Limbic Valence

I have been recently arguing that such things as Natural Rights etc are reflective of the genetic structure of the limbic system. Furthermore, the hippocampus is a key element in that system.

In a recent paper in Genes the authors note:

The hippocampus is a brain region important for learning, memory, and emotional responses  In addition to brain development that occurs during the prenatal period, significant brain growth and maturation including synaptogenesis, dendritic growth, and glial cell proliferation also occurs during the first few years of life. Environmental insults during this period can have lasting effects on brain structure and function, with the hippocampus displaying high susceptibility to the effects of early life environmental insults. Previous studies have identified altered gene expression in the hippocampus of individuals with altered functions, such as reduced learning and memory or  behavioral changes. However, the cellular mechanisms responsible for altered gene expression in response to early life environmental insults are largely unknown.

The field of epigenetics focuses on gene expression and phenotypic changes that develop without changes to an individual’s DNA sequence. One of the most well understood epigenetic marks is DNA methylation, which occurs predominantly at CpG sites—defined as a cytosine nucleotide followed by a guanine nucleotide—throughout the genome. DNA methylation levels play an important role in gene expression and are affected by environmental exposures during development. Due to the known relationship between environmental exposures, DNA methylation, and gene regulation, it is expected that aberrant gene expression resulting from altered DNA methylation levels can help explain phenotypic changes induced by environmental exposures. However, extracting multi-omics signatures from high-dimensional heterogeneous data presents unique analytical challenges because these data belong to the p>>n class of problems where the number of features is orders of magnitude larger than the number of samples in the study. Likewise, the common univariate approaches for ranking feature relevance fail to capture complex multivariate relationships and apply feature-ranking criteria unrelated to the model accuracy. These approaches can be unstable and result in high false discovery rates and unreproducible predictive models

This is an interesting result. The limbic system, early development and epigenetic impacts. Genetic, and clearly epigenetic factors impact the hippocampus as well as the other elements of the limbic system. The limbic system is what makes us rational/irrational creatures, it controls emotions, etc.

Lysenko and The Soviet Academy

Graham has written a wonderful book on Lysenko and the Russian School of Genetics during the Stalin era. Lysenko viewed inheritance in the sense that certain characteristics could be handed down in generations based upon environmental factors experienced by parents. That is the change in a genetic makeup was not solely due to genetic changes per se. He could turn summer wheat to winter wheat by getting it used to a change in weather. Thus he did not need a genetic alteration but an environmental alteration was sufficient. In a sense the concept did play into the hands of the Marxist reasoning.

Graham blends the understanding of epigenetic changes that are currently being understood with the ideas of Lysenko and asks if this new understand then justifies Lysenko's ideas. On the other hand, Graham details Lysenko's way of dealing with his academic adversaries often resulting in their imprisonment and demise. The current understanding of gene expression and thus phenotype is that genes can be turned on and off by such epigenetic factors as methylation. Methyl groups bind to the nucleotides and also suppress expression directly by blocking the gene or indirectly by blocking transcription factors.

This is somatic epigenetics. Germ line epigenetics, parent to child has also been observed. Namely effects on the parent causing epigenetic changes can be handed down to the child, where it was assumed that the methylation of certain bases was eliminate but somehow they can be preserved. Thus, in a simplistic sense, an environmental change imprinting the parent can imprint the offspring. This may or may not be consistent in a broad sense with Lysenko but the author discusses it in some detail. Graham's discussion is limited as one would expect in a short book of this type but he does explain some of the issues well including the event of the "Dutch Winter", an epigenetic benchmark.

Graham has a wonderful discussion of his opportunistic meeting with Lysenko at a lunch table in the Russian Academy, and the brief attempt to elicit some explanation from Lysenko. Lysenko was as one would expect defensive since this occurred after he was taken down from his perch yet retained his academic credentials. This discussion is quintessential east meets west based upon my personal experiences in Russia when first meeting some notable. It was clear from Graham's description that Lysenko was still wary especially since Graham had been critical of him in Graham's prior writings.

Graham also presents a clear and coherent discussion of the players in this tragedy, the geneticists following the true path and how Lysenko and his actions resulted in their fall.

The only point that would have been useful to explore would be the need by the Marxist theorists to have a Lysenko position versus a Darwinian one. I had seen this battle with the probabilists. Marxist theory is deterministic and probability is its enemy. Yet many probabilists managed to work and prosper. Individuals like Gnedenko, Kolmogorov, Stratonovich, Markov and others developed the basis for stochastic processes that we see used in fields as broad as finance with the Black-Scholes theorem in options trading, a thought anathema to the Marxists. Graham does provide some insight but it would be worthwhile to have a more in depth discussion of this potential conflict.

Overall the book is an excellent addition to understanding both the Russian Academy and its functioning, the Stalinist management of the overall society, and a petri dish model of Academic infighting. It is very worthwhile for those seeking to understand both Russia as well as the politics of Science, albeit in a different vein.

Bacterial Immune System

Each time one finds a new and innovative biological mechanism one finds another twist and turn. CRISPRs have been explored for a short while but they were understood to be an immune system for bacteria against viral phages. But now there is evidence that they are also used against antibiotics.

Eureka states:

The CRISPR system has attracted considerable attention for its potential uses in genetic engineering and biotechnology, but its roles in bacterial gene regulation are still surprising scientists. It was discovered by dairy industry researchers seeking to prevent phages, viruses that infect bacteria, from ruining the cultures used to make cheese and yogurt. Bacteria incorporate small bits of DNA from phages into their CRISPR region and use that information to fight off the phages by chewing up their DNA. Cas9, an essential part of the CRISPR system, is a DNA-chewing enzyme that has been customized for use in biotechnology. 

The interesting question is that CRISPRs must have developed this capability in bacteria over the past fifty years or so. If so this adds a dynamic to CRISPs that is quite startling.

Methylation and Ancestors

Every time we learn more about genes and their operations we add complexity. Epigenetics has added a dimension which oftentimes surpasses much of what we have learned before. In a recent Science article the authors examine the epigenetic differences in humans and their ancestors. They state:

Ancient DNA sequencing has recently provided high-coverage archaic human genomes. However, the evolution of epigenetic regulation along the human lineage remains largely unexplored. We reconstructed the full DNA methylation maps of the Neandertal and the Denisovan by harnessing the natural degradation processes of methylated and unmethylated cytosines. Comparing these ancient methylation maps to those of present-day humans, we identified ~2000 differentially methylated regions (DMRs). Particularly, we found substantial methylation changes in the HOXD cluster that may explain anatomical differences between archaic and present-day humans. Additionally, we found that DMRs are significantly more likely to be associated with diseases. This study provides insight into the epigenetic landscape of our closest evolutionary relatives and opens a window to explore the epigenomes of extinct species. 

This is an interesting first step well worth the following!

One suspects that the more we understand methylation, miRNAs etc the better we can understand some of the vagaries of life.