Molecular Basis of Inheritance — Short Notes
Nucleic Acids
- DNA — genetic material in most organisms.
- RNA — genetic material in some viruses; also functions as messenger, transfer, ribosomal.
- Nucleotide = phosphate + pentose sugar (deoxyribose/ribose) + nitrogenous base.
- Bases: Purines — Adenine (A), Guanine (G); Pyrimidines — Cytosine (C), Thymine (T, DNA), Uracil (U, RNA).
DNA Structure (Watson & Crick, 1953)
- Double helix, antiparallel strands (5'→3' and 3'→5').
- Backbone: sugar-phosphate; bases inside; H-bonds between complementary bases.
- Base pairing: A=T (2 H-bonds), G≡C (3 H-bonds) — Chargaff's rule (A=T, G=C).
- Pitch: 3.4 nm; 10 bp per turn; base-pair rise 0.34 nm; diameter 2 nm.
- Right-handed; grooves — major & minor.
DNA Packaging
- Prokaryotes: DNA supercoiled with basic proteins → nucleoid.
- Eukaryotes: DNA + histones (H2A, H2B, H3, H4) → nucleosome (200 bp DNA around octamer of 8 histones). H1 links nucleosomes → chromatin ("beads on a string") → 30-nm fibre → chromosome.
- Euchromatin — loosely packed, transcriptionally active.
- Heterochromatin — tightly packed, inactive.
DNA as Genetic Material — Landmark Experiments
- Griffith (1928) — mice + Streptococcus pneumoniae; discovered transforming principle.
- Avery, MacLeod, McCarty (1944) — showed the transforming principle is DNA, not protein or RNA.
- Hershey & Chase (1952) — bacteriophage T2 with ³²P (DNA) and ³⁵S (protein) → only ³²P enters bacteria → DNA is genetic material.
Properties of a genetic material
Replicate stably · Store information · Undergo mutations · Express as phenotype.
DNA Replication (semi-conservative)
- Meselson & Stahl (1958) — E. coli grown in ¹⁵N; then in ¹⁴N → density-gradient centrifugation shows one intermediate & one light band → semi-conservative confirmed.
- Enzymes:
- Helicase — unwinds DNA.
- DNA polymerase — adds nucleotides 5'→3' only.
- Primase — makes RNA primers.
- Ligase — seals gaps (Okazaki fragments).
- Topoisomerase / gyrase — relieves supercoiling.
- Leading strand — continuous. Lagging strand — discontinuous → Okazaki fragments.
Transcription (DNA → RNA)
- Only one strand (template, 3'→5') is used; coding/sense strand has the same sequence as RNA except T↔U.
- Requires RNA polymerase (prokaryotes have one; eukaryotes have three: I, II, III).
- Stages: initiation → elongation → termination.
- Prokaryotes: no separate nucleus → mRNA is used directly for translation, often co-transcriptionally.
- Eukaryotes: primary transcript = hnRNA; contains exons (coding) and introns (non-coding).
- Splicing removes introns.
- Capping — methylguanosine at 5' end.
- Tailing — poly-A tail at 3' end.
- Only then is mature mRNA exported to cytoplasm.
Genetic Code
- Triplet, degenerate, unambiguous, universal, non-overlapping, comma-less.
- 64 codons: 61 code for 20 amino acids + 3 stop codons (UAA, UAG, UGA).
- Initiator codon: AUG (Methionine).
tRNA
- Adapter molecule (Crick's hypothesis).
- Cloverleaf 2D; L-shaped 3D.
- Has anticodon loop (pairs with mRNA codon) + amino acid attachment site (3'-CCA).
Translation
- Ribosome binds mRNA. Small subunit binds first + initiator tRNA.
- Large subunit joins → sites: A (aminoacyl), P (peptidyl), E (exit).
- 23S rRNA (prokaryotes) is the peptidyl transferase — a ribozyme.
- Termination: release factor recognises stop codon → polypeptide released.
Regulation of Gene Expression
Lac operon (Jacob & Monod, 1961) — negative regulation
- Structural genes: z (β-galactosidase), y (permease), a (transacetylase).
- Operator (o) + promoter (p) + regulator (i, upstream).
- Absent lactose: i produces repressor → binds o → RNA pol blocked → no transcription.
- Present lactose: lactose (as allolactose) binds repressor → repressor detaches → transcription ON.
Human Genome Project (1990–2003)
- Sequenced entire human genome (~3.1 × 10⁹ bp).
- ~30,000 genes (initially thought ~1 lakh).
- Chromosome 1 has the most genes; Y has fewest.
- 99.9% of DNA identical between any two humans; SNPs = variations.
- Coding sequences ~2%.
DNA Fingerprinting
- Developed by Alec Jeffreys (1985).
- Uses VNTRs (variable number tandem repeats) — highly polymorphic.
- Applications: forensic, paternity, pedigree tracing.
- Technique: DNA isolation → digestion (restriction enzymes) → electrophoresis → Southern blot → hybridise with VNTR probe → autoradiography.
Key take-aways
- DNA carries information via base sequence; A-T, G-C pairing enables both fidelity and copying.
- Central Dogma: DNA → transcription → RNA → translation → protein.
- Genetic code is universal (with rare exceptions) — powerful evidence for common ancestry.
- Modern genomics (HGP, DNA fingerprinting) has transformed medicine, forensics, and evolution studies.
Molecular Basis of Inheritance — Short Notes
Nucleic Acids
- DNA — genetic material in most organisms.
- RNA — genetic material in some viruses; also functions as messenger, transfer, ribosomal.
- Nucleotide = phosphate + pentose sugar (deoxyribose/ribose) + nitrogenous base.
- Bases: Purines — Adenine (A), Guanine (G); Pyrimidines — Cytosine (C), Thymine (T, DNA), Uracil (U, RNA).
DNA Structure (Watson & Crick, 1953)
- Double helix, antiparallel strands (5'→3' and 3'→5').
- Backbone: sugar-phosphate; bases inside; H-bonds between complementary bases.
- Base pairing: A=T (2 H-bonds), G≡C (3 H-bonds) — Chargaff's rule (A=T, G=C).
- Pitch: 3.4 nm; 10 bp per turn; base-pair rise 0.34 nm; diameter 2 nm.
- Right-handed; grooves — major & minor.
DNA Packaging
- Prokaryotes: DNA supercoiled with basic proteins → nucleoid.
- Eukaryotes: DNA + histones (H2A, H2B, H3, H4) → nucleosome (200 bp DNA around octamer of 8 histones). H1 links nucleosomes → chromatin ("beads on a string") → 30-nm fibre → chromosome.
- Euchromatin — loosely packed, transcriptionally active.
- Heterochromatin — tightly packed, inactive.
DNA as Genetic Material — Landmark Experiments
- Griffith (1928) — mice + Streptococcus pneumoniae; discovered transforming principle.
- Avery, MacLeod, McCarty (1944) — showed the transforming principle is DNA, not protein or RNA.
- Hershey & Chase (1952) — bacteriophage T2 with ³²P (DNA) and ³⁵S (protein) → only ³²P enters bacteria → DNA is genetic material.
Properties of a genetic material
Replicate stably · Store information · Undergo mutations · Express as phenotype.
DNA Replication (semi-conservative)
- Meselson & Stahl (1958) — E. coli grown in ¹⁵N; then in ¹⁴N → density-gradient centrifugation shows one intermediate & one light band → semi-conservative confirmed.
- Enzymes:
- Helicase — unwinds DNA.
- DNA polymerase — adds nucleotides 5'→3' only.
- Primase — makes RNA primers.
- Ligase — seals gaps (Okazaki fragments).
- Topoisomerase / gyrase — relieves supercoiling.
- Leading strand — continuous. Lagging strand — discontinuous → Okazaki fragments.
Transcription (DNA → RNA)
- Only one strand (template, 3'→5') is used; coding/sense strand has the same sequence as RNA except T↔U.
- Requires RNA polymerase (prokaryotes have one; eukaryotes have three: I, II, III).
- Stages: initiation → elongation → termination.
- Prokaryotes: no separate nucleus → mRNA is used directly for translation, often co-transcriptionally.
- Eukaryotes: primary transcript = hnRNA; contains exons (coding) and introns (non-coding).
- Splicing removes introns.
- Capping — methylguanosine at 5' end.
- Tailing — poly-A tail at 3' end.
- Only then is mature mRNA exported to cytoplasm.
Genetic Code
- Triplet, degenerate, unambiguous, universal, non-overlapping, comma-less.
- 64 codons: 61 code for 20 amino acids + 3 stop codons (UAA, UAG, UGA).
- Initiator codon: AUG (Methionine).
tRNA
- Adapter molecule (Crick's hypothesis).
- Cloverleaf 2D; L-shaped 3D.
- Has anticodon loop (pairs with mRNA codon) + amino acid attachment site (3'-CCA).
Translation
- Ribosome binds mRNA. Small subunit binds first + initiator tRNA.
- Large subunit joins → sites: A (aminoacyl), P (peptidyl), E (exit).
- 23S rRNA (prokaryotes) is the peptidyl transferase — a ribozyme.
- Termination: release factor recognises stop codon → polypeptide released.
Regulation of Gene Expression
Lac operon (Jacob & Monod, 1961) — negative regulation
- Structural genes: z (β-galactosidase), y (permease), a (transacetylase).
- Operator (o) + promoter (p) + regulator (i, upstream).
- Absent lactose: i produces repressor → binds o → RNA pol blocked → no transcription.
- Present lactose: lactose (as allolactose) binds repressor → repressor detaches → transcription ON.
Human Genome Project (1990–2003)
- Sequenced entire human genome (~3.1 × 10⁹ bp).
- ~30,000 genes (initially thought ~1 lakh).
- Chromosome 1 has the most genes; Y has fewest.
- 99.9% of DNA identical between any two humans; SNPs = variations.
- Coding sequences ~2%.
DNA Fingerprinting
- Developed by Alec Jeffreys (1985).
- Uses VNTRs (variable number tandem repeats) — highly polymorphic.
- Applications: forensic, paternity, pedigree tracing.
- Technique: DNA isolation → digestion (restriction enzymes) → electrophoresis → Southern blot → hybridise with VNTR probe → autoradiography.
Key take-aways
- DNA carries information via base sequence; A-T, G-C pairing enables both fidelity and copying.
- Central Dogma: DNA → transcription → RNA → translation → protein.
- Genetic code is universal (with rare exceptions) — powerful evidence for common ancestry.
- Modern genomics (HGP, DNA fingerprinting) has transformed medicine, forensics, and evolution studies.