Quote: (02-19-2012 12:48 PM)WesternCancer Wrote:
I should have more to say about science/technology as I am going to school for that very reason. My genetics prof brought up a very interesting topic during class the other day.
http://en.wikipedia.org/wiki/Personalized_medicine
http://en.wikipedia.org/wiki/Pharmacogenomics
http://en.wikipedia.org/wiki/Pharmacogenetics
Basically once a receptor or pathway is found that responds to a certain drug such as HIV drugs, cancer drugs, antidepressants etc. The genes involved can be cloned into insect cells (they are easiest to work with in this case) and expressed. Then you treat the cells with different concentrations and different types of drugs and see what works best. (I think its measured by some sort of light expression) ie. which drug at a certain concentration will be the most effective to treat someone. The example my prof used was depression, many people go through a bunch of different drugs before they find the right one.
I haven't looked too much into the topic, but it seems interesting. With the increasing ease of sequencing genomes and the mass of data acquired from bioinformatics the only things I could see stopping this from being a very profitable industry are moral or otherwise concerns, made mostly by people who don't understand the process. (when most people think cloning they think making new humans or something, you just stick a gene into a vector, or in the case of PCR - used in paternity tests and criminology - you make copies of the DNA present)
Cool stuff. fruitflies is the insect of choice, as you well know. and i am guessing the flourescent protein used is the GFP. pharmacogenetics is the future, of course. personalized medicine. are you familiar with
epigenetics? Basically, it factually challenged mendelian and darwinian concepts all the way from principles of allele independent assortment to bolstering lamarckian hereditary view point. I kid you not. It shows just how much our environment goes into changing gene expression...and of course, hereditary qualities...that went beyond teratogenesis. It does all this WITHOUT NUCLEOTIDE SUBSTITUTION or changes and the effect extends to pecking order, social assignments and mating. I can see how some of these studies can be used to justify social engineering of some sort.(i can see roissy head exploding because it lay the smack down: Genes are important, but man can really rise above/sink below his genes with the right social condition, so to speak.)
anyways, i have attached the introductory paper i did on it...it was for a seminar class.(of course, i have deleted my name and the prof. name.)
EFFECTS OF EPIGENETICS MODIFICATION ON SOCIAL BEHAVIOR IN ANIMALS AND HUMANS
(deleted my name and professor name)
Abstract
Epigenetics is an exciting area of research that studies characteristics or traits that are expressed without nucleotide changes, and how some of these characteristics are inherited from one generation to another. It is mainly a study of how changes to the chromatin structure effects phenotypic changes in an organism without any changes in the genotype of the organism. Studies in social animals are now indicating how these chromatin changes induces behavioral changes in the organism with regards to pecking order, social assignments, mating, etc. .This essay is about how epigenetics changes influence social behavior of animals and humans.
Introduction
Epigenetics is the study of how gene expression or phenotypic changes happen in an organism, and how those changes are a result of mechanisms not related to changes in the actual DNA sequence of the organism.[1] Instead of molecular biological changes arising endogenously as a result of nucleotide substitution, in the case of epigenetics the changes are exogenic. These epigenetic changes are usually derived from the environment(prenatal and postnatal), and studies have been done showing the effect of epigenetics changes on the social behavior of animals and humans. Extensive studies exploring the various mechanisms and effects of epigenetics produce results that are directly challenging to the tenets of both Mendelian hereditary laws and Darwinian evolutionary theories, two of the most cherished dogmas in biological sciences. The mechanism by which epigenetics takes place comprises of many different methods, such as genomic imprinting, transvection, paramutation, gene silencing, heterochromatin and histone modifications, and epigenetic bookmarking. [2]
Discussion
Genomic imprinting is an inheritance process where the parental genetic material are expressed in the offspring in a manner that is exclusively specific to each parent’s allele.[3] Imprinted genes are either expressed only from the father’s allele or the mother allele’s, not both. This goes against the classical Mendelian view of genetics which stated that the genes for a specific trait has to be passed down to an offspring from both parents. Genomic imprinting is a result of different methylation patterns of paternal and maternal alleles, thus leadings to different gene expression levels.[3,4] Another process by which epigenetic modification takes place is called paramutation, an event that occurs on single locus; paramutation happens when two alleles on a single locus interact with each other, thus resulting in one allele influencing the behavior of the other allele.[5] This also goes against classical Mendelian genetics, specifically the law of allelic segregation which states that when gametes are produced, alleles separate with one allele going to each gamete, and alleles do not influence each other.[5] As more research are being done exploring epigenetics, the more our knowledge of evolution and hereditary expands beyond previously accepted dogmas in biology.
Another epigenetic phenomenon is called gene silencing, a process used to regulate gene expression. Epigenetic gene silencing can be achieved either by post-translational modification or by post-transcriptional regulation. Post-translational modification entails the alteration of histone elements through such process as methylation, acetylation, ubiquitination, SUMOylation, citrullination, ADP-ribosylation, and deimination, these serves to control the states of the chromatin complex, thereby regulating gene expression. [6] The other type of epigenetic gene silencing is post-translational modification, which is done with use of RNAi, that is, a complementary, secondary RNA is generated which then attaches itself to a primary RNA, thereby preventing the primary RNA from being translated due to enzymatic degradation.[7] RNAi stands for RNA interference. Gene silencing is not the only way that gene expression are regulated epigenetically, epigenetic transvection is another form. Epigenetic transvection is a form of gene regulation through the process of an allelic interaction; an allele on one chromosome interacts with another allele on a homologous chromosome to either activate or repress genetic activity.[8] This also goes against the Mendelian classical genetics of allele non-interaction. Epigenetic bookmarking is the process of cell memory where information from the parent’s gene expressions are transferred to the offspring, this helps ensure phenotypic fidelity of mitotic daughter cells.[9] For example, lung cells “knows and remember” to divide into lung cells and not some other type of cells.
Out of all the various types of epigenetic processes discussed, gene silencing through histones’ modification and chromatin modeling is one of the most studied. Chromatins are DNA bundled with histone proteins. In a tightly bundled state, DNA is inaccessible to various enzymes and proteins, including the polymerase. The way DNA is bundled around histone proteins depend on the shape and biochemical modifications of the coupling histone proteins.[10,11,12] These biochemical changes to the histone proteins are initiated by enzymes such as histone acetyltransferase or histone methyltransferase, for example. These type of enzymes operate through processes like methylation, acetylation, ubiquitination, ADP-ribosylation or phosphorylation of the histone’s N-terminal tail, resulting in biophysical changes in the histone proteins as part of the histone code hypothesis. Histone code hypothesis states that the regulation of DNA transcription is partly achieved through histone biochemical modification.[10,12] These biophysical changes affect the interaction of the histone proteins with the DNA, which in turn regulates the accessibility of the DNA to various cellular proteins and enzymes, thusly controlling gene expression. Also, these modified histones can act as a template for other histones, essentially, modified histones passing on their modification to other histones from one generation of cells to another[10].
The histone acetyltransferase process of chromatin modification is the most studied out of the histone transferase processes; the methodology of histone unbinding from the DNA occurs when the negatively charged DNA loosens itself from the positively charged histone N-terminal due to histone acetyltransferase enzyme rendering the positively charged histone N-terminal into a neutral amide linkage. These modifications can be hereditary[11,12]. The other model of epigenetic chromatin modification through histone occurs after the histone N-terminal tails undergoes modification by various histone transferase enzymes, it then becomes a docking site for other enzymes that modifies the chromatin structure.[12] Likewise, these modifications are sometimes hereditary from one generation to another. The direct methylation of the DNA itself occur through the process of converting cytosine into methylcytosine, usually at the CpG sites, which are regions on the DNA where cytosine nucleotide appears next to a guanine in a repeating manner, hence the CpG acronym.[13] The hypothesis of the histone code combined with DNA methylation forms the basis of the epigenetic code hypothesis. Epigenetic code hypothesis states that DNA methylation and histone modifications regulates epigenetic activity of cells and tissues. [14] Some of these CpG sites can be heavily methylated which can results in the low transcriptional frequency than other areas. Also, these methylation patterns can be transmitted from parent cells to daughter cells[13].
All these biochemical process of epigenetic control of gene expression discussed above plays a lot of roles in an organism behavior. Epigenetic studies into how gene regulation affect social behavior turns out interesting results, giving us another window into understanding how and why social organism interact associates each other in a certain manner. It brings a molecular genetics approach into a domain usually dominated by sociology, psychology and cultural anthropology. While the underlying DNA sequence remains unchanged, environmental(prenatal or postnatal) can affect gene expression levels, RNA transcript, chromatin structure, and DNA methylation which in turns affect social behavior. For example, a queen honey bee, Apis mellifera, have the same genetic makeup as her worker bees, while the queen bee is fertile and can live for several years, her worker bees on the other hand are infertile and can only live a couple of weeks.[15] Despite the fact that the queen and the worker bees have the same genetic makeup, the social standing and social behavior of the queen and the worker bees are very different. The gene expression pattern of the queen in comparison to the worker bees are different; even the functional physiology of the queen and the worker bees are different: the queen is fertile and the worker bees are sterile, despite having exact genetic makeup. Epigenetics studies of Apis mellifera solved this riddle. The factor responsible for these physiological and social differences is diet. Studies on bee’s behavior and dietary habits found out that randomly selected young baby bees that are fed a continuous diet of royal jelly will in all likelihood grow up to be queen; and the rest of baby bees that were not fed a continuous diet of royal jelly will be sterile and only live for a couple of weeks.[15] The royal jelly, when consumed by the baby bees induces methylation of the gene sequence that codes for DNA methyltranferase(DNMT3), essentially inactivating it[15]. It was experimentally determined that when DNMT3 is gene silenced in bee larvae, most of the larvae turn into queens; but when DNMT3 is optimally active in bee larvae most of the larvae turn into worker bees. The researchers noted similarity in gene expression pattern when they then looked at the gene expression patterns of bees been fed royal jelly compared to bees with suppressed DNMT3. They then concluded that eating royal jelly and DNA methylation both serves the same purpose of controlling gene expression. This is an example of how diet has an epigenetic effect on gene regulation in an organism, which in turn determine the social hierarchy of an organism in a society, essentially, epigenetics influencing social behavior in an organism.
Population also have an epigenetic effect on bee’s social behaviors through pheromones. A worker bee’s life is generally divided into two stages, first is a maturation stage of 2 to 3 weeks of non-foraging behavior where young bees maintain the hive and the brood. This stage is then followed by a 4 to 6 weeks stage when the bees forage for food for the remainder of their short lives. Essentially, worker bees’ life can be classified into two stages: younger hive bees and older foraging bees.[16] They discovered that when there is a sudden, massive population decrease among the class of older forager bees, younger hive bees will mature physically at a prodigious rate , rapidly turning from hive bees into forager bees well before the maturation time of 2 to 3 weeks. Essentially, filling the gap left by sudden shortage of older forager bees. Is there a biochemical angle to this sudden change in social assignment/behavior? The answer is the epigenetics effects of pheromones. The sudden, massive decrease in foraging bees, as a consequence, decreases the suppressing pheromones released by forager bees. [16]These suppressing pheromones work to inactivate the transcription of the foraging gene(the for gene) in younger hive bees. Once this epigenetic means of gene suppression is lowered due to population shortage of forager bees, the for genes transcription becomes very active, quickly turning hives bees into forager bees in short amount of time. The researchers analyzed gene expression patterns in brains of hive bees in comparison to the brains of forager bees. The result shows that forager bees have a much higher expression level of the foraging protein known as for in contrast to the lower levels in the brains of hive bees.[17] When younger hive bees were pharmaceutically treated with for, their social behavior changed very quickly from hive bees to forager bees, indicating the epigenetic nature of task assignment, social behavior and hierarchy in bees.[17]
Honey bees are not the only organism with these social characteristics, studies have been done on songbirds like zebra finch birds. These studies confirmed that songs have an epigenetic effect, this is indicated by the fact that different expression levels of egr-1 proteins are generated in response to different kinds of songs. Egr-1 is called early growth protein-1 and plays roles in neuronal plasticity; egr-1 protein is also active in the auditory forebrain of songbirds as a transcriptional factor. [18] Egr-1 expression level goes up within minutes when songbirds are exposed to songs that they are not familiar with, the exception being white noises and pure tones. Meaning that the expression level of these egr-1 proteins depend on the familiarity of the song being produced by other songbirds, and familiarity is a function of social circle. A familiar song is a song frequently made by other songbirds in the same social circle thus explaining its familiarity. Unfamiliar songs are made by songbirds outside of social circle, or by predators. Essentially, the epigenetic expression pattern of egr-1 in auditory forebrain of songbirds is anchored to social familiarity, and social familiarity guides interaction among songbirds. This is another example of epigenetics influencing and guiding social behaviors of animals. Another striking example of epigenetics and social behavior is the production of egr-1 in cichlid fishes. Egr-1 production in cichlid fishes is a function of a cichlid fish position on the social ladder.[18] When an alpha male cichlid fish is absent in the vicinity of a collective of cichlid fishes, the next dominant male will start producing egr-1 in its hypothalamus neurons while exhibiting dominant behavior. This shows the role of epigenetics in the social behavior of emergent alpha male cichlid fishes. The study also shows that in cichlid fishes, egr-1 has a regulating effect on other genes expression depending on the social condition, adding weight to the strong interaction of epigenetics and social behavior in cichlid fishes. [19]
The social nature of epigenetics in humans are not as well studied as it is the case with other social animals, due to the ethical challenge of the need to obtain tissue samples for studies. However, some promising epigenetic results came from monitoring pregnant mothers with depression and the possible epigenetic effect of maternal mood on infant’s social behavior, such as ability to handle social stress. Studies on this shows that prenatal exposure to maternal depression in the third trimester was associated with elevated levels of GR 1F promoter DNA methylation in these women. [20] These increased levels of methylation were also associated to the changes in levels of cortisol found in the saliva of three months old infants of these mothers.[20] Another study found that there is a correlation between cortisol levels and isolation behavior in children, indicating a possible epigenetic connection between maternal mood and social behavior in children.[21]
Conclusion
All these examples of epigenetic regulation of organism challenges the Darwinian model of evolution that posits organismal changes are very slow and takes a long time to happen. [22]In these epigenetic cases listed in this essay, the changes starts from minutes to a few months, it doesn’t take eons for changes to take place as it does with Darwinian evolution. Another way that epigenetic challenges Darwinism is through the Darwinian concept of natural selection, that is, the conception that traits evolved randomly independent of the environment, that the only role the environment plays is selecting which traits will survive or not.[22] Simply, the environment only plays a role in trait selection but not in the traits origination. Epigenetics decisively counters this Darwinian evolutionary view point by clearly depicting the role that environment plays in generating or originating specific traits through the use of gene expression patterns; and how those traits subsequently influence social behavior. In epigenetics, traits are effected by the environment, unlike Darwinism where traits are affected by the environment. Traits are not just a random occurring events to be sieved out by the environment in which they occur. In a nutshell, epigenetics shift more towards Lamarckism than Darwinism.
Lamarckian theory of evolution states that traits arise because of the need in the environment for that trait, and those trait were then passed on to the next generation.[23,24] This is contrary to Darwinism that believes that traits just randomly evolve, and the ones that are dominant are the traits lucky enough to be most adaptive to a specific environment. Also, from a Darwinian point of view traits are much more static, an organism either has a trait, or it doesn’t. In epigenetics, traits are much more dynamic with the gene expression getting turned off or on, depending on whether the environmental factors have changed. Darwinism is not the only established biological tenets to be challenged by epigenetics; as pointed out earlier in the beginning of this essay, Mendelian classical genetics theory of allelic segregation and the theory of independent assortment are also challenged. Epigenetics mechanism of paramutation, transvection, genomic imprinting, and epigenetic bookmarking are contrarian to Mendelian classical genetics theories.
Epigenetics is a basically stating that genes are not destiny. And that some of the social behavior of animals and humans can be explained from understanding the epigenetic role of environmental factors. Knowing that environmental stressors alter genetic expression and those genetic expression pattern can be inherited and exhibited in social behavior long after those environmental stressors have been eliminated is a watershed event. It is no longer an issue of nature versus nurture, it is both. Mental illness, anti-social behavior, human mate selection, social games and interaction, social pecking order, dietary habit all shows promise of having epigenetics study shed new lights into them in a manner that goes beyond psychology, sociology or anthropology.
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