Week 1 HW: Principles and Practices

Homework Questions from Professor Jacobson:

1.Nature’s machinery for copying DNA is called polymerase. What is the error rate of polymerase? How does this compare to the length of the human genome. How does biology deal with that discrepancy?

-DNA polymerase has an error rate of aprox one mistake per 10^{8 nucleotides during DNA replication. This significant on the human genome which has around 3 x10}9 base pairs, so without correction, this woul result in a lot of mutations per replication. Biology addresses this discrepancy through multiple error correction mechanisms, such as post replication mismatch repair, to reduce the error rate to aprox one error per 10^9 nucleotides, maintaining th genomic stability.

2.How many different ways are there to code (DNA nucleotide code) for an average human protein? In practice what are some of the reasons that all of these different codes don’t work to code for the protein of interest?

-Because the genetic code is degenerate, an average human protein of aprox 300 aminoacids can be encoded by a bunch of different DNA sequences creating a lot of different combinations, However, most of them do not function effectively. Factors such as codon bias, mRNA secondary strc, trasnlation spee, etc. limit which DNA sequences can successfully produce the desired protein. So, as a resultm only a small part of them are biologically viable.

Homework Questions from Dr. LeProust:

What’s the most commonly used method for oligo synthesis currently?

-The most commonly used method for oligonucleotide synthesis is solid-phase phosphoramidite chemistry

Why is it difficult to make oligos longer than 200nt via direct synthesis?

-Mainly due to error accumulation

Why can’t you make a 2000bp gene via direct oligo synthesis?

-Because the cumulative error rate would be extremely high

Homework Question from George Church:

What are the 10 essential amino acids in all animals and how does this affect your view of the “Lysine Contingency”? -histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, and arginine -Due to the fact that animal do not produce Lysine, the abscence of it can function as a killer switch for engineered organisms. as a form of contingency