Barriers of Polygenic Metabolic Engineering Luigi Leung 80171899 D105 – Fall 2007
As of today, almost all* GMOs on the market contain only one modification (monogenic change) in the original hosts’ genome: turn on an “off” gene in the host knock out an existing gene inserting a new foreign gene *polygenic: Golden Rice is not on market; it contains 2 modifications. Golden Rice 2 is not on market yet; it also contains 2 modifications. Orange GloFish contains 2 modifications (but banned for sale in California since Jan 2007).
The limit to monogenetic changes results in the inability to meet the many Gene Food promises ( all at the same time ) that many people have expected or hoped: Increase nutritional value Better tasting / more flavorful foods Increase crop yield More efficient uptake of resources  (waste less = less pollution)
Nothing can be accomplished until scientists have: - identified the relevant genes - figured out what they do - figured out how the proteins work in the organism Time Cost
The process of gene transfer could put the new gene anywhere randomly in the genome, possibly messing up other genes. Desired insertion in the correct position will take time and some trial and error. (Time & Cost) Products with non-desired changes are discarded. (Cost)
Genomes change naturally Cross over chromosomal exchanges generate genetic variation that might affect  inserted gene Transposons jumping genes might jump into and disrupt the inserted gene Mutations Viruses
Cross over can happen within the transferred gene (transgene)
Because of the reasons mentioned, the success of getting the desired result decreases exponentially as more and more genes are modified.
Modify more than one genes that have similar effects to control one trait. For example: enzymeA increases the synthesis of nutrientA enzymeB increases the synthesis of nutrientA Activate/insert genes for both enzA and enzB (this increases the likelihood of the nutrientA synthesis) Patience
Golden Rice β -carotene producing rice (vitamin A) 2 genes inserted phytoene synthase (psy) - from daffodil [Golden Rice] - from maize [Golden Rice 2; 23x more vitamin A] phytoene desaturase (crt I) - from soil bacterium,  Erwinia uredovora
(above)  Increased golden yellow color shows increased amount of  β- carotene. (side)  The bottleneck in the metabolic pathway of Golden Rice 1 is the PSY activity (first top line on the diagram). By using PSY gene from maize instead, the synthesis of  β- carotene increased 23 times.
Polygenic metabolic engineering is the beginning of another biotechnology breakthrough. When we are not limited to only single changes in an organism’s genome, the ability to meet the many Gene Food promises becomes increasingly possible.
Rader, Charles. “A Report on Genetically Engineered Crops.” April 2006. 3 Nov 2007. <http://members.tripod.com/c_rader0/gemod.htm> Yorktown Technologies. “Fluorescent Transgenic Zebrafish.” GloFish. 2007. 3 Nov 2007.  <http://www.glofish.com/development.image.htm> Golden Rice Humanitarian Board. “The science behind Golden Rice.” Golden Rice. 2007. 3 Nov 2007. <http://www.goldenrice.org/Content2-How/how1_sci.html> Masipag. “Grains of delusion: Golden rice seen from the ground” February 2001. 3 Nov 2007.  <http://www.grain.org/briefings/?id=18> “ Golden rice.” Wikipedia, The Free Encyclopedia. 2 Nov 2007, 09:36 UTC. Wikimedia Foundation, Inc. 2 Nov 2007. <http://en.wikipedia.org/w/index.php?title=Golden_rice&oldid=169344619>.  “ The Nobel Prize in Physiology or Medicine 2007: Gene modification in mice” Oct 2007. Nobel Web. 4 Nov 2007. <http://nobelprize.org/nobel_prizes/medicine/laureates/2007/adv.html>

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Barriers Of Polygenic Metabolic Engineering

  • 1. Barriers of Polygenic Metabolic Engineering Luigi Leung 80171899 D105 – Fall 2007
  • 2. As of today, almost all* GMOs on the market contain only one modification (monogenic change) in the original hosts’ genome: turn on an “off” gene in the host knock out an existing gene inserting a new foreign gene *polygenic: Golden Rice is not on market; it contains 2 modifications. Golden Rice 2 is not on market yet; it also contains 2 modifications. Orange GloFish contains 2 modifications (but banned for sale in California since Jan 2007).
  • 3. The limit to monogenetic changes results in the inability to meet the many Gene Food promises ( all at the same time ) that many people have expected or hoped: Increase nutritional value Better tasting / more flavorful foods Increase crop yield More efficient uptake of resources (waste less = less pollution)
  • 4. Nothing can be accomplished until scientists have: - identified the relevant genes - figured out what they do - figured out how the proteins work in the organism Time Cost
  • 5. The process of gene transfer could put the new gene anywhere randomly in the genome, possibly messing up other genes. Desired insertion in the correct position will take time and some trial and error. (Time & Cost) Products with non-desired changes are discarded. (Cost)
  • 6. Genomes change naturally Cross over chromosomal exchanges generate genetic variation that might affect inserted gene Transposons jumping genes might jump into and disrupt the inserted gene Mutations Viruses
  • 7. Cross over can happen within the transferred gene (transgene)
  • 8. Because of the reasons mentioned, the success of getting the desired result decreases exponentially as more and more genes are modified.
  • 9. Modify more than one genes that have similar effects to control one trait. For example: enzymeA increases the synthesis of nutrientA enzymeB increases the synthesis of nutrientA Activate/insert genes for both enzA and enzB (this increases the likelihood of the nutrientA synthesis) Patience
  • 10. Golden Rice β -carotene producing rice (vitamin A) 2 genes inserted phytoene synthase (psy) - from daffodil [Golden Rice] - from maize [Golden Rice 2; 23x more vitamin A] phytoene desaturase (crt I) - from soil bacterium, Erwinia uredovora
  • 11. (above) Increased golden yellow color shows increased amount of β- carotene. (side) The bottleneck in the metabolic pathway of Golden Rice 1 is the PSY activity (first top line on the diagram). By using PSY gene from maize instead, the synthesis of β- carotene increased 23 times.
  • 12. Polygenic metabolic engineering is the beginning of another biotechnology breakthrough. When we are not limited to only single changes in an organism’s genome, the ability to meet the many Gene Food promises becomes increasingly possible.
  • 13. Rader, Charles. “A Report on Genetically Engineered Crops.” April 2006. 3 Nov 2007. <http://members.tripod.com/c_rader0/gemod.htm> Yorktown Technologies. “Fluorescent Transgenic Zebrafish.” GloFish. 2007. 3 Nov 2007. <http://www.glofish.com/development.image.htm> Golden Rice Humanitarian Board. “The science behind Golden Rice.” Golden Rice. 2007. 3 Nov 2007. <http://www.goldenrice.org/Content2-How/how1_sci.html> Masipag. “Grains of delusion: Golden rice seen from the ground” February 2001. 3 Nov 2007. <http://www.grain.org/briefings/?id=18> “ Golden rice.” Wikipedia, The Free Encyclopedia. 2 Nov 2007, 09:36 UTC. Wikimedia Foundation, Inc. 2 Nov 2007. <http://en.wikipedia.org/w/index.php?title=Golden_rice&oldid=169344619>. “ The Nobel Prize in Physiology or Medicine 2007: Gene modification in mice” Oct 2007. Nobel Web. 4 Nov 2007. <http://nobelprize.org/nobel_prizes/medicine/laureates/2007/adv.html>