 I'd like to read today from a paper, a letter really, published in 1972 in the Brookhaven Symposia on Biology. The author is Dr. Susumu Ono, one of the great molecular geneticists of the modern era. Susumu was born to Japanese parents in Korea, but spent most of his life in the US. He had a lifelong love of horses, leading him to get a DVM, that's a doctor of veterinary medicine, and then an additional PhD and doctor of science a few years later. He is what I call a triple doctor. His work concerned the role of chromosomal exchange, and particularly on these sex chromosomes. He spent 40 years in research at City of Hope, a very important research hospital in Los Angeles. He is famous for uncovering the nature of the bar body, the ex-chromosome that is inactivated in females, indicated in the graph as Big X Little I. The inactivation is random in each cell during development, leading to unusual mosaicism like the female calico cat. His work led to what is known as Ono's law, which states that a gene X-linked in one mammal species will be X-linked in all mammal species. This has been an important discovery in modern genetic disease studies. We sometimes find exceptions to the law, such as monotremes, but it has held up remarkably well. He also explored the role of gene duplication and drift in creating new genetic information and evolution. His most controversial work, and it says something that we are still debating it, is called the 2R Hypothesis, or Ono's Hypothesis. It states that at some point in the distant lineage of modern organisms, duplications of entire genomes called polyploidizations occurred and resulted in large jumps in genetic information. These duplicated chromosomes contain thousands of genes, and once duplicated, they became less constrained by natural selection. This allowed for a phenomenon called neo-functionalization, which just means that they were allowed to mutate a bit more and result in new phenotypes. We can see the evidence for these paleopolyploidies by looking at very closely related genes within a single genome. By back-calculating drift rates, we see that many gene families emerged all at once, suggesting that some single event produced copies of whole chromosomes or whole genomes. This also helps to explain why some organisms, like the pufferfish and salamander, have so much DNA but so few genes. This idea is called the C-value paradox. The C-value was the number of DNA bases an organism has. It turns out not to correlate with how many genes are in that genome. So Sumo in the paper I'm about to read excerpts from framed this paradox as the question of the non-coding DNA, which he playfully calls junk DNA. Listen carefully and see if you think he dismisses that as unimportant or uninteresting, as the Discovery Institute would have you think. The mammalian genome, haploid chromosome complement, contains roughly 3 times 10 to the minus 9th milligrams of DNA, which represents 3 times 10 to the 9th base pairs. This is at least 750 times the genome size of E. coli. If we take the simplistic assumption that the number of genes contained is proportional to the genome size, we would have to conclude that 3 million or so genes are contained in our genome. The falseness of such an assumption becomes clear when we realize that the genome of lowly lung fish and salamanders can be 36 times greater than our own. In fact, there seems to be a strict upper limit for the number of gene loci which we can afford to keep in our genome. Consequently, only a fraction of our DNA appears to function as genes. The observations on a number of structural gene loci of man, mice, and other organisms revealed that each locus has a 10 to the minus 5th per generation probability of sustaining a dilaterious mutation. It then follows that the moment we acquire 10 to the 5th gene loci, the overall dilaterious mutation rate per generation becomes 1, which appears to represent an unbearably heavy genetic load. Taking into consideration the fact that dilaterious mutations can be dominant or recessive, the total number of gene loci of man has been estimated to be about 3 times 10 to the 4th. More than 90% degeneracy contained within our genome should be kept in mind when we consider evolution changes in genome sizes. What is the reason behind this degeneracy? Certain untranscribable and or untranslatable DNA-based sequences appear to be useful in a negative way, the importance of doing nothing. It may be of selective advantage to space adjacent genes far enough apart by inserting a stretch of untranscribable and or untranslatable DNA-based sequence as a partition. In this way the dilaterious effects of nonsense or frameshift mutations can be confined to a single locus, instead of allowing it to spread to other genes. Our view is that these partitioning sequences are the remains of nature's experiments which failed. The Earth is strewn with fossil remains of extinct species. Is it a wonder that our genome too is filled with the remains of extinct genes? It then follows that the creation of a new gene with hitherto non-existent function is possible only if a gene becomes sheltered from relentless pressure of natural selection. This shelter has apparently been provided either by polyplotization or by tandem duplication. Redundant copies of genes thus produced are now free to accumulate formerly forbidden mutations and thereby to acquire new functions. The chance of acquiring a new function by unrestricted accumulation of mutations, however, should be as small as that of an isolated population emerging triumphant as a new species. Degeneracy is the more likely fate. The creation of every new gene must have been accompanied by many other redundant copies joining the ranks of silent DNA-based sequences. And these silent DNA-based sequences may now be serving the useful but negative function of spacing those who have succeeded. Triumphs as well as failures of nature's past experiments appear to be contained in our genome.