begun to show that a much larger than expected portion of the human genome may be functional [24–29].

An organism can certainly accommodate some limited amounts of random variations within its building parts or DNAs, but too much random errors or mutations may exceed an organism’s maximum level of tolerable disorder or entropy. Thus overall level of randomness or minor allele amounts may be expected to be higher in complex diseases relative to controls.

In fact, while most bench biologists have thought otherwise, nearly all in the population genetics field still believe that most SNPs are neutral or that most minor alleles are minor because of random drift rather than because of disease-association.

The findings of higher MAC in PD cases is consistent with our intuitive hypothesis that a highly complex and ordered system such as the human brain must have an optimum limit on the level of randomness or entropy in its building parts or DNAs. Too much randomness over a critical threshold may trigger complex diseases. There may be only one unique and optimum way to build a complex system but there could be numerous ways to break it.While it may only take one single major effect error in a major pathway to cause diseases, it would require the collective effects of a large number of minor effect errors in many different pathways to achieve a similar outcome.

Application of the MGD theory on complex diseases, first success Parkinson's disease

We have a new research paper on Parkinson's disease in press in PLoS One

It is merely the first success of the MGD theory in solving complex dieseases problems.

Enrichment of Minor Alleles of Common SNPs and Improved Risk Prediction for Parkinson's Disease

Zuobin Zhu, Dejian Yuan, Denghui Luo，Xitong Lu and Shi Huang*

State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China

Abstract

Parkinson disease (PD) is the second most common neurodegenerative disorder in the aged population and thought to involve many genetic loci. While a number of individual single nucleotide polymorphisms (SNPs) have been linked with PD, many remain to be found and no known markers or combinations of them have a useful predictive value for sporadic PD cases. The collective effects of genome wide minor alleles of common SNPs, or the minor allele content (MAC) in an individual, have recently been shown to be linked with quantitative variations of numerous complex traits in model organisms with higher MAC more likely linked with lower fitness. Here we found that PD cases had higher MAC than matched controls. A set of 37564 SNPs with MA (MAF < 0.4) more common in cases (P < 0.05) was found to have the best predictive accuracy. A weighted risk score calculated by using this set can predict 2% of PD cases (100% specificity), which is comparable to using familial PD genes to identify familial PD cases. These results suggest a novel genetic component in PD and provide a useful genetic method to identify a small fraction of PD cases.

The universe evolves from simple to complex, concludes a physicist

I recently read the book "The Wrinkles in Time" by the Noble Laureate physicist George Smoot. I found his view of evolution of the universe from simple to complex to be in complete harmony with the facts of biological evolution. It seems to me there is a universal law of evolution that underlies all changes with time, regardless of life or non-life. There has to be one if nature is a coherent whole, which it obviously is. A few quotes from the book follow:

"[Steven] Weinberg muses... 'The more the universe seems comprehensible, the more it also seems pointless.' I must disagree with my old teacher. To me the universe seems quite the opposite of pointless... The more we learn, the more we see ... there is an underlying unity to the sea of matter and stars and galaxies ... we are learning that nature is as it is not because it is the chance consequence of a random series of meaningless events; quite the opposite. More and more, the universe appears to be as it is because it must be that way; its evolution was written in its beginnings-in its cosmic DNA, if you will.”

“There is a clear order to the evolution of the universe, moving from simplicity and symmetry to greater complexity and structure.”

“Accidents and chance, in fact, are essential in developing the overall richness of the universe. In that sense (although not in the sense of quantum physics), Einstein had the right idea: God does not play dice with the universe. Though individual events happen as a matter of chance, there is an overall inevitability to the development of sophisticated complex systems. The development of beings capable of questioning and understanding the universe seems quite natural. I would be quite surprised if such intelligence has not arisen many places in our very large universe."

“My speculation, however, is that because things become simpler as we near the moment of creation, there was only a limited range of possibilities; indeed, perhaps only one, with everything so perfect that it could have been no other way.”

Building Complexity and the main pattern in evolution

Building complex and robust machine may have more ways than just one. To have backups or overlapping systems is one way of doing it, the most stupid and awkward way. Instead of a single engine in a small plane, a more complex large plane may have 4 engines with 2 of them as backups. But is that the nature’s way for using DNA to build complex life? Do we have an extra heart or brain or any organ as pure backups? We don’t. If we don’t do it at the phenotype level, do we do it at the genotype level? Mostly not. Our gene numbers are much smaller than any one had predicted because complexity is not linked to an increase in gene numbers or in back up genes. Nature is smarter and does it by combinations of genes and by inventing novel and complex ways of using the same set of genes. And by giving extra functions to an existing gene. We create music not by inventing more notes, and the ways of using the existing notes are already infinite.

To add back up or overlap system is not really an increase in complexity. A four engine plane and a one engine plane has the same level of complexity as far as the engine is concerned. To have a back up brain, we still need to have a complex brain in the first place. For that to happen, disorder and random mutation must be suppressed. Who can imagine a brain capable of infinite order like mathematics could tolerate a level of disorder/randomness in its building blocks like that of a flu virus or any simple virus like early life forms at the beginning of evolution?

The backup way is also not sound for DNA based lives because, in my thinking, it increases the size of the genome and hence the target size for mutations. The backup copy is not expressed or functional in normal situations and therefore not maintained by natural selection and can easily lose its function due to accumulation of mutations. Thus, it is safe to predict that most paralogs of a gene in a complex organism have unique functions and are not just backups (plenty of data for this). The claim of complex organisms have more backups is simply wishful thinking and not supported by facts. Don’t we have a lot of single mutation diseases in humans?

For both genotypes and phenotypes, nature follows the rule of use it or lose it. Backups may have been invented once but would simply be lost due to disuse. Which is more effective in advancing complexity: to decrease mutations or to use backups? All facts of nature say the first. It is simply a reality that a theory based on that notion explains all facts whereas any theory that ignores it meets with countless contradictions.

There is an extremely common mistake in the evolution field that has infected the lay public. It is to ignore the main pattern and use whatever trivial pattern/facts to suit our theory and to invalidate the main pattern when our theory does not predict it. Given the infinite amount of data/facts of nature, any stupid theory can find some factual support, if the goal is not to account for the major patterns or is not to explain all without contradiction. The advance with time in complexity is the dominant pattern in evolution that is so obvious that it is hardly worth stating. (The best ancient Chinese thinkers from 5000-7000 years ago had always placed man above all else in nature and as equal in status to the creative power of nature namely yang/heaven and yin/earth as written in I-ching, which has been the foundation for the most long lasting civilization as well as the world view of the largest population on Earth. Ancients have much better intuitive sense than moderns simply because their focus is less distracted by trivial things or man-made artifacts, and intuition is the foundation of science.) But since our theory does not predict that, we ignore it and cite trivial cases of randomness to support no direction towards complexity. Or we use trivial and much less common cases of complexity loss like loss of limbs in snakes as evidence for no direction towards higher complexity. Or we cite abundant cases of no change in complexity during microevolution. But all these merely indicate that in addition to complexity increase, there is also another trend for stability or no change. One cannot use a single mechanism to explain two opposite major trends, which is what we are doing.

We ignore the order/beauty/complexity of our big brain, and cite examples of imagined imperfections in some organs as evidence for the imperfections of nature or evolution. We ignore the general perfection of the human body and cite examples of rare diseases to fault the power of nature/evolution. In every case, the main pattern says that nature/evolution is all good, order, and beauty. The existence of disorder, randomness, and ugliness are all trivial and minor patterns. It is simply nonsensical to focus on the minor patterns and to turn blind to the main patterns. We should not explain the trivial at the expanse of the main but that has become a habitual behavior to most followers of evolution, another simple indication that we are not on the right path in understanding the main pattern.