Welcome to the Genome. Michael Yudell

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Welcome to the Genome - Michael Yudell


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ratios 3:1 and 9:3:3:1. Either way, his conclusions have not been overturned.

      Mendel died on January 6, 1884, nearly 20 years after his momentous study with Pisum had been published. (26) Even though its significance remained unheralded, Mendel’s work as a scientist and as a servant of God was recognized by his peers. If Mendel had been luckier in choosing the journal in which to publish his findings, he might have been famous in his own time, but he published in an obscure scientific journal and died in genetic obscurity (his monastic calling guaranteed that). (27) Although his contemporaries did cite his work with Pisum, they probably did not comprehend its deeper meanings for what would become a cornerstone of hereditary theory. A tribute to Mendel by a fellow scientist in Brünn lauded him as one of the great scientists of his day who worked “almost exclusively on detailed natural scientific studies, in which he displayed a totally independent, unique way of thinking.” (28) Unfortunately, it would take the world another 16 years after his death to uncover the greatness of Mendel’s investigations.

      The lack of attention to Mendel’s work may also be explained by the near obsession with evolution in the mid‐nineteenth century after the publication of Darwin’s The Origin of Species. Darwin’s work was published just 6 years before Mendel’s and captured public attention well into the twentieth century, leaving Mendel’s theory to languish quietly. (29)

      The “rediscovery” of Mendel in 1900 was driven in part by what biologist Ernst Mayr calls “an accelerating interest in the problem of inheritance.” (30) Incredibly, in the spring of that year three botanists—Hugo de Vries, Carl Correns, and Erich Tschermak—all claimed to have discovered laws of inheritance. They soon learned, unfortunately, that Mendel’s work was nearly identical and had preceded them by 35 years. (31) In the coming decades, Mendel’s laws of segregation and independent assortment would be tested on a wide variety of species.

      With only four pairs of chromosomes, the ability to produce offspring at a pace that would make even the most reproductively prolific blush, and the fact that it can live in the austere environment of a laboratory storage bottle, the six‐legged Drosophila melanogaster, or fruit fly, has been the workhorse of genetics for more than 100 years.

      Beginning early in the twentieth century, Thomas Hunt Morgan and his students at Columbia University capitalized on Drosophila’s valuable qualities and began breeding fruit flies by the hundreds of thousands, hoping to find variations or mutations in fruit fly traits that would help explain Mendel’s laws in real‐life situations. Morgan’s laboratory, dominated by work with Drosophila, became known as the fly room, a moniker that can only partly suggest the overwhelming number of flies present in a space that measured just 16 × 23 feet. (32) Today the fly room is frequented by one of the present authors—part of it still exists at Columbia University (if you are looking for it, it is now the men’s bathroom on the sixth floor of Schermerhorn Hall).

      During the 1910s, thanks in large part to the work conducted in the fly room, genetics shifted from simply testing Mendel’s laws of inheritance to studying the physical arrangement of genes on chromosomes. Interestingly enough, the terminology of what we now call genetics was not even in place. Morgan and his genetically minded colleagues were pioneers in a field that was quickly becoming known as genetics, a word coined by botanist William Bateson in 1906. The word gene was itself first defined by the German biologist Wilhelm Johannsen in 1909. (33) The new terminology and the field of work and entity it describes are still used today.

      Morgan, formerly a critic of Mendelian theory, came to embrace the new genetics because of some surprising results in his own research. In 1910 he discovered something startling among one of his breeds of Drosophila—a lone white‐eyed male fly. When it was bred with a normal (red‐eyed) female, all of the offspring had red eyes. When flies from the first generation were crossed, the white‐eyed character reappeared, but surprisingly only in half of the males. Finally, when white‐eyed males were bred with first‐generation females, 50% of both males and females had white eyes. Morgan called this change a mutation and spent much of his career studying such mutations in order to decipher the nature of genes and the structure of chromosomes. (34)

      Ultimately Morgan saw that Mendelian laws of segregation and independent assortment easily explained these patterns. Morgan’s biographer Garland Allen suggests that these results were the main factor in Morgan’s acceptance of Mendelism. (35)

Image described by caption.

       Credit: Daniel Marenda, PhD and the Marenda Laboratory

      The cause of a mutation can be the result of exposure to radiation, but as was the case in the Morgan lab, the causes of mutations for a white‐eyed variation were probably far more ordinary. The white‐eyed trait most likely arose from a random error in the DNA replication process. Less likely, the mutation may have been caused by a mutagen, an agent that can cause mutation. Temperature changes during gestation, environmental exposures, certain viruses, radiation, ultraviolet light, and chemicals can all act as mutagens. By using the mutations found in Drosophila, Morgan was able to begin to map the Drosophila genome. (38) This was not like the modern genome sequence maps that we hear a lot about


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