Revision: Genetics and Evolution >> Molecular Basis of Inheritance Biology (Theory) ISC (Science) ISC Class 12 CISCE

A nucleotide is the basic structural unit of nucleic acids, composed of a nitrogenous base, a pentose sugar, and a phosphate group.

A nitrogenous base is an organic molecule (purine or pyrimidine) that carries genetic information in nucleic acids.

RNA is a single-stranded nucleic acid that helps in protein synthesis and information transfer.

A nucleoside consists of a nitrogenous base linked to a pentose sugar without a phosphate group.

The unit formed by joining the anomeric carbon of the furanose (sugar) with a nitrogen of a base is called nucleoside.

DNA is a double-stranded nucleic acid that stores and transmits hereditary information and can replicate itself.

Nucleic acids are large biological macromolecules that store and transmit genetic information in living organisms.

A polynucleotide is a long chain formed by the joining of many nucleotide monomers.

When DNA directs the synthesis of DNA itself, then such function of DNA is called autocatalytic function. Eg. Replication.

When DNA directs the synthesis of chemical molecules other than itself, then such functions of DNA are called heterocatalytic functions. Eg, Synthesis of RNA (transcription), synthesis of protein (Translation), etc.

The process by which DNA duplicates itself is called replication. 

Conservative replication is a mode of DNA replication in which the original parental DNA molecule remains intact, and a completely new DNA molecule is synthesised.

Conservative Replication

Dispersive replication is a mode of DNA replication in which the parental DNA is broken into fragments, and each daughter DNA molecule contains a mixture of old and new DNA segments.

Dispersive replication

Semi-conservative replication is a mode of DNA replication in which each daughter DNA molecule consists of one parental (old) strand and one newly synthesized strand.

Semi-Conservative Replication

A sudden change that occurs in the nucleotide sequence of a gene, causing either a minor or considerable change in the characters of an individual is known as mutation.

The movement of the ribosome from one end of the mRNA to the other end by the distance of one triplet codon during translation is known as translocation.

Translation is the process by which tRNA having anticodon to the codon on the mRNA, supplies amino acids, as per the message on mRNA.

A sequence of three adjacent nucleotides in mRNA that codes for one amino acid is known as a codon.

Central dogma is the principle that genetic information flows in one direction in a cell, from DNA to RNA to protein.

or

Central Dogma is the process by which genetic information flows from DNA to RNA to protein, controlling cellular functions and body structure.

Reverse transcription is the process by which DNA is synthesized from an RNA template.

\[\mathrm{RNA}\quad\xrightarrow{\text{reverse transcription}}\quad\mathrm{DNA}\quad\xrightarrow{\text{transcription}}\quad\mathrm{mRNA}\quad\xrightarrow{\text{translation}}\quad\mathrm{Protein}\]

A sequence of three nucleotides on mRNA that codes for a specific amino acid is called a triplet codon.

Transfection is the process of inserting a vector into eukaryotic cells.

The process by which a very long DNA molecule is compactly organised inside the cell nucleus so that it fits within the limited nuclear space and remains functional is called DNA packaging.

Positively charged basic proteins rich in lysine and arginine that associate with DNA to help in its packing in eukaryotic cells are called histones.

A structural unit composed of eight histone protein molecules around which DNA is wrapped is called histone octamer.

The basic repeating unit of chromatin formed by DNA wrapped around a histone octamer is called nucleosome.

Proteins other than histones that are associated with chromatin and help in higher-order DNA packaging and regulation are called non-histone chromosomal (NHC) proteins.

Nucleoid is the region in prokaryotic cells where DNA is organized and associated with proteins, despite the absence of a true nucleus.

The thread-like complex of DNA and proteins present in the nucleus of eukaryotic cells is called chromatin.

Constitutive genes are genes that are continuously expressed irrespective of environmental conditions.

Constitutive enzymes are enzymes that are synthesized continuously and are essential for basic cellular metabolism.

An inducer is a small molecule that activates gene expression by initiating the synthesis of specific enzymes.

Inducible proteins are enzymes that are synthesized only in the presence of a specific inducer or substrate.

A co-repressor is a substance which, when present in excess, binds with a repressor to switch off gene expression.

The technique of identifying an individual by analyzing the unique DNA sequence present in each person, similar to fingerprints, is called DNA fingerprinting.

• DNA is the primary genetic material in most organisms, while RNA acts as genetic material in some viruses.
• A genetic material must be capable of replication, which both DNA and RNA can achieve through base pairing.
• DNA is chemically and structurally more stable than RNA because it lacks the reactive 2′-OH group and contains thymine instead of uracil.
• Both DNA and RNA can undergo mutations, but RNA mutates faster due to its unstable nature, leading to rapid evolution in RNA viruses.
• DNA stores genetic information efficiently, whereas RNA helps in expression and transmission of genetic information through protein synthesis.

• Discovery of Ribozymes - Sidney Altman and Thomas Cech independently discovered that RNAs can act as biocatalysts.
• RNA World hypothesis - The RNA World hypothesis suggests that early life was based exclusively on nucleic acids, most probably RNA, and was first proposed by Carl Woese, Francis Crick, and Leslie Orgel in 1960.
• Evidence for RNA World - RNA is found abundantly in all living cells, structurally related to DNA, and can evolve, replicate, and catalyse reactions.
• Formation of primitive cells - RNA molecules underwent replication, mutation, and developed their own machinery to form primitive cells.
• Formation of DNA - Double-stranded DNA formed eventually, resulting in rich biodiversity.

• Nucleic acids are biomacromolecules present in the acid-insoluble fraction and are responsible for the storage and transmission of genetic information (DNA and RNA).
• They are polynucleotides, formed by repeated units called nucleotides.
• Each nucleotide consists of three components: a nitrogenous base, a pentose sugar, and a phosphate group.
• Nitrogenous bases are of two types: purines (adenine, guanine) and pyrimidines (cytosine, thymine, uracil).
• The sugar present is either ribose (in RNA) or 2′-deoxyribose (in DNA).
• DNA is double-stranded and contains bases A, T, G, and C, while RNA is single-stranded and contains A, U, G, and C.
• DNA stores genetic information, while RNA plays a key role in protein synthesis and the expression of genetic information.

• DNA was established as the primary genetic material and formally modeled as a double helix by Watson and Crick in 1953.
• The structural blueprint relied heavily on Erwin Chargaff’s chemical base equivalence rules and Rosalind Franklin’s X-ray diffraction data.
• The fundamental building block of DNA is a nucleotide, which comprises a five-carbon deoxyribose sugar, a phosphate group, and a nitrogenous base.
• A nucleotide is distinct from a nucleoside, as a nucleoside contains only the nitrogenous base and pentose sugar without the attaching phosphate group.
• The double helix is formed by two antiparallel polynucleotide chains running in opposite directions (5′→3′ and 3′→5′) coiled in a clockwise, right-handed fashion.
• The physical architecture places the hydrophilic sugar-phosphate backbone on the exterior, while the information-carrying nitrogenous bases stack flat on the interior.
• Structural stability is maintained horizontally by complementary base pairing (A=T via two hydrogen bonds; G=C via three hydrogen bonds) and vertically by strong covalent phosphodiester bonds.

• Nature of RNA: RNA is usually a single-stranded nucleic acid molecule.
• Composition: RNA is composed of nucleotides containing ribose sugar, phosphate group, and a nitrogenous base.
• Nitrogenous Bases: RNA contains four bases—adenine (A), guanine (G), cytosine (C), and uracil (U); uracil replaces thymine.
• Base Pairing: Adenine pairs with uracil, while guanine pairs with cytosine.
• Backbone Structure: The RNA backbone consists of alternating ribose sugar and phosphate groups.

• Ribosomal RNA (rRNA) is the most abundant RNA, constituting about 80% of the total cellular RNA.
• It is single-stranded and the most stable form of RNA with the highest molecular weight.
• rRNA is a major structural and functional component of ribosomes.
• It helps bind mRNA and tRNA to ribosomes during protein synthesis, possibly through Mg²⁺ linkages.
• rRNA is present in the cytoplasm of both prokaryotic and eukaryotic cells.

• Messenger RNA (mRNA) is the most variable RNA in size and stability and is generally short-lived.
• It is single-stranded and has a primary structure complementary to a specific DNA segment.
• mRNA is formed by transcription, where uracil replaces thymine and ribose replaces deoxyribose.
• It carries genetic information from DNA to ribosomes and acts as a template for protein synthesis.
• mRNA may be monocistronic (coding for one protein) or polycistronic (coding for multiple proteins).

• Transfer RNA (tRNA) acts as an adapter molecule that transports specific amino acids to ribosomes during protein synthesis.
• It is a small RNA molecule of about 80 nucleotides and has a cloverleaf secondary structure and an inverted L-shaped tertiary structure.
• tRNA contains an anticodon that pairs with the complementary codon on mRNA.
• The 3′ end of tRNA has the sequence CCA, which serves as the amino acid attachment site.
• Each tRNA is charged with its specific amino acid by a specific enzyme called aminoacyl-tRNA synthetase.

• DNA replication is the process by which a DNA molecule makes exact copies of itself, each parental strand acting as a template for a new complementary strand, giving two identical daughter molecules with one old and one new strand each (semi-conservative).
• It occurs during the S-phase (Synthesis phase) of interphase in the cell cycle.
• Proposed by Watson and Crick (1953) and experimentally confirmed as semi-conservative by Meselson and Stahl (1958) in E. coli.
• Of the three proposed models, semi-conservative was proved correct, while conservative and dispersive were disproved.
• Replication is an autocatalytic function (DNA making DNA), unlike heterocatalytic functions, where DNA directs the synthesis of other molecules, like RNA (transcription) or protein (translation).

• The experiment was performed by Meselson and Stahl in 1958 using E. coli, which divides every 20 minutes and is easy to track across generations.
• Bacteria were grown in heavy nitrogen (¹⁵N) medium, then shifted to light nitrogen (¹⁴N) medium, and their DNA was separated by CsCl density gradient centrifugation.
• After the first replication, a single hybrid band appeared, which ruled out the conservative model.
• After the second replication, one hybrid and one light band appeared, which ruled out the dispersive model.
• These results proved that DNA replication is semi-conservative, where each new DNA molecule has one old strand and one new strand.

• Replication starts at the origin (ori), where helicase unwinds the helix into a replication fork, topoisomerase relieves supercoiling, and SSBPs keep the strands apart.
• Primase lays down a short RNA primer, giving DNA polymerase a free 3′-OH end to start adding nucleotides.
• The leading strand is made continuously (one primer); the lagging strand is made discontinuously as Okazaki fragments (many primers).
• DNA Pol I removes the primers and fills the gaps, and DNA ligase seals the nicks into a continuous strand.
• Termination occurs when forks meet at the Ter site (prokaryotes) or when replicons fuse (eukaryotes).

• Protein synthesis is the process by which cells produce proteins, which act as structural components, enzymes, and hormones.
• It involves two main steps: transcription (DNA → RNA) and translation (RNA → protein).
• In transcription, genetic information from DNA is copied into mRNA, where uracil (U) replaces thymine (T).
• Central dogma, proposed by Francis Crick (1958), states that information flows from DNA → RNA → protein.
• In retroviruses, reverse transcription occurs (RNA → DNA), explained by Temin and Baltimore (1970) using RNA-dependent DNA polymerase.

• Reverse transcription is the synthesis of complementary DNA (cDNA) from an RNA template by the enzyme reverse transcriptase (RNA-dependent DNA polymerase).
• It is also called Teminism, after Howard Temin, and occurs only in retroviruses.
• It contradicts the Central Dogma, since the flow here is RNA → DNA (not DNA → RNA).
• Discovered independently in 1970 by Temin and Baltimore in retroviruses.
• They won the 1975 Nobel Prize (with Dulbecco); it laid the foundation for retrovirology.

• Transcription is the process in which genetic information from one strand of DNA (template strand) is copied into RNA with the help of RNA polymerase.
• It occurs in the nucleoid in prokaryotes and in the nucleus in eukaryotes; mRNA then moves to the cytoplasm for translation.
• A transcription unit has three parts: promoter (start site), structural gene, and terminator (stop site).
• The process occurs in three stages: initiation (RNA polymerase binds promoter), elongation (RNA chain is formed), and termination (RNA polymerase detaches).
• Only one DNA strand acts as a template (3′→5′), while the other is the coding strand (5′→3′).
• In eukaryotes, primary RNA (hnRNA) is processed by capping, tailing, and splicing to form mature mRNA.

• Translation is the process by which the codon sequence on mRNA is decoded with the help of tRNA at the ribosome to form a specific sequence of amino acids in a protein.
• It needs mRNA (template), tRNA (adapter), ribosome (with A, P, and E sites), amino acids, aminoacyl-tRNA synthetase, ATP/GTP for energy, and Mg²⁺ ions.
• Before translation, amino acids are activated and linked to their specific tRNAs (charging) by aminoacyl-tRNA synthetase.
• Initiation: the small ribosomal subunit binds mRNA at the start codon (AUG), the initiator tRNA carrying methionine attaches, and the large subunit joins to form the initiation complex.
• Elongation: amino acids are added one by one through codon–anticodon pairing, peptide bonds form between them, and the ribosome moves forward by one codon at a time (translocation).
• Termination occurs at a stop codon (UAA, UAG, UGA), where release factors free the polypeptide and the ribosomal subunits separate.

• The genetic code is the coded information in the base sequence of DNA/mRNA that determines the amino acid sequence in a protein.
• It is a triplet code - three consecutive bases form one codon, proposed by George Gamow (1954).
• There are 64 codons in total: 61 code for amino acids and 3 are stop codons (UAA, UAG, UGA).
• AUG is the start codon and codes for methionine.
• It was deciphered mainly by Nirenberg, Khorana, and Ochoa (poly-U mRNA showed UUU = phenylalanine).
• It is degenerate (one amino acid can have several codons, usually differing in the third base - the wobble effect) and nearly universal.
• A change in the base sequence alters the amino acid sequence, so the code directly controls protein synthesis.

Prokaryote vs Eukaryote Packaging

• Gene regulation = switching genes ON or OFF based on the cell's requirement and stage of development.
• In eukaryotes, regulation occurs at 4 levels: Transcriptional (primary transcript), Processing (splicing), Transport (mRNA from nucleus to cytoplasm), and Translational.
• In prokaryotes, control of transcriptional initiation rate is the main site for gene expression control.
• E. coli produces β-galactosidase to break lactose → galactose + glucose. If lactose is absent, the enzyme is not produced, proving the environment regulates gene expression.
• Enzymes synthesized based on substrate availability are called inducible enzymes. The process = induction; the triggering molecule = inducer. This is a positive control.
• Feedback repression = when the end product (e.g., amino acid) is already available, genes for its production are switched OFF. This is a negative control.

• The operon concept (Jacob & Monod, 1961) explains how related genes are regulated together as one unit, based on the lac operon in E. coli.
• An operon has four parts: regulator (i), promoter (p), operator (o), and structural genes (z, y, a) - coding for β-galactosidase, permease, and transacetylase.
• The operator acts as an ON/OFF switch; when active, all three genes are transcribed into a single polycistronic mRNA (each gene = one cistron).
• The repressor (from the regulator gene) controls the operator - bound = OFF, unbound = ON.
• Inducible system (lac operon): the inducer (lactose) inactivates the repressor → transcription ON.
• Repressible system: a co-repressor activates the repressor → transcription OFF.

• The lac operon is an inducible operon in E. coli, proposed by Jacob and Monod (1961), that controls the metabolism of lactose.
• It consists of a regulator gene (i), promoter (P), operator (O), and three structural genes - lac z, lac y, lac a - coding for β-galactosidase, permease, and transacetylase respectively.
• When lactose is absent: the regulator gene produces an active repressor that binds the operator and blocks RNA polymerase, so the operon remains switched OFF.
• When lactose is present: lactose is converted into allolactose (the inducer), which binds the repressor and inactivates it, leaving the operator free.
• RNA polymerase then transcribes the structural genes into a single polycistronic mRNA, producing the enzymes that break down lactose - the operon is now switched ON.

• The Human Genome Project (HGP) was an international mega-project launched in 1990 and completed in 2003, coordinated mainly by the U.S. DOE and NIH.
• Its aim was to identify all human genes and sequence the entire human genome of about 3 billion base pairs.
• The main goals were to identify genes, sequence the genome, store the data, develop analysis tools, transfer technologies, and address ethical issues.
• Methodology: DNA was isolated, fragmented, cloned into vectors like BACs and YACs, sequenced by automated methods, and assembled using computers.
• Salient features: the genome has ~3 billion base pairs and 20,000–25,000 genes; less than 2% codes for proteins, and humans are 99.9% identical.
• Most genetic variation between individuals is due to SNPs (single-nucleotide polymorphisms).
• Applications: disease gene mapping, early diagnosis, personalised medicine, evolutionary studies, and advances in biotechnology.
• ELSI (Ethical, Legal, Social Issues): genome data must be kept confidential to prevent misuse and discrimination.

• DNA fingerprinting is a technique used to identify an individual by analysing the unique DNA pattern present in every person (except identical twins).
• It is based on satellite DNA, especially VNTRs (Variable Number Tandem Repeats) - short sequences repeated in tandem, whose number varies among individuals and creates DNA polymorphism.
• Principle: the differences in VNTR repeat number produce DNA fragments of different lengths, which appear as a unique banding pattern.
• Steps: DNA isolation → PCR amplification → restriction digestion → gel electrophoresis → Southern blotting → probe hybridisation → autoradiography → comparison of band patterns.
• Applications: forensic identification, paternity/maternity testing, pedigree studies, medical research, conservation biology, and evolutionary/anthropological studies.

• The Rice Genome Project was initiated because rice (Oryza sativa) is a major global food crop and has the smallest genome among major cereals (400–430 Mb).
• The International Rice Genome Sequencing Project (IRGSP) began in 1997 as a multinational collaboration involving 11 countries, including Japan, India, China, the USA, and the UK.
• The rice genome was sequenced mainly using the shotgun sequencing approach with BAC and PAC clones.
• The rice genome is estimated to contain about 37,500 genes, with nearly 50% consisting of repetitive DNA.
• Sequencing rice genome provides insights into genome organization and helps in understanding cereal crop genetics.
• Knowledge from the rice genome aids in developing improved rice varieties with high yield, disease resistance, and stress tolerance through modern breeding techniques.