Chapter 16

Learning Objectives

  • Students should be able to:
      - Use the central dogma of molecular biology to explain the link between genotype and phenotype.
      - Use the genetic code to predict how mutations can influence the production of proteins.
      - Compare and contrast different types of mutations such as point mutations versus chromosome mutations and beneficial, neutral, and deleterious mutations.

The Central Dogma of Molecular Biology

  • Definition: The central dogma of molecular biology summarizes the flow of information in cells, explaining the process of converting information in DNA into functioning molecules within the cell.
      - Gene expression:
        - Transcription: This process makes a copy of information from DNA.
        - Translation: This interprets the nucleotide "language" in the mRNA copy into amino acids.

Linking Genotypes to Phenotypes

  • Genetic Information Flow:
      - The flow of genetic information is from DNA to RNA to proteins.
      - Differences in genotype (i.e., the DNA sequence) may cause differences in phenotype.
      - Diagrammatic Representation:
        - DNA (information storage)
        - mRNA (information carrier)
        - Proteins (e.g., melanocortin receptor)

  • Examples with Mice:
      - Mainland mouse:
        - Genotype: G A C C U G
        - Phenotype: Dark coat due to protein expression.
      - Beach mouse:
        - Genotype: G C A A C C U G
        - Phenotype: Light coat due to differing protein expression.

Exceptions to the Central Dogma

  • Not all genes code for mRNAs that are translated into proteins.
      - Some RNAs perform other functions (e.g., tRNA, rRNA) without being translated.
      - Gene Flow Exceptions:
        - Reverse Transcriptase:
          - Some viruses, such as HIV, contain reverse transcriptase which allows the gene flow to be RNA → DNA → RNA and protein.       - HIV operates as a retrovirus causing AIDS.

  • HIV Lifecycle Overview:
      - The virus contains two identical strands of RNA, reverse transcriptase, a viral envelope, and a capsid.
      - The viral RNA forms RNA-DNA hybrids, which integrates into the host cell's nucleus and ultimately leads to new viral RNA and progeny virions exiting the host cell.

The Genetic Code

  • Definition: The genetic code consists of three-letter “words” (codons) indicating specific amino acids.
      - The sequence of codons is referred to as the reading frame.

  • Question: How many different RNA sequences could code for the following amino acid sequence: Met-Trp-Cys-(Stop)?
      - Students are required to write possible sequences.

  • Universality:
      - The genetic code is nearly universal across species, from simple bacteria to complex animals.
      - Transplantation of genes can allow expression across different species (e.g., pigs expressing jellyfish genes, plants expressing firefly genes).

Mutations

  • Definition: A mutation is any permanent change in an organism’s DNA.
      - This typically results in a change in the cell’s genotype and may produce new alleles.
      - Types of Mutations:
        - Point Mutations: Result from one or a small number of base changes.
        - Chromosome-level Mutations: These are larger in scale and can affect the structure or number of chromosomes.

  • Focus on Point Mutations:
      - Consequences of Point Mutations That Alter Codons:
        - Types and Definitions:
          - Silent mutation:
            - Change does not alter the amino acid specified by the codon.
          - Missense mutation:
            - Change alters the amino acid specified by the codon.
          - Nonsense mutation:
            - Change results in an early stop codon.
          - Frameshift mutation:
            - Involves addition or deletion of a nucleotide shifting the reading frame.   

  • Example Table (Consequences of Point Mutations):

    Mutation Type

    Original DNA

    Original mRNA

    Resulting Polypeptide

    Consequence

    Silent

    TAT TGG CTA GTA CAT

    UAU UGG CUA GUA CAU

    Tyr Trp Leu Val His

    No change in phenotype; neutral with respect to fitness

    Missense

    TAC TGG CTA GTA CAT

    UAC UGG CUA GUA CAU

    Tyr-Trp-Leu-Val-His

    Change in primary structure; may be beneficial, neutral, or deleterious

    Nonsense

    TAT TGA CTA GTA CAT

    UAU UGA CUA GUA CAU

    Tyr STOP

    Leads to early termination; usually deleterious

    Frameshift

    TAT TCG GCT AGT ACAT

    UAU UCG GCU AGU ACA U

    Tyr Ser Ala Ser Thr

    Alters subsequent codons; almost always deleterious

  • Further Investigation:
      - Students are tasked to identify the type of mutation in a given sequence where transcription and translation start at the beginning.

Chromosome Alterations

  • Definition: Chromosome alterations may change chromosome number or structure.

  • Types of Chromosome Alterations:
      - Deletion: Loss of a segment of a chromosome.
      - Inversion: A segment of a chromosome is reversed end to end.
      - Duplication: A segment of a chromosome is repeated.
      - Translocation: A segment of one chromosome is transferred to another chromosome.   

  • Visualization of Chromosome Alteration Types:
      - Displays how alterations can be represented and the potential impacts on genetic makeup.