Week 2

Homework Questions & Answers

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?
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?

DNA polymerase has an intrinsic error rate of approximately 1 mistake per 10⁶ nucleotides incorporated. Given that the human genome is roughly 3 × 10⁹ base pairs long, this would result in thousands of errors per replication cycle in the absence of correction mechanisms. Biology addresses this discrepancy through the proofreading activity of DNA polymerase and post-replicative mismatch repair systems, which dramatically reduce the final mutation rate.
Due to the degeneracy of the genetic code, there exists an astronomically large number of DNA sequences capable of encoding an average human protein. However, in practice, not all of these sequences are equally viable. Factors such as mRNA stability, codon usage bias, translational efficiency, secondary structure formation, and regulatory sequence constraints limit the set of functional coding sequences.

The most commonly used method for oligonucleotide synthesis is solid-phase chemical synthesis using phosphoramidite chemistry.
It is difficult to synthesize oligonucleotides longer than ~200 nucleotides because the coupling efficiency at each synthesis cycle is not perfect, leading to the progressive accumulation of errors and truncated products as the length increases.
A 2000 bp gene cannot be synthesized directly because the cumulative error rate and product truncation become overwhelmingly high, preventing the recovery of a correct full-length sequence in sufficient yield and purity.

What are the 10 essential amino acids in all animals, and how does this affect your view of the “Lysine Contingency”?

The ten essential amino acids in animals are: