Molecular Biology - NEET 2026

DNA, RNA & The Central Dogma

The flow of information: DNA → RNA → Protein. Know every enzyme and every step.

DNA Structure

Watson-Crick model (1953): Double helix, right-handed (B-form). Two antiparallel strands — one 3'→5', other 5'→3'.

Base pairing (Chargaff's rule): A=T (2 H-bonds), G≡C (3 H-bonds). [A]=[T], [G]=[C]. G+C rich DNA is more stable (melts at higher temperature).

Nucleotide = Sugar (deoxyribose) + Phosphate + Nitrogenous base. Purines: A, G (double ring). Pyrimidines: T, C, U (single ring). DNA has T; RNA has U instead.

Packaging: DNA → Nucleosome (DNA wound 1.65 times around 8 histones: 2 each of H2A, H2B, H3, H4). H1 is linker histone. Nucleosome → 30nm fibre → loops → chromosomes.

DNA Replication

Semi-conservative: Each new DNA has one parental + one new strand. Proved by Meselson and Stahl using ¹⁵N labelling in E. coli.

Key enzymes: Helicase (unwinds double helix), Primase (synthesises RNA primer), DNA polymerase III (main enzyme — 5'→3' synthesis only), DNA polymerase I (removes primers, fills gaps), DNA ligase (joins Okazaki fragments).

Leading strand: Continuous synthesis (5'→3' toward replication fork). Lagging strand: Discontinuous, Okazaki fragments (5'→3' away from fork).

Transcription

Template strand: 3'→5' direction (read by RNA pol). mRNA is synthesised 5'→3', complementary to template strand.

In prokaryotes: Single RNA polymerase. Promoter recognised by sigma factor. No RNA processing — direct translation begins.

In eukaryotes: RNA Pol I (rRNA), RNA Pol II (mRNA/pre-mRNA), RNA Pol III (tRNA, 5S rRNA). Pre-mRNA → 5' capping → 3' polyadenylation → splicing (introns removed, exons joined by spliceosome) → mature mRNA exported to cytoplasm.

Translation (Protein Synthesis)

Genetic code: 64 codons, 61 sense + 3 stop (UAA, UAG, UGA). AUG = start codon (methionine). Code is degenerate (many codons → one amino acid), universal, non-overlapping, non-ambiguous.

tRNA: Anticodon loop reads mRNA codon. CCA at 3' end accepts amino acid. Wobble hypothesis — first position of anticodon can pair with multiple codons.

Ribosome: 80S (cytoplasm) — A site (aminoacyl), P site (peptidyl), E site (exit). Peptide bond formed by peptidyl transferase (23S rRNA — ribozyme activity).

Mutations & Human Genome Project

Point mutations: Transition (purine→purine or pyrimidine→pyrimidine) vs Transversion (purine↔pyrimidine). Silent mutation (no AA change — degeneracy). Missense (wrong AA). Nonsense (creates stop codon → premature termination). Frameshift (insertion/deletion — shifts reading frame, catastrophic).

HGP: 3164.7 Mb genome. ~30,000 protein-coding genes. 99.9% identical between humans. ~1.4 million SNPs identified. Shotgun sequencing used. Completed 2003.

Molecular Biology Fact Vault

Direct recall facts — these appear verbatim in NEET questions.

Key Enzymes in Replication

Helicase: unwinds DNA
Primase: RNA primer synthesis
DNA pol III: new strand synthesis
DNA pol I: primer removal + gap fill
DNA ligase: seals nicks

DNA polymerase can only add nucleotides in 5'→3' direction — why lagging strand is discontinuous

Genetic Code Features

64 total codons
61 sense (code for AA)
3 stop: UAA, UAG, UGA
1 start: AUG (Met)
Degenerate: Yes
Universal: Yes (with exceptions)
Non-overlapping: Yes

Leucine has 6 codons (most). Methionine and Tryptophan have only 1 codon each

DNA vs RNA

DNA: deoxyribose, T, double-stranded, stable
RNA: ribose, U, usually single-stranded
DNA purines: A, G
DNA pyrimidines: C, T
RNA: C, U replaces T

A=T (2 H-bonds), G≡C (3 H-bonds). GC-rich = more stable = higher Tm

Meselson-Stahl Experiment

Used ¹⁴N and ¹⁵N (heavy) nitrogen
E. coli grown in ¹⁵N medium
Transferred to ¹⁴N
After 1 generation: hybrid band
After 2 generations: hybrid + light
Proved: Semi-conservative replication

CsCl density gradient centrifugation used to separate DNA bands by density

Worked Examples

Molecular biology has 4–5 NEET questions annually — master these patterns.

EasyWhich enzyme is responsible for removing RNA primers during DNA replication in E. coli?▾

(A) Helicase (B) DNA polymerase I (C) DNA polymerase III (D) Ligase

DNA polymerase I has 5'→3' exonuclease activity to remove RNA primers AND 5'→3' polymerase activity to fill the gaps. DNA polymerase III is the main replication enzyme. Ligase seals the nicks.

Answer: (B) DNA polymerase I

MediumIf one strand of DNA has the sequence 3'-ATCGTA-5', what is the mRNA sequence transcribed from it?▾

Template strand (3'→5'): ATCGTA. mRNA is complementary and antiparallel to template strand. A→U, T→A, C→G, G→C. Template 3'→5': A-T-C-G-T-A. mRNA 5'→3': U-A-G-C-A-U.

Answer: 5'-UAGCAU-3'

Key: mRNA is same sequence as coding strand (non-template strand) with T replaced by U

HardA segment of DNA has 20% adenine. What percentage of guanine does it contain?▾

Chargaff's rule: [A]=[T] and [G]=[C]. If A=20%, then T=20%. Total A+T = 40%. Remaining = 60% for G+C. G=C=30% each.

Answer: 30% Guanine

Mistake DNA

These errors recur in NEET year after year.

❌ Confusing template strand with coding strand

Template strand (antisense) is READ by RNA polymerase (3'→5'). Coding strand (sense/non-template) has the SAME sequence as mRNA (with T instead of U). NEET questions often give the coding strand and ask about mRNA.

Fix: mRNA = same as coding strand (T→U). Template strand is the mirror image.

❌ Saying replication is conservative

Replication is SEMI-conservative — each daughter molecule has one parental and one new strand. Conservative (both new in one, both old in other) was disproved by Meselson-Stahl.

Fix: Semi = half old, half new. The experiment showed this clearly at generation 1.

❌ Confusing stop codons

Stop codons: UAA (ochre), UAG (amber), UGA (opal). There is NO stop codon in DNA directly — students confuse the nomenclature. AUG is the universal start codon (except in some organelles).

Fix: Three stops: UAA, UAG, UGA. One start: AUG. No tRNA recognises stop codons — release factors do.

Chapter Intelligence

PYQ Frequency

DNA structure/Chargaff: 1 Q/year
Replication enzymes: 1 Q/year
Transcription/translation: 1–2 Q/year
Genetic code features: 1 Q/year

2026 Prediction

High: Replication enzyme function question
Expected: Template vs coding strand confusion trap
Watch: Differences in eukaryote vs prokaryote transcription

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