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The discovery of nested genes: More than meets the fly

OTHER VIDEOS YOU MIGHT LIKE: • Recoding genomes: The hip new trend in synthetic biology -    • Recoding genomes: The hip new trend i...   • Discovering mutagenic DNA polymerase IV in E. coli -    • Discovering mutagenic DNA polymerase ...   • Gene duplication: The formation of new genes… genes… genes -    • Gene duplication: The formation of ne...   You know those pesky little fruit flies you just can’t seem to get out of your kitchen? Believe or not, they are some of the most important eukaryotes in the world. Why? Genetics. In the early 20th century, Thomas Hunt Morgan used Drosophila to uncover the fundamental organisation of the genome, forming the ‘Beads on a String’ theory to describe genes as discrete units. Later, in 1941, Beadle and Tatum would visit our other favourite kitchen friend, the fungus, and expand Morgan’s work to conceive the ‘One Gene – One Enzyme’ hypothesis. Now that we understood the relationship between genes and biochemical pathways, the complexities of genome organisation continued to unfold. In 1986, a team of four geneticists made a revolutionary discovery in Drosophila melanogaster with the discovery of “nested genes”. They Mapped the Gart locus, a region on Drosophila chromosome 2L, locus 24D, known to encode three enzymatic functions in purine biosynthesis, making it an essential housekeeping gene for organism function. Computer analysis then revealed something bizarre. An open reading frame on the non-coding strand, opposite the first intron in the purine biosynthesis gene. Analysis showed this gene to encode a protein for pupal cuticle synthesis, a developmental gene transcribed for just three hours in the flies’ entire lifespan. It was an incredible discovery, and further investigation found undeniable similarities between the intronic gene and other pupal cuticle genes in the Drosophila melanogaster genome, as well as the same arrangement in a related Drosophila species. Was it transposition in Drosophila’s evolutionary history that caused this? Who knows… but what we do know is that this arrangement is not uncommon, and there’s at least 150 of them in you! With the recent additional discovery of non-intronic nested genes, it is clear that understanding this type of arrangement is a crucial piece in the puzzle that is the genetic code. Creator: Ashlee Rodd References: Sex limited inheritance in Drosophila. Morgan, Thomas H. Sex limited inheritance in Drosophila. Science. 1910 Jul 32(812), 120-122 doi: 10.1126/science.32.812.120. Genetic control of biochemical reactions in Neurospora. Beadle GW, Tatum EL. Proc Natl Acad Sci U S A. 1941 Nov 15;27(11):499-506. doi: 10.1073/pnas.27.11.499. Gene within a gene: nested Drosophila genes encode unrelated proteins on opposite DNA strands. Henikoff S, Keene MA, Fechtel K, Fristrom JW. Cell. 1986 Jan 17;44(1):33-42. doi: 10.1016/0092-8674(86)90482-4. Multiple purine pathway enzyme activities are encoded at a single genetic locus in Drosophila. Henikoff, S., Keene, M. A., Sloan, J. S., Balkan, J., Hards, R., & Patterson, D. Proceedings of the National Academy of Sciences of the United States of America. 1986 Feb 83(3), 720–724. doi: 10.1073/pnas.83.3.720. Conserved arrangement of nested genes at the Drosophila Gart locus. Henikoff, S., & Eghtedarzadeh, M. K. Genetics. 1987 Dec 117(4), 711–725. doi: 10.1093/genetics/117.4.711 Characterization and functional annotation of nested transposable elements in eukaryotic genomes. Gao, C., Xiao, M., Ren, X., Hayward, A., Yin, J., Wu, L., Fu, D., Li, J. Genomics. 2012 Oct 100(4), 222-230. doi: 10.1016/j.ygeno.2012.07.004. The evolution and functional significance of nested gene structures in Drosophila melanogaster. Lee, Y. C., & Chang, H. H. Genome biology and evolution. 2013 Oct 5(10), 1978–1985. doi: 10.1093/gbe/evt149 Unconventional genomic architecture in the budding yeast Saccharomyces cerevisiae masks the nested antisense gene NAG1. Ma, J., Dobry, C. J., Krysan, D. J., & Kumar, A. Eukaryotic cell. 2008 Feb 7(8), 1289–1298. doi: 10.1128/EC.00053-08 Nested genes in the human genome. Yu, P., Ma, D., & Xu, M. Genomics. 2005 Oct 86(4), 414–422. doi: 10.1016/j.ygeno.2005.06.008