The genetic information of an organism is stored in the form of nucleic acids. Nucleic acids, DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), are long linear polymers composed of nucleotide building blocks. Each nucleotide is comprised of a sugar, a phosphate residue, and a nitrogenous bases (a purine or pyrimidine). DNA is longer than RNA and contains the entire genetic information of an organism encoded in the sequences of the bases. In contrast, RNA only contains a portion of the information and can have completely different functions in the cell.
DNA is structurally characterized by its double helix: two opposite, complementary, nucleic acids strands that spiral around one another. The DNA backbone, with alternatively linked sugar and phosphate residues, is located on the outside. The bases are located inside the helix and form the base pairs adenine and thymine or guanine and cytosine, which are linked by hydrogen bonds.
The human genome comprises 3.2 x 109 base pairs, which are distributed over 23 pairs of chromosomes. Each chromosome is a linear DNA molecule of a certain length. The chromosome is only well visualized under the light microscope during the metaphase of mitosis, as it is maximally condensed during this phase. Chromosomes are present as pairs in most cells of the body. One chromosome in each of the 23 pairs originates from the mother and the other from the father.
Both interrelated chromosomes are termed homologous because they each have a variant of the same gene. Alterations in the number or structure of the chromosomes lead to various conditions, e.g., developmental disorders. Chromosomal assessment with different molecular biology and cytogenetic methods often allows for a clear diagnosis.
- See learning card on for more details.
|Rings||Base||Notable characteristics||As a nucleoside unit in RNA||As a nucleoside unit in DNA|
|Pyrimidines|| ||Cytosine (C)|| || |
|Thymine (T)|| || |
|Uracil (U)|| |
|Purines|| ||Adenine (A)|| || || |
|Guanine (G)|| |
CUT the PYrimidine;PURine As Gold.
- Other than uracil, there are many other bases that may be created after the initial nucleic acid chain formation, for example:
Amino acids required for purine synthesis
A MEAN person GAGs a PURring cat!
Nucleic acid sugars
- Structure: The sugar found in nucleic acids is a pentose, which has a five-atom ring. Specifically, the sugar in:
- Bases via N-glycosidic bonds
- Phosphate residue via phosphodiester bonds
- A nucleotide can have one, two, or three phosphate groups (also termed “nucleoside monophosphate”, “diphosphate”, and “triphosphate”, respectively).
- Nucleic acids are composed of nucleoside monophosphates.
- Nucleoside diphosphates and nucleoside triphosphates (e.g., ATP) are found in biochemical processes requiring energy.
- Building blocks of nucleic acids
- Source of energy: : especially as a universal energy carrier of the cell in the form of ATP, but also GTP
- Signal molecules: especially the second messenger cAMP (cyclic adenosine monophosphate) and cGMP (cyclic guanosine monophosphate) , both phosphoric esters
Activators for the transfer of groups: Through the potential of forming energy-rich bonds, nucleotides are able to transfer a molecule onto another in biosynthesis, e.g.:
- UDP-Glucose is an active form of glucose in gluconeogenesis.
- Dietary choline can be activated to citicoline by CTP and be used in the synthesis of phosphatidylcholine.
- 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) serves as a sulfate group donor in sulfatide synthesis.
- S-Adenosyl methionine (SAM) is formed from methionine and serves as a cofactor in methylation reactions.
- Regulators: enzyme reactions in signal transduction pathways (e.g., activates GTP G proteins)
- Carrier molecules: e.g., the electron carrier nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) as a component of coenzymes in redox reactions
The energy carrier ATP contains ribose and not deoxyribose as a sugar, and therefore has a 2' OH group!
- Long, linear chains (polymers) of nucleotides
- Alternating sugar and phosphate residues of individual nucleotides, linked by phosphodiester bonds, form the backbone
- Primary structure of nucleic acids: nucleotide sequence in the chain
- Phosphodiester bonds are negatively charged.
- Negative charges stabilize the nucleic acids.
- Phosphodiester bonds cannot be easily hydrolyzed like other esters.
- The chemical composition of nucleic acids (DNA and RNA) and their structure of repetitive nucleotide units allow them to function as both information carrier and mediator.
|Sugar|| || |
|Length|| || |
|Function|| || |
Overview of DNA structure and packaging
- Organization of the human genome: Nucleotides form single-stranded DNA → stabilizes into double-stranded DNA → conforms into right-handed double helix → chromatin formation begins when the double helix binds histone to form nucleosomes (appear as “beads on a string” under electron microscopy) → chromatin is further compacted → during replication (mitosis or meiosis), chromatin maximally condenses into chromosomes (only visible during metaphase under light microscopy)
- DNA is very flexible in the longitudinal direction. DNA conformation can be affected by protein binding. The sequence of bases also has an effect on the local structure.
- DNA is primarily a double-stranded chain of deoxyribonucleotides in cells
- Both strands are complementary to each other and run anti-parallel .
Double helix: 3D structure of DNA in which two polynucleotide strands are intertwined
- Stabilized by:
- Specific base pairing via hydrogen bonds (H bonds) between complementary nucleobases of DNA
- Hydrophobic effect: The negatively charged is located on the outside of the helix, the bases on the inside.
- Base stacking: The base pairs are stacked on one another (stacking interactions) and interact through , which have an additional stabilizing effect.
- The double helix of DNA has a minor groove and a major groove.
- There are 3 DNA conformations (A-DNA, B-DNA, Z-DNA): The DNA present in cells is usually B-DNA and is, therefore, a right-handed double helix.
- B conformation (B-DNA): most prevalent
- A conformation (A-DNA)
- Z conformation (Z-DNA)
- Stabilized by:
Further structural characteristics of DNA
- Definition: winded double helix , also termed “superhelix”
- Occurrence: especially in circular DNA molecules
- Characteristics: Supercoiled DNA molecules have a more compact structure than the relaxed form of DNA.
- Definition: A palindrome is a sequence that reads the same forwards and backward, e.g., Otto
- The molecular biological use of the term “palindrome” is for inverted repeats (repeated sequence in the opposite direction).
- In DNA, a palindrome is a sequence of base pairs that reads the same on two strands when the orientation of reading is kept the same. For example, the following sequences read the same on the two strands in 5'→3' direction.
- In palindromic sequences, a sequence of base pairs occurring over a certain segment is read identically on both complementary DNA strands, i.e., the sequence always reads the same on both strands in a 5'→3' direction.
- Bases may be present between the palindromic sequences that are not complementary.
- These segments are self-complementary and can form a hairpin loop.
- Results in the formation of a cross-shaped structure in double-stranded DNA
- Function: Some proteins that are capable of binding DNA require palindromic sequences as a recognition sequence, e.g., steroid hormone receptors or restriction enzymes.
- Definition: complex of DNA and its associated proteins (both histones and non-histones) structured as repetitive units (nucleosomes)
- Function: condensation and organization of DNA structure (also influences gene regulation)
- Contains inactive DNA because the highly condensed, steric conformation does not allow transcription
- Darker on electron microscopy (EM)
- DNA methylation is ↑ and acetylation is ↓
- Constitutive heterochromatin: especially from noncoding, repetitive DNA sequences, which is also present in a condensed form in the nucleus during interphase and especially located close to the telomere and centromere
- Facultative heterochromatin: coding, i.e., gene-containing DNA sequences that may be facultative, i.e., optional, present as heterochromatin but also unpacked as euchromatin
Components of chromatin
- Definition: group of proteins that bind to DNA in the nucleus of eukaryotes to support the structure of chromatin
Types: There are four core histones and a linker.
4 Core histones: H2A, H2B, H3, H4
- All four core histones have a similar structure that has hardly changed during the course of evolution (highly conserved).
- 2 molecules of each core histone form; the nucleosome 8-protein complex core, a histone octamer, around which the DNA is wound in segments
- Controls gene expression via reversible post-translation modification of histones (acetylation, methylation, phosphorylation, ubiquitinylation, Sumoylation, ADP-ribosylation)
- Linker histone = H1
- 4 Core histones: H2A, H2B, H3, H4
Nucleosome (nucleosome core particle)
- Definition: : A structural and functional complex of DNA (∼ 150 bp)and histone octamer that gives chromatin its “beads on a string” appearance
- DNA wraps ; and forms a flat, left-handed superhelix around the nucleosome core with ∼ 1.8 twists
- Nucleosomes are linked to one another through short DNA segment of variable lengths (average 50–60 bp)
See the “Basics of human genetics” for more information.
- A denser packaging of chromatin that only becomes visible under microscope during cell division (especially in metaphase)
- Number of chromosomes in the human genome:
- Structure: A chromosome pair consists of 2 identical chromatids connected at the center by a centromere.
- The human genome consists of ∼ 3.2 billion base pairs (bp).
- The DNA stored in a human cell would total ∼ 1.8 m in length.
- In addition to the nuclear genome (found in the nucleus), there is also a mitochondrial genome that largely codes for RNA-associated proteins
- ∼ 10% contains genes and related sequences
∼ 90% does not contain genes
- The function of ∼ 50% of DNA sequences is unknown.
∼ 45% is composed of repetitive sequences (repetitive genetic elements).
- Simple repetitive DNA elements (tandem repeats)
- Previously mobile genetic elements (such as , LTR , non-LTR, LINE , SINE )
- ∼ 24% of the genome is spanned by introns.
RNA classes and their structure
RNAs can be differentiated into various types, which differ in their length, structure, and function. Depending on the type, RNA can be a single-stranded or double-stranded segment.
|Classification of RNA|
|mRNA (messenger RNA)|| |
|tRNA (transfer RNA)|| |
|rRNA (ribosomal RNA)|
|snRNA (small nuclear RNA|| |
|snoRNA (small nucleolar RNA)|| |
RNA component of signal recognition particles |
or scRNA (small cytoplasmic RNA)
|Telomerase RNA component (human telomerase RNA, hTR)|| |
|miRNA (microRNA)|| || |
|siRNA (small interfering RNA)|