Lecture on Gene Expression and Protein Synthesis

Page 1: Introduction to Gene Expression

Figure 17.1: Description of a population of albino donkeys on Asinara, Italy.
- A recessive mutation disabling pigment synthesis arose in a single donkey's DNA.
- This mutation was passed down generations, leading to a large population of homozygous albino donkeys.
Process for studying gene expression:
- Mastering Biology Resources:
- eText and Study Area contents.
- BioFlix® Animations:
- Protein Synthesis Overview.
Key Concepts Introduced in Chapter 17:
- 17.1 Genes specify proteins via transcription and translation (p. 336)
- 17.2 Transcription is the DNA-directed synthesis of RNA (p. 342)
- 17.3 Eukaryotic cells modify RNA after transcription (p. 345)
- 17.4 Translation is RNA-directed synthesis of a polypeptide (p. 347)
- 17.5 Mutations affecting protein structure and function (p. 357)

Concept 17.1: Genes specify proteins via transcription and translation
- Inherited traits are determined by genes with specific nucleotide sequences in DNA.
- Genes dictate protein synthesis through two main stages:
1. Transcription
2. Translation
- Example of coat color:
- Normal enzyme synthesizes pigment (normal trait).
- Faulty enzyme leads to albino phenotype.
- Proteins are the link between genotype (genetic makeup) and phenotype (observable traits).

Foundational Work in Genetics:
- Archibald Garrod (1902): Proposed that genes dictate phenotype through enzymes, associating symptoms of genetic diseases with enzyme deficiencies.
- Example: Alkaptonuria is linked to inability to produce an enzyme breaking down alkapton, resulting in black urine.
One Gene–One Enzyme Hypothesis:
- Early 20th-century studies confirmed Garrod’s hypothesis that specific genes produce specific enzymes (later restated as one gene – one polypeptide).

Nutritional Mutants in Neurospora crassa:
- Beadle and Ephrussi studied how mutations in Drosophila affect eye color related to pigment synthesis.
- Neurospora experiments: Did mutations in genes causing nutritional deficiencies:
1. Bombarded Neurospora with X-rays to induce mutation.
2. Identified cells unable to grow on minimal medium as mutants.
3. Wild-type Neurospora: Grows on minimal medium by metabolizing all nutrients.
Results:
- Via follow-up studies, mutants requiring additional nutrients were classified based on their metabolic capabilities.
- Strong support for one gene–one enzyme hypothesis: Each mutant phenotype correlated with a specific gene defect.

Transcription and Translation Basics:
- Central Dogma: Describes the flow of genetic information as:
- DNA → RNA → Protein
- RNA synthesis involves the enzyme RNA polymerase, which generates RNA from a DNA template.
Key Differences Between Eukaryotic and Prokaryotic Cells:
- Eukaryotic cells have compartmentalized processes (transcription in nucleus, translation in cytoplasm).
- Bacterial cells can translate mRNA as soon as it is transcribed due to lack of compartmentalization.

Steps in Transcription:
- Initiation: RNA polymerase binds to promoter region of DNA (involves transcription factors).
- Elongation: RNA polymerase unwinds DNA, adding RNA nucleotides complementary to template strand.
- Termination: Occurs when RNA polymerase transcribes a termination signal in the DNA.
- Eukaryotic Specifics: Modifications (5' cap and polyadenylation) made after transcription before mRNA leaves the nucleus.

RNA Processing Overview:
- mRNA undergoes processing to become functional:
- 5' cap added for stability and ribosome attachment.
- 3' poly-A tail added for stability and export from the nucleus.
- Splicing: Removal of introns and joining of exons to create a coding sequence in the mature mRNA.
Function of Introns and Exons:
- Introns are noncoding segments that can regulate gene expression or allow for evolutionary advantages through alternative splicing.

Translation Process:
- mRNA translated into polypeptide at ribosome with the help of tRNA.
- Each tRNA binds a specific amino acid and recognizes the corresponding mRNA codon with its anticodon.
Ribosome Composition and Function:
- Composed of rRNA and proteins, facilitating the binding of tRNA and mRNA during protein synthesis.
- Coordinates the three phases of translation: initiation, elongation, and termination.

Types of Mutations:
- Substitutions: Silent, missense, and nonsense mutations affecting mRNA and final protein structure/function.
- Insertions/Deletions: Frameshift mutations changing reading frames and leading to extensive missense or early termination.
- Consequences: Mutations can arise spontaneously or be caused by mutagens, including physical and chemical agents.

CRISPR-Cas9 System:
- A revolutionary method for editing genes in living organisms.
- Enables targeted alterations within the genome, with applications in treating genetic diseases.
Ethical Concerns:
- Discussions around potential misuse of gene editing technologies highlight the importance of establishing guidelines for research and application.
Definition Reassessment of a Gene:
- A gene is now defined as a segment of DNA that can express to produce either a functional polypeptide or RNA molecule, evolving over time in definition as our understanding of genetics has deepened.