Professor Hofstadter’s Hypothesis
According to Prof. Hofstadter the genetic code is as arbitrary as Gödel’s numbering scheme. He stated that one could surgically remove the anticodon from one end and the other end will not be affected by it or one can surgically remove the specially shaped Amino Acid tip of the tRNA and graft on an alien Amino Acid tip, which would then lure the wrong Amino Acid and make the tRNA embody a false piece of genetic code. He assumed that for each anticodon the tRNA that carried it would be shaped differently at its Amino Acid end. Later he explained that neither end of the tRNA knows anything about the other. He said that “Since the two ends of the tRNA are independent, the genetic code in principle be subverted and is therefore arbitrary.”
He also stated that the moment we insert the altered DNA into the cell many RNA polymerases will start working on it. They will transcribe it into strands of RNA. At this point various synthetases encountering the fresh tRNA’s will force the amino acids onto them. Now a synthetase comes along and encounters a familiar seeming DHU loop. It sticks on the very same amino acid it would have stuck on
before. According to him the enzyme had been deceived in exactly the way we wished. It has even become an accomplice to our deviltry, because according to the old genetic code, the tRNA is carrying the wrong anticodon for that amino acid, but according to the new code, it is carrying the right one.
He concluded by stating that if a piece of “alien” DNA can be inserted into a cell, the cell will proceed to manufacture new deep decoding machinery (ribosomes and tRNA’s), and therewith to produce all the proteins coded for in the alien way in the alien DNA. These proteins will then imbue the cell with the same external character as it had before, when it was using the ordinary genetic code.
Failure of Hofstadter’s Hypothesis
First of all the article by Prof. Hofstadter was written in 1985. Very limited knowledge that was available at that time and Genomics has transformed quite a lot in these past 3 decades. For some time it has been actually known that the genetic code can vary from one organism to another but recently researchers at Yale and at the University of Western Ontario have shown that the picture is not quite as simple as we would like to believe.
Mutations, changes in the DNA sequence of a gene, occur spontaneously in nature. Since alleles are forms of genes, mutations by definition create new alleles. For example the wild-type eye color of the fruit fly Drosophila is red, but a mutant allele of a gene on the X chromosome produces white eyes.
Mutation rates vary substantially among taxa, and even among different parts of the genome in a single organism. Scientists have reported mutation rates as low as 1 mistake per 100 million (10-8) to 1 billion (10-9) nucleotides, mostly in bacteria, and as high as 1 mistake per 100 (10-2) to 1,000 (10-3) nucleotides, the latter in a group of error-prone polymerase genes in humans (Johnson et al., 2000).
Even mutation rates as low as 10-10 can accumulate quickly over time, particularly in rapidly reproducing organisms like bacteria. This is one reason why antibiotic resistance is such an important public health problem; after all, mutations that accumulate in a population of bacteria provide ample genetic variation with which to adapt (or respond) to the natural selection pressures imposed by antibacterial drugs (Smolinski et al., 2003). Take E. coli, for example. The genome of this common intestinal bacterium has about 4.2 million base pairs, or 8.4 million bases. Assuming a mutation rate of 10-9(i.e., midway between reported estimates of 10-8 and 10-10), every time E. coli divides, each daughter cell will have, on average, 0.0084 new mutations. Or, another way to think about it is like this: Approximately 1% of bacterial cells will contain a new mutation. That may not seem like much. However, because bacteria can divide as rapidly as twice per hour, a single bacterium can grow into a colony of 1 million cells in only about 10 hours (220 = 1,048,576). At that point, approximately 10,000 of these bacteria will have accumulated at least one mutation. As the number of bacteria carrying different mutations increases, so too does the likelihood that at least one of them will develop a drug-resistant phenotype.
Likewise, in eukaryotes, cells accumulate mutations as they divide. In humans, if enough somatic mutations (i.e., mutations in body cells rather than sperm or egg cells) accumulate over the course of a person’s lifetime, the end result could be cancer. Or, less frequently, some cancer mutations are inherited from one or both parents; these are often referred to as germ-line mutations. One of the first cancer-associated somatic mutations was discovered in 1982, when researchers found that a mutated HRAS gene was associated with bladder cancer (Reddy et al., 1982). HRAS encodes for a protein that helps regulate cell division. Since then, scientists have identified several hundred additional “cancer genes.” Some of them, like the handful of germ-line mutations associated with a form of colorectal cancer known as hereditary nonpolyposis colorectal cancer (HNPCC), play crucial roles in DNA repair (Wijnen et al., 1998).
Of course, not all mutations are “bad.” But, because so many mutations can cause cancer, DNA repair is obviously a crucially important property of eukaryotic cells. However, too much of a good thing can be dangerous. If DNA repair were perfect and no mutations ever accumulated, there would be no genetic variation—and this variation serves as the raw material for evolution. Successful organisms have thus evolved the means to repair their DNA efficiently but not too efficiently, leaving just enough genetic variability for evolution to continue.
One small variation in a person’s genetic code can be the difference between a drug helping treat a disease—or causing a severe and possibly fatal reaction. Non-coding mutations in a gene can alter the gene’s function in many different ways.