Module 2: Chromosomes & Genes

Module 2: Chromosomes & Genes

• DNA is the hereditary material, encoding the blueprint for all organisms.
• DNA structure consists of nitrogenous bases, deoxyribose sugars, and phosphates, forming nucleotides.
• DNA has four bases: adenine (A), thymine (T), guanine (G), and cytosine (C).
• Purines (A and G) pair with pyrimidines (T and C) via hydrogen bonds, forming stable base pairs.
• DNA forms a double helix structure, protecting genetic information.
• DNA in organisms has varying structures and roles.
• Nuclear DNA: governs cellular functions and traits, organized into chromosomes inherited from both parents.
• Humans have 22 pairs of autosomes and one pair of sex chromosomes.
• Mitochondrial DNA (mtDNA): circular DNA found in mitochondria, crucial for cellular metabolism, inherited maternally, contains 37 genes.
• DNA is organized into progressively compact structures within eukaryotic cells: -DNA wraps around histone proteins to form nucleosomes. -Nucleosomes create a 10nm fiber, known as primary chromatin. -Chromatin loops form a 30nm fiber, further condensing into chromatids.
• Chromosomes: tightly packed DNA structures visible during cell division, enabling efficient gene distribution.
• Euchromatin: loosely packed, accessible for gene expression.
• Heterochromatin: densely packed, generally inactive.
• Chromosomes have a centromere for spindle attachment during division and two arms (p and q).
• Telomeres are protective sequences at chromosome ends maintained by telomerase to prevent gene loss.
• Autosomes (chromosome 1-22): identical in males and females
• Sex chromosomes (X and Y): determine sex (XX in females, XY in males), similar genes but possibly different alleles.
• X chromosome: relatively large; plays a key role in development.
• Y chromosome: smallest human chromosome, carries the SRY gene responsible for male sex determination.
• Humans are diploid (2n), having two complete sets of chromosomes from each parent.
• Aneuploidy: having an abnormal number of chromosomes (e.g., monosomy, trisomy).
• Polyploidy: having more than two sets of chromosomes.
• Genes: functional units of heredity composed of a specific DNA sequence encoding instructions for protein/RNA synthesis.
• Genes consist of coding regions (exons) and non-coding regions (introns).
• Gene expression: DNA is transcribed into mRNA, which is then translated into proteins through a series of steps.

Transcription: From DNA to mRNA

• Transcription is the process of copying a segment of DNA into mRNA.
• mRNA uses uracil (U) in place of thymine (T).
• RNA polymerase II synthesizes mRNA, binding to the DNA promoter region, unwinding DNA, and adding ribonucleotides to the growing mRNA strand (3' to 5' direction).

RNA Processing: Preparing mRNA for Translation

• mRNA undergoes processing before exiting the nucleus.
  • 5' capping: adds a modified guanine nucleotide to protect and facilitate ribosome attachment.
  • Splicing: removes non-coding introns, linking together coding exons (facilitated by spliceosome).
  • Polyadenylation: adds a poly(A) tail (adenine nucleotides) to enhance mRNA stability and transport.

Translation: From mRNA to Protein

• Translation occurs in the cytoplasm: ribosomes bind to mRNA, reading codons which are three-base sequences
• tRNA molecules carry specific amino acids to the ribosome & correctly match mRNA codons.
• Peptide bonds form between amino acids to build a polypeptide chain which eventually becomes a protein.
• mRNA is read in 5' to 3' direction.

Post-Translational Modifications

• Proteins undergo further modifications after translation, altering their function, stability, and location.
• Examples: phosphorylation, acetylation, methylation, glycosylation, lipidation and proteolytic cleavage.

Regulation of Gene Expression

• Gene expression is primarily regulated at the transcription level & controlled by factors.
• RNA-mediated gene expression: microRNAs/siRNAs regulate mRNA stability and translation.

Lyon's Hypothesis: X Chromosome Inactivation

• Females have two X chromosomes; one is randomly inactivated to compensate for dosage differences between sexes.
• Inactivation is permanent in all daughter cells.
• Inactivated X chromosome forms a Barr body, contributing to gene expression differences.