Nucleic Acids and the Genetic Code: Structure, Function, and Mutations

Nucleic Acids: Structure and Function

Types of Nucleic Acids

Nucleic acids are polymeric macromolecules essential for the storage and transmission of genetic information. The two main types are DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).

• DNA: Carrier of genetic information, found in chromosomes.

• RNA: Functions as an intermediate in gene expression and has diverse roles; not found in chromosomes.

Nucleotides: Building Blocks of Nucleic Acids

Nucleotides are the monomeric units of nucleic acids, each composed of:

• A pentose sugar (ribose in RNA, deoxyribose in DNA)

• A nitrogenous base (adenine, guanine, cytosine, thymine in DNA; uracil replaces thymine in RNA)

• A phosphate group

The chemical linkage between nucleotides is a phosphodiester bond.

Primary Structure of DNA

The primary structure of DNA is defined by its sequence of nucleotides. Erwin Chargaff's rules state:

• The amount of adenine (A) is proportional to thymine (T).

• The amount of cytosine (C) is proportional to guanine (G).

• Base pairing: A-T (or T-A), G-C (or C-G).

Double Helix and Antiparallel Strands

DNA consists of two polynucleotide chains wound into a right-handed double helix. Key features include:

• Sugar-phosphate backbone on the outside, bases on the inside.

• Strands are held together by hydrogen bonds between bases.

• The two strands are antiparallel: one runs 5'→3', the other 3'→5'.

Functions of DNA

• Transmission of genetic information to progeny.

• Template for synthesis of proteins in cells.

Types of RNA

RNA molecules play various roles in gene expression and regulation:

Type	Function
mRNA	Encodes proteins
tRNA	Adaptor between mRNA and amino acids
rRNA	Forms the ribosome
snRNA	Functions in nuclear processes
snoRNA	Facilitates chemical modification of RNAs
miRNA	Regulates gene expression
siRNA	Silences gene expression
lncRNA	Regulates gene expression

Central Dogma of Molecular Biology

Flow of Genetic Information

The central dogma describes the process by which genetic information is transferred from DNA to RNA to protein:

• Transcription: DNA is transcribed into RNA.

• Translation: RNA is translated into protein.

The Genetic Code

Codons and Their Role

A codon is a sequence of three adjacent nucleotides in mRNA that specifies an amino acid or a stop signal during protein synthesis.

• There are 20 different amino acids and 64 possible codons ($4^3 = 64$).

• The genetic code is interpreted by the cell to synthesize proteins.

Characteristics of the Genetic Code

• The code is a triplet code: three nucleotides per codon.

• Codons are successive and non-overlapping.

• The code is nearly universal across organisms.

• The code is degenerate: multiple codons can specify the same amino acid.

• AUG is the start codon; UAG, UAA, and UGA are stop codons.

Codon Table

First Nucleotide	Second Nucleotide	Third Nucleotide	Amino Acid
U	U	U	Phe
A	U	G	Met (Start)
U	A	A	Stop
U	G	A	Stop
C	G	G	Arg

Transcription and Translation

Transcription

Transcription is the synthesis of RNA from a DNA template. The antisense strand of DNA serves as the template for mRNA synthesis.

• Example: For DNA sequence 5'-AGCTTAAGGCTTA-3' (sense), the template is 3'-TCGAATTCCGAAT-5'.

• The mRNA sequence (5'→3') is: AGCUUAAGGCUUA

Translation

Translation is the process by which ribosomes synthesize proteins using the sequence of codons in mRNA.

• tRNA molecules bring amino acids to the ribosome, matching their anticodon to the mRNA codon.

• Protein synthesis proceeds from the start codon to a stop codon.

Reading Frames

Without a specified start, a nucleotide sequence can be read in three possible reading frames, each producing a different amino acid sequence.

Effect of Mutations on mRNA and Protein Synthesis

Types of Mutations

• Missense mutations: Replace one amino acid with another; effects vary from benign to severe (e.g., sickle cell anemia).

• Nonsense mutations: Introduce a premature stop codon, usually causing loss of function.

• Frameshift mutations: Insertions or deletions that alter the reading frame, often with severe consequences.

• Not all base substitutions change the encoded amino acid (synonymous vs. nonsynonymous substitutions).

Examples

• ACU → AGU: nonsynonymous substitution (Thr → Ser)

• ACU → ACC: synonymous substitution (Thr → Thr)

Short-hand Names for Amino Acids

Amino Acid	3-Letter Code	1-Letter Code
Alanine	Ala	A
Cysteine	Cys	C
Aspartic Acid	Asp	D
Glutamic Acid	Glu	E
Phenylalanine	Phe	F
Glycine	Gly	G
Histidine	His	H
Isoleucine	Ile	I
Lysine	Lys	K
Leucine	Leu	L
Methionine	Met	M
Asparagine	Asn	N
Proline	Pro	P
Glutamine	Gln	Q
Arginine	Arg	R
Serine	Ser	S
Threonine	Thr	T
Valine	Val	V
Tryptophan	Trp	W
Tyrosine	Tyr	Y

Key Equations and Concepts

• Number of possible codons: $4^3 = 64$

• Base pairing: $A = T$, $C = G$

• Directionality: DNA and RNA are synthesized in the 5'→3' direction.

Additional info: These notes expand on the lecture slides and images to provide a comprehensive overview suitable for Organic Chemistry students studying nucleic acids and the genetic code.