After the rediscovery of Mendelism and, thereafter, the establishment ofehromosomc theory by Sutton and diovery in 1902, the pattern of heredity could be explained by the segregation of chromosomes during meiosis. Johansson coined the term gene for Mendel an factor in 1909. But, the question that kept the scientific community occupied for the next fifty years was about the exact connection between the hereditary traits and chromosomes.

During the same time, in 1902, Archibald Garrod, a British physician working with one of the early Mendel and geneticist, his countryman William Bateson made an interesting observation. Garrod observed that inherited disorder like alkaptonuria, where a patient produced black urine was due to the absence of an enzyme capable of breaking down homogentisic acid (alkapton) into simpler substances.

In the absence of this enzyme, the urine contains alkapton that is rapidly oxidized in air to turn black. Garrod observed that this disease was inherited in Mendel an pattern. This was the first pointer towards a relation between gene and enzyme.

Further, the nature of the genetic materials also came under investigations. Prior to the establishment of Mendelism, Mcischer discovered DXA in 1869, though he could not assign any role of DXA.

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With the advancement of molecular biology, it was established that chromosome chemically consisted of proteins and DXA. Gradually it became clear that protein consisted of twenty amino acids and DXA consisted of four nucleotides. Initially it appeared to the scientific community that proteins having a more varied and complex structures could be the possible genetic material.

The British microbiologist Frederick Griffth provided the first evidence for DXA as the genetic material.