Week 2 Lecture Preparation

Professor Jacobson

Question 1

DNA polymerase is the enzyme responsible for copying DNA during cell division. It does not work perfectly and has an error rate of about one mistake per 10⁷ to 10⁹ nucleotides. When this is compared to the size of the human genome, which is around 3 billion base pairs, it means that errors could potentially happen every time DNA is replicated. Biology deals with this problem by using several layers of correction. DNA polymerase can proofread its own work and fix mistakes as replication happens. In addition, cells have DNA repair systems that detect and correct remaining errors. Because of these mechanisms, most mistakes are fixed before they can cause serious problems, allowing genetic information to remain stable.

Question 2

The genetic code is described as degenerate because most amino acids can be encoded by more than one codon. This means that a protein consisting of 100 amino acids could theoretically be encoded in an extremely large number of different DNA sequences, due to the many possible codon combinations for each amino acid. However, biology does not take advantage of all this degeneracy. In practice, organisms show strong codon preferences, often referred to as codon bias. This is because certain codons are translated more efficiently or accurately, depending on the availability of tRNAs and the cellular machinery. Using preferred codons helps reduce translation errors, improve efficiency, and maintain proper protein folding. As a result, biological systems favor reliability and efficiency over using all possible coding options.

Dr. LeProust

Question 1

The most common method used for oligonucleotide synthesis is phosphoramidite chemistry. In this approach, DNA is synthesized step by step by adding one nucleotide at a time to a growing chain that is attached to a solid support. This method is widely used because it is reliable, efficient, and well suited for producing short DNA sequences with high precision.

Question 2

One of the main limitations of current DNA synthesis methods is the accumulation of errors as the DNA sequence becomes longer. Since nucleotides are added step by step, small inefficiencies at each step can lead to deletions or incorrect bases in the final sequence. As a result, synthesizing long DNA sequences becomes more challenging and often requires additional purification and verification steps. These limitations also increase the cost and time needed for DNA synthesis.

Question 3

Future improvements in DNA synthesis may focus on increasing accuracy and enabling the synthesis of longer DNA sequences. One promising direction is the development of enzymatic DNA synthesis, which may reduce error rates compared to traditional chemical methods. In addition, automation and computational tools, including AI-based design and quality control, could help optimize synthesis processes and detect errors more efficiently. Together, these advances could make DNA synthesis faster, cheaper, and more reliable.

George Church

Cells as Computers and Logic

The idea of cells as computers suggests that biological systems can process information in ways similar to electronic computers. In synthetic biology, genes and regulatory elements can be designed to function like logic gates, allowing cells to respond to specific inputs and produce predictable outputs. For example, a cell might produce a certain protein only when multiple conditions are met. This concept is exciting because it opens possibilities for smarter therapies, environmental sensing, and more precise biological control systems. However, cells are living systems and are much more complex and unpredictable than electronic computers. Small changes in the environment or mutations could lead to unexpected behavior. From an ethical and governance perspective, it is important to ensure that such technologies are developed responsibly. There should be safeguards to prevent misuse, unintended environmental release, or harmful applications. Transparency, regulation, and continuous monitoring are important to balance innovation with safety. Note: AI tools were used to help clarify concepts and structure this response.

Note: AI tools were used to help clarify concepts and structure this response.