Lecture #4

Genes and Mitosis

Introduction to Genes and the Cell

Genes are segments of DNA that encode instructions for building proteins, which carry out essential functions in cells. The cell cycle is the series of events that cells go through as they grow and divide. Mitosis is the process by which a cell divides to produce two identical daughter cells, crucial for growth, repair, and maintenance in multicellular organisms.

• Gene: A sequence of DNA that codes for a specific protein.

• Cell Cycle: The ordered sequence of events that leads to cell division and duplication.

• Mitosis: The division of a cell's nucleus followed by division of the cytoplasm, resulting in two genetically identical cells.

• Application: Mitosis is essential for tissue growth and repair.

Mutations and Protein Synthesis

How Mutations Affect Proteins

Mutations are changes in the DNA sequence that can alter the structure and function of proteins. The genetic code is read in triplets (codons) during translation, and each codon specifies an amino acid. Mutations can be classified based on their effect on the DNA sequence and the resulting protein.

• Substitution Mutation: One nucleotide is replaced by another, potentially changing a single amino acid in the protein.

• Insertion Mutation: An extra nucleotide is added, which can shift the reading frame (frameshift mutation) and alter the entire downstream protein sequence.

• Deletion Mutation: A nucleotide is removed, also potentially causing a frameshift.

• Codon Table: Used to determine which amino acids are encoded by specific mRNA codons.

Example:

• Original sequence: CU-GGU... = threonine-glycine

• Substitution (C-U): CU-GGU... = threonine-glycine

• Insertion (insert A before C): AC-UGG-U... = tyrosine-tryptophan-?

• Deletion (remove first C): UG-GU... = leucine-?

Formula:

• Number of possible codons: $4^3 = 64$ (since there are 4 nucleotides and codons are triplets)

Codon Table (Main Purpose: Translation of mRNA to Amino Acids)

Codon	Amino Acid
UUU, UUC	Phe (Phenylalanine)
UUA, UUG, CUU, CUC, CUA, CUG	Leu (Leucine)
AUG	Met (Methionine, Start)
UAA, UAG, UGA	Stop
Other codons	Various amino acids (see full codon table)

Consequences of Mutations

Impact on Health and Disease

Not all mutations result in disease; some are silent or occur in non-critical regions of proteins. However, mutations in essential genes can lead to serious health conditions. The National Center for Biotechnology Information (NCBI) lists hundreds of thousands of protein modifications associated with diseases.

• Silent Mutation: No change in protein function.

• Pathogenic Mutation: Can cause diseases such as:

  • Cystic fibrosis

  • Sickle cell anemia

  • Beta thalassemia

  • Retinitis pigmentosa (RPE65)

  • Fragile X syndrome

  • Hemophilia A and B

  • Neurofibromatosis type I and II

  • Osteogenesis imperfecta

• Example: Sickle cell anemia is caused by a single nucleotide substitution in the beta-globin gene.

Gene Therapy

Modern Approaches to Treating Genetic Diseases

Gene therapy involves correcting defective genes responsible for disease development. Recent advances have led to successful treatments for previously incurable conditions.

• Gene Therapy: Introduction, removal, or alteration of genetic material within a patient's cells to treat disease.

• Applications:

  • Cures for blindness (2017)

  • Treatment for acute lymphoblastic leukemia (ALL)

  • Sickle cell anemia cure (2017)

  • Treatment for epidermolysis bullosa ("butterfly children")

• Ethical Considerations: In the US, gene therapy is generally approved for somatic cells but not for germline cells (egg and sperm), to prevent passing modifications to future generations.

Example: The "3 parent" technique replaces defective mitochondria in an egg with healthy mitochondria from a donor.

Cell Cycle and Mitosis

Phases of the Cell Cycle

The cell cycle consists of interphase (growth and DNA replication) and mitotic phase (division). Interphase is subdivided into G1 (growth), S (DNA synthesis), and G2 (preparation for mitosis).

• Interphase: Period of cell growth and DNA replication.

• Mitosis: Division of the nucleus, followed by cytokinesis (division of the cytoplasm).

• Phases of Mitosis:

  • Prophase: Chromosomes condense, nuclear envelope breaks down.

  • Metaphase: Chromosomes align at the cell's equator.

  • Anaphase: Sister chromatids separate and move to opposite poles.

  • Telophase: Nuclear envelopes reform, chromosomes decondense.

  • Cytokinesis: Cytoplasm divides, forming two daughter cells.

Formula:

• Number of chromosomes after DNA replication: $2n$ (where $n$ is the haploid number; in humans, $n=23$ so $2n=46$)

Tumors and Cell Death

Abnormal Cell Proliferation and Death

Tumors arise from uncontrolled cell division. They can be benign (noncancerous) or malignant (cancerous). Cell death can occur via programmed processes (apoptosis, autophagy) or due to injury (necrosis).

• Benign Tumor: Does not invade other tissues; often treated by observation or removal.

• Malignant Tumor: Invades other tissues and can metastasize; treated by surgery, chemotherapy, or radiation.

• Apoptosis: Programmed cell death, essential for development and tissue homeostasis.

• Autophagy: "Self-eating" process where cells degrade their own components to survive starvation or remove damaged organelles.

• Necrosis: Uncontrolled cell death due to injury or damage.

Example: Apoptosis removes webbing between fingers during embryonic development.

Additional info: Autophagy and apoptosis are tightly regulated processes; dysregulation can contribute to diseases such as cancer or neurodegeneration.