Human Genetics 28

Class Reminders

  • Quizzes and Discussions
      - Today: Chapter 9
      - Next Week: Chapter 10
      - Chapter 12 Coverage starts Monday

  • Exam Schedule
      - Next Exam: Friday, September 10   - Requests for alternative exam locations must be submitted with documentation if you have a disability.

Transcription and Translation Overview

  • Focus on the processes of transcription and translation in gene expression.

Transcription

  • Definition: The process of synthesizing RNA from a DNA template.

  • Different proteins are necessary for transcription, which include transcription factors and RNA polymerase.

Key Components

  • Transcription Factors: Proteins that bind to the promoter to initiate transcription.
      - Example: TATA binding protein (TBP).

  • Gene Structure:
      - Components of a gene:
        - Promoter: Sequence where transcription starts.
        - Coding Sequence: Region that codes for proteins.
        - Terminator: Sequence signaling where transcription ends.   - Only about 3-5% of the genome is made up of these coding regions.

The Process of Transcription

  1. Initiation:
       - Transcription factors and RNA polymerase bind to the promoter.
       - Specific sequences, such as the TATA box (average sequence: TATAAA), play a critical role in this binding.

  2. Elongation:
       - RNA polymerase unwinds the DNA strand, acting like a helicase.
       - RNA nucleotides bond with the DNA template and are added sequentially to the growing RNA strand.    - Only one strand of the DNA is transcribed at a time.

  3. Termination:
       - RNA polymerase continues until it reaches the terminator sequence, which signals it to stop transcription.    - If the terminator is mutated or missing, transcription could continue indefinitely, potentially leading to adverse effects.

Multiple RNA Polymerases

  • Multiple RNA polymerases can transcribe the same gene simultaneously, enhancing the rate of transcription.

  • This feature is significant during rapid cell division and growth processes, like embryonic development.

RNA Processing

  • RNA undergoes several processing steps before it can exit the nucleus, notably:   1. 5' Capping: Addition of a methylated cap to the start of mRNA, aiding in ribosome recognition.   2. 3' Polyadenylation: Addition of a poly-A tail to the end of mRNA, stabilizing it and facilitating translation.   3. Splicing: Removal of introns (non-coding regions) and joining of exons (coding regions) to form a mature mRNA.

Splicing Details

  • Exons: Segments of mRNA that code for proteins.

  • Introns: Non-coding segments that are removed during splicing.

  • The Spliceosome: Complex responsible for removing introns during RNA processing.

  • Alternative Splicing: A process that allows different combinations of exons to be included in the final mRNA, creating varying protein isoforms from the same gene.   - Key Point: This can lead to the production of proteins with related but distinct functions, crucial in cellular differentiation.

Gene Count and Protein Diversity

  • Initial estimations suggested humans have approximately 100,000 genes based on protein spotting; however, we have about 25,000 genes.

  • Discovery: Each gene can produce multiple proteins due to alternative splicing (approx. 4 different isoforms on average).

Translation

  • Definition: The process of synthesizing proteins from an mRNA template.

The Genetic Code

  • Codon Table:
       - Codons are triplets of RNA bases that translate into specific amino acids.    - There are 64 codons (4^3 combinations) accounting for redundancy—more than one codon can code for the same amino acid.    - Start Codon: AUG (also codes for methionine).    - Stop Codons: UAA, UAG, UGA (do not code for amino acids).

Key Concepts of Translation

  • Open Reading Frame (ORF): A continuous stretch of codons, which does not contain stop codons.

  • Non-overlapping Code: Each nucleotide is part of one codon, maintaining clear signal integrity.

  • Universal Code: Most organisms use the same codon table, with some exceptions in archaeal species.

Mutations in Translation

  • Frame Shift Mutations: Caused by insertions or deletions that disrupt the reading frame, often leading to significant changes in the resulting protein.

  • Missense Mutations: Amino acid substitutions due to nucleotide changes.

  • Nonsense Mutations: Introduce premature stop codons into the sequence, leading to truncated proteins.

Conclusion

  • The processes of transcription and translation are pivotal in gene expression, and understanding these processes aids in comprehending genetics, cell biology, and molecular biology's intricacies.

  • Further examinations of mutations and alternative splicing processes reveal the complexity underlying genetic information and protein diversity in organisms.