14_Gene Expression

Gene Expression: From Gene to Protein

Overview of Genetic Information Flow

• Genes contain specific sequences of nucleotides in DNA.

• Traits are determined by protein synthesis, directed by DNA.

• Gene expression involves transcription (DNA to RNA) and translation (RNA to protein).

Discovery of Gene-Protein Relationship

• In 1902, Archibald Garrod proposed that genes influence phenotypes through enzymes.

Transcription and Translation Principles

RNA's Role in Protein Synthesis

• RNA serves as a bridge between DNA and protein synthesis.

• Differences from DNA: RNA has ribose sugar and uracil (U) instead of thymine (T), and is usually single-stranded.

Stages of Gene Expression

• Transcription: synthesis of RNA using DNA information, producing mRNA.

• Translation: synthesis of polypeptides utilizing mRNA.

• Ribosomes are the sites of translation.

• In bacteria, translation starts before transcription ends; in eukaryotes, transcription occurs in the nucleus, and processing is required for mRNA before translation.

The Central Dogma of Molecular Biology

• Central Dogma: DNA → RNA → Protein.

The Genetic Code

• Information flow involves a triplet code - sequences of three nucleotides (codons) that correspond to amino acids.

• Codons are non-overlapping, and the mRNA sequence is complementary to DNA.

Transcription Process

• Template strand: one DNA strand is used as a template for RNA transcription.

• mRNA is transcribed in the 5' to 3' direction.

Translation Process

• Codons on mRNA are read in the 5' to 3' direction; each codon designates a specific amino acid, linking to protein formation.

Decoding the Genetic Code

• 64 codons identified including 61 that code for amino acids; 3 act as stop signals.

• Redundancy: multiple codons can code for one amino acid; specificity: each codon corresponds to only one amino acid.

Transcription in Eukaryotes

• Eukaryotic RNA undergoes processing, including 5' capping, polyadenylation, and splicing to remove introns and join exons.

• Spliceosomes facilitate splicing by removing introns.

Translation Overview

Transfer RNA (tRNA)

• Each tRNA has an amino acid and an anticodon that pairs with mRNA codons, ensuring correct amino acid incorporation.

• The structure of tRNA resembles a cloverleaf shape in 2D and L-shaped in 3D.

Ribosomes in Translation

• Ribosomes consist of rRNA and proteins, facilitating the interaction between tRNA and mRNA.

• There are three sites on the ribosome: A (aminoacyl), P (peptidyl), and E (exit).

Stages of Translation

1. Initiation: Assembly of mRNA, initiator tRNA, and ribosomal subunits at the start codon.

2. Elongation: Addition of amino acids to the growing polypeptide chain.

3. Termination: Occurs when a stop codon is reached, releasing the polypeptide.

Mutations and their Effects

Types of Mutations

• Point mutations: changes in a single nucleotide pair.

  • Silent mutations: no effect on protein function.

  • Missense mutations: alter one amino acid in a sequence.

  • Nonsense mutations: create a premature stop codon.

• Insertions and deletions can cause frameshift mutations, altering the reading frame of genetic code.

Role of Mutations in Phenotype

• Some mutations can confer advantages in specific environments.

• Example: Sickle cell allele provides resistance to malaria in heterozygous individuals.

Chromosomal Alterations

• Errors in mitosis or meiosis can lead to changes in chromosome number and structure.

• Nondisjunction results in aneuploidy, leading to conditions such as Turner’s Syndrome or Down Syndrome.

Mechanisms of Increasing Genetic Variation

• Includes horizontal gene transfer in prokaryotes via transformation, transduction, and conjugation.

• Viral recombination is common in RNA viruses like HIV, promoting genetic diversity.