Saturday, July 21, 2007

Darwin to Central Dogma: How We Get Protein from the Genetic Code. Part I

Once upon a time, a wise man said, "Timing is everything." A major difficulty of Darwin's theory of organic evolution by natural selection (1859), as revolutionary as it has been, resulted from the timing of his life and work. Don't get me wrong, Darwin's theory came at a crucial point in the development of modern science and was only made possible by the discoveries just preceding his work. But it was constrained by the ignorance and interests of the scientific community of its day.


Darwin constructed a theory that explained how natural environmental forces and interactions shaped the evolution of heritable traits in a non-random fashion, giving a mechanism responsible for the design and diversity found in the natural world. Based on systematics, geology, developmental embryology, biogeography, popluation studies and a host of other evidence, Darwin devised the unifying theory of biology, no bones about it. What he lacked, however, was a robust theory of how these traits were passed from one generation to the next. Enter: the biologists' favorite monk.


Gregor Mendel was a Moravian monk. His birthday was July 20, 1822. His alma mater was the University of Vienna. Mendel was a contemporary of Darwin's credited with conducting rigorous scientific inquiry into plant hybridization incorporating experimentation and statistics (probability theory). Mendel worked out two simple theories of inheritance that form the basis of modern genetics: (a) the theory of segregation and (b) the theory of independent assortment of alleles. Around 1865, Mendel published a few papers on his inheritance work. Mendel owned a copy of Darwin's Origin, and it is thought his writing reflects a Darwinian influence in some passages; conversely, Darwin was also familiar with Mendel's work although he did not possess copies of Mendel's few papers. Had not Mendel substituted activism and religious duties for his scientific research a short time after his publications, his findings might have been acknowledged. Instead, his work was never fully appreciated until after his death, when several scientists rediscovered and redistributed his papers and quickly developed a modern theory of inheritance based upon them.


Modern advances in statistical analyses and population genetics based on Mendelian inheritance theory were merged with Darwin's theory in the early 20th Century in what is now known as the "Modern Synthesis" of evolutionary thought. Key players in this synthesis included biostatisticians, early geneticists, population biologists such as Morgan, Mayr, Fisher, Wright, Simpson, Haldane, et cetera. As genetics developed, it became understood that variation in heritable traits were the result of genetic variation due to gene mutation at the chromosomal level, then the molecular level as DNA was established as semi-conservatively replicated genetic material by Hershey, Chase, Watson, Crick, Franklin, Meselson, Stahl, and others.


Meanwhile, since the 1930s, studies of biochemical metabolism and biosynthesis had been laying the foundation for uncovering what Francis Crick would later call the "Central Dogma of Molecular Biology." This discovery had its origins in a theory that single genes directed the synthesis of individual enzymes responsible for key biological functions as players in biochemical pathways. In the modern era, Crick and others empirically tested this hypothesis and revealed the answer to how phenotypes, in the form of proteins, arise from specific sequences of DNA, or genotypes. The Central Dogma states that DNA, sequences of nucleic acids, is transcribed into RNA, which is then translated into proteins, sequences of amino acids. These proteins may be enzymatic or non-enzymatic; regardless, they influence the function of living things from cellular to organismal levels.


But how does this happen? How does "biological information" get transferred?


Overview Figures:











DNA transcription


(in depth look at processes starts in Part 2)

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