Week 1 HW: Slide Responses

Professor Jacobson:

  1. The error rate for polymerase is 1:10^6. Compared to the length of the human genome of around 3.2Gbp (slide 10), the error rate is minute, occurring perhaps once in one genome. Biology deals with this discrepancy by proofreading the action before it is coded into the DNA.
  2. There are 20 AA and 61 codons that specify amino acids (NHGRI), leading to different ways to code for an average human protein. Some reasons that all of these different codes don’t work for the protein of interest could be due to the physical structure of the protein, and the efficiency of each pathway. (not totally sure of this answer)

Dr.Leproust

  1. The most common method for oligo synthesis is currently a chip based gene synthesis that couples the nucleotide with phosphonamidite. Historically, this has been a solid phase synthesis.
  2. It’s difficult to make oligos longer than 200nt vir direct synthesis because of the surface and primarily the inefficiency of the current state of the art phosphonamidite method. Source: Yin Y, Arneson R, Yuan Y, Fang S. Long oligos: direct chemical synthesis of genes with up to 1728 nucleotides. Chem Sci. 2024 Dec 18;16(4):1966-1973. doi: 10.1039/d4sc06958g. PMID: 39759933; PMCID: PMC11694485.
  3. You can’t make a 2000bp gene with direct olio synthesis because of the increased error rate in PCR. The new gene pool solution offers a 1 in 3,000 bp error rate which would allow for greater gene lengths to be processed. (slide 39)

Professor George Church

  1. According to the NIH, the nine essential amino acids are histidine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. This means that the Lysine Contingency is really already a contingency that all animals have upon receiving all nine of these AAs from their diet, not just lysine. (Fictional) dinosaurs are just like you and me, minus 8 more essential amino acids. Source: Lopez MJ, Mohiuddin SS. Biochemistry, Essential Amino Acids. Updated 2024 Apr 30. In: StatPearls Internet. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557845/