Nucleic acids are information-carrying molecules composed of nucleotide monomers, and they function in the storage, transmission, and expression of genetic information in cells.
Nucleic Acids and Their Central Role
Nucleic acids are essential macromolecules found in all living organisms. They store and transmit hereditary information that determines an organism’s traits and direct the synthesis of proteins, which are responsible for cellular structure and function. The two main types of nucleic acids are DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).
Both are composed of nucleotides—small repeating units that link to form long chains. These chains form the molecular basis of heredity and are critical for gene expression. The unique sequences and structural properties of nucleic acids make them well-suited to their biological roles.
Image courtesy of Wikimedia Commons.
Nucleotide Composition and Structure
Each nucleotide has three components:
A five-carbon sugar: deoxyribose in DNA, ribose in RNA
A phosphate group: links one nucleotide to the next
A nitrogenous base: the information-coding component
The nitrogenous bases are classified as either:
Purines: adenine (A) and guanine (G) – double-ring structures
Pyrimidines: cytosine (C), thymine (T), and uracil (U) – single-ring structures
Image courtesy of EpoMedicine
DNA includes A, T, G, and C.
RNA includes A, U, G, and C.
The nucleotides are joined by phosphodiester bonds, forming a sugar-phosphate backbone, with bases extending inward or outward depending on whether the molecule is double- or single-stranded.
Structure and Directionality
Nucleic acids have directionality, meaning one end is chemically distinct from the other:
The 5' end contains a free phosphate group attached to the fifth carbon of the sugar.
The 3' end has a free hydroxyl group on the third carbon.
Nucleotide polymers are always assembled 5' to 3', and this orientation determines how enzymes interact with the strands during replication and transcription.
In double-stranded DNA, the two strands run in opposite directions, known as antiparallel orientation. One strand runs 5’ to 3’, and the other 3’ to 5’. This configuration is crucial for base pairing and the accurate copying of genetic material.
DNA: Storage and Transfer of Genetic Information
DNA stores genetic information in the form of base sequences, which serve as instructions for building proteins. The molecule is shaped like a double helix—two strands twisted around each other.
Base pairing rules (Chargaff’s Rule):
Adenine (A) pairs with Thymine (T) using two hydrogen bonds
Guanine (G) pairs with Cytosine (C) using three hydrogen bonds
These hydrogen bonds stabilize the DNA molecule and ensure complementarity. When DNA replicates, each strand serves as a template for creating a complementary strand.
DNA Replication
Helicase unwinds the DNA helix.
DNA polymerase adds complementary nucleotides to each strand.
New strands are synthesized in the 5' to 3' direction.
Replication is semi-conservative, meaning each new DNA molecule contains one original strand and one newly synthesized strand.
DNA Packaging
In eukaryotic cells, DNA wraps around histone proteins to form nucleosomes, which coil and fold into chromatin. Further folding creates chromosomes.
Tightly packed DNA (heterochromatin) is transcriptionally inactive.
Loosely packed DNA (euchromatin) is accessible for gene expression.
This organization helps fit DNA into the nucleus and regulates gene accessibility.
RNA: Expression and Translation of Genetic Information
RNA is generally single-stranded and plays diverse roles in gene expression and regulation. While it shares structural similarities with DNA, it differs in several key ways:
Contains ribose sugar (has an –OH group at the 2' carbon)
Uses uracil (U) instead of thymine
Typically single-stranded, but can form folded structures
Types of RNA and Their Functions
mRNA (messenger RNA): Carries genetic code from DNA to ribosomes
tRNA (transfer RNA): Brings amino acids to the ribosome and pairs with mRNA codons using its anticodon
rRNA (ribosomal RNA): Forms part of the ribosome’s structure and catalyzes peptide bond formation
snRNA (small nuclear RNA): Participates in RNA splicing
miRNA (microRNA): Involved in gene regulation
Each RNA type has a structure tailored to its role, with folded regions stabilized by internal base pairing.
Base Pairing and Complementarity
Complementary base pairing ensures:
Replication accuracy: Bases pair specifically (A-T or A-U, G-C)
Transcription fidelity: mRNA reflects the DNA coding sequence
Stability: Hydrogen bonds maintain the structure of DNA and RNA folds
The specific base pairing between nucleotides is essential for the continuity and regulation of genetic information.
Encoding Genetic Information
DNA stores information in the sequence of its bases, which is read as codons—groups of three bases—during protein synthesis. Each codon corresponds to one amino acid or a start/stop signal in translation.
Start codon: AUG (methionine)
Stop codons: UAA, UAG, UGA
The genetic code is:
Universal: Found in nearly all organisms
Redundant: Multiple codons can specify the same amino acid
Non-overlapping and unambiguous
These features ensure that protein synthesis is accurate and efficient.
From DNA to Protein: The Central Dogma
The central dogma of molecular biology describes the flow of genetic information:
Replication: DNA copies itself before cell division.
Transcription: DNA is used as a template to make mRNA.
Translation: mRNA is decoded by ribosomes to build a protein.
Transcription
Occurs in the nucleus of eukaryotic cells.
RNA polymerase reads the DNA template strand 3' to 5'.
A complementary mRNA strand is synthesized 5' to 3'.
Translation
Occurs in the cytoplasm at the ribosome.
tRNA matches its anticodon to mRNA codons and brings in amino acids.
The ribosome links amino acids with peptide bonds, forming a polypeptide chain.
RNA Folding and Catalysis
RNA, although single-stranded, can form complex shapes:
Hairpin loops
Stem-loops
Pseudoknots
These structures are stabilized by intramolecular base pairing and allow RNA to:
Catalyze reactions (ribozymes)
Bind other molecules
Control gene expression
An example is the ribosome’s peptidyl transferase center, which is made entirely of rRNA and catalyzes peptide bond formation.
Genetic Mutations and Their Impact
Changes in the nucleotide sequence are known as mutations, which can affect gene expression and protein function:
Silent mutation: No change in protein
Missense mutation: One amino acid is changed (may affect function)
Nonsense mutation: Early stop codon leads to truncated protein
Frameshift mutation: Insertion or deletion shifts reading frame
Mutations can be caused by:
Errors in replication
Radiation
Chemicals
Some mutations are harmful, while others provide genetic variation, which drives evolution.
Base Composition and Thermal Stability
The proportion of guanine (G) and cytosine (C) bases influences DNA’s thermal stability:
G-C pairs form three hydrogen bonds, making them stronger than A-T pairs (which form two).
DNA with higher G-C content requires more energy (higher temperature) to denature.
This property is important in molecular biology techniques like PCR (polymerase chain reaction) and in understanding species differences in genome composition.
Quantitative Example Using Chargaff’s Rule
If a DNA sample has 20% adenine:
Then it has 20% thymine (A = T)
The remaining 60% is divided between guanine and cytosine
So, guanine = 30% and cytosine = 30%
Knowing one base’s percentage allows you to calculate the others, which is useful in DNA analysis and species identification.
Summary of Key Differences Between DNA and RNA
Sugar: DNA has deoxyribose; RNA has ribose
Strands: DNA is double-stranded; RNA is usually single-stranded
Bases: DNA uses thymine; RNA uses uracil
Function: DNA stores genetic info; RNA transfers and expresses it
Stability: DNA is more stable; RNA is more reactive due to the 2' hydroxyl
These differences enable the two molecules to specialize—DNA for stable information storage, RNA for dynamic information expression.
FAQ
RNA’s ability to fold into secondary structures such as hairpins, loops, and bulges is essential for its function beyond coding. These structures are formed through intramolecular base pairing between complementary regions within the RNA strand and allow RNA to adopt three-dimensional conformations necessary for its roles in cells.
In tRNA, cloverleaf-shaped folding positions the anticodon and amino acid attachment site for accurate translation.
In rRNA, complex folds stabilize ribosome structure and catalyze peptide bond formation.
Regulatory RNAs use these shapes to bind proteins or other RNAs, influencing gene expression.
Thus, structure directly enables RNA’s functional diversity.
The sugar-phosphate backbone provides structural integrity and orientation for nucleic acids. It consists of alternating five-carbon sugars and phosphate groups connected by phosphodiester bonds, creating a strong, polar, and negatively charged framework.
This backbone protects the nitrogenous bases on the interior (especially in DNA).
Its polarity (5’ to 3’ directionality) is essential for enzyme recognition and synthesis processes.
The negative charge helps repel nucleophiles, increasing chemical stability.
It enables the DNA double helix to twist uniformly and provides rigidity in RNA for folded structures.
Without this backbone, nucleic acids wouldn’t have the stability or shape necessary for reliable information storage and transfer.
The distinction between 5’ and 3’ ends is fundamental for replication, transcription, and translation. DNA and RNA polymerases can only add nucleotides to the 3’ hydroxyl group of a growing strand, ensuring unidirectional synthesis.
During DNA replication, the leading strand is synthesized continuously 5’ to 3’, while the lagging strand is synthesized in Okazaki fragments.
In transcription, RNA polymerase reads the DNA template 3’ to 5’ and synthesizes RNA 5’ to 3’.
mRNA is translated starting at its 5’ cap, and the ribosome reads codons from 5’ to 3’.
Maintaining proper orientation ensures correct sequence copying and processing.
In eukaryotic cells, mRNA must be processed before translation to ensure stability and accurate protein production. These modifications occur after transcription and are linked to the linear structure and directionality of RNA.
5’ capping: A modified guanine is added to the 5’ end, protecting the mRNA from degradation and helping ribosome binding.
3’ poly-A tail: A stretch of adenine nucleotides is added to the 3’ end, enhancing stability and export from the nucleus.
Splicing: Introns (non-coding regions) are removed, and exons (coding regions) are joined.
These structural changes rely on precise recognition of nucleotide sequences and maintain the correct reading frame during translation.
The nucleotide composition, particularly the ratio of G-C to A-T base pairs, influences the DNA molecule’s melting temperature (Tm)—the point at which the two strands separate.
G-C pairs have three hydrogen bonds and are stronger than A-T pairs, which have two.
DNA with higher G-C content has a higher Tm and requires more heat to denature.
In PCR (polymerase chain reaction), primers with balanced G-C content and optimal Tm improve binding efficiency and amplification accuracy.
Researchers calculate Tm to set appropriate annealing temperatures, which prevent non-specific binding.
Understanding base composition helps optimize molecular biology techniques and ensures accurate DNA amplification.
Practice Questions
Describe how the structural differences between DNA and RNA contribute to their distinct biological functions.
DNA and RNA differ in sugar type, strand structure, and nitrogenous bases, and these differences support their roles. DNA contains deoxyribose, making it more chemically stable for long-term genetic storage. Its double-stranded, antiparallel helix provides protection for bases and allows accurate replication. DNA uses thymine, which resists degradation better than uracil. In contrast, RNA contains ribose, making it more reactive and suitable for short-term roles. RNA is typically single-stranded and folds into various shapes, allowing it to function as mRNA, tRNA, or rRNA. RNA uses uracil, which is energetically easier to produce, fitting its temporary, regulatory role in gene expression.
Explain how complementary base pairing allows DNA to replicate accurately. Include the roles of hydrogen bonds and directionality.
Complementary base pairing ensures accurate DNA replication by allowing each strand to serve as a template. Adenine pairs with thymine via two hydrogen bonds, and guanine pairs with cytosine via three hydrogen bonds, maintaining uniform helix width and stability. During replication, enzymes like helicase unwind the double helix, and DNA polymerase adds nucleotides to the 3' end of a new strand, using the original strand’s 5' to 3' template. Because of directionality and specific pairing rules, the sequence of the new strand exactly complements the template, minimizing errors and ensuring faithful transmission of genetic information during cell division.
