DNA: The Molecule of Heredity – Discovery and Structure

Posted on Dec 1, 2024 in Biology

Biomolecules and Heredity

Biomolecules are substances closely related to life processes. Carbohydrates, lipids, and proteins are metabolized to produce energy and cellular materials. A fourth biomolecule, nucleic acids, is not processed for energy but is crucial for transmitting hereditary traits and protein synthesis. Nucleic acids include deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is primarily found in the nucleus, with small amounts in mitochondria and chloroplasts. 80% of RNA is in ribosomes.

During cell division, chromatin condenses into chromosomes (Fig. 2). Human cells have 23 pairs of chromosomes. Each chromosome consists of two chromatids joined at the kinetochore. DNA within chromosomes forms units called genes. Humans have approximately 26,383 to 39,114 genes, according to the Human Genome Project.

Condensation of Chromatin, Chromosomes, and Genes

A significant challenge in molecular biology was determining DNA’s structure, as it carries genetic information. The discovery of the double helix explained how genetic information is stored, duplicated, and transmitted. A key question was: How was it discovered that DNA was the material of heredity?

The DNA: Material of Heredity

The journey began with Friedrich Miescher, a German physician who isolated nuclein from white blood cells and salmon sperm in 1869. Later, nuclein was found to comprise proteins and nucleic acids (deoxyribonucleic acid or DNA and ribonucleic acid or RNA). In 1880, Wilhelm Roux proposed that genetic information is stored on chromosomes. Oscar Hertwing (1884) suggested that chromatin was responsible for hereditary traits. In 1914, Robert Feulgen used fuchsin dye to stain DNA, finding it in all eukaryotic cell nuclei, especially chromosomes. Animal and plant chromosomes are complex structures: 27% DNA, 66% protein, and 6% RNA (Fig. 3).

Chemical Composition of Chromosomes

Miescher’s discovery and subsequent contributions by Roux and Feulgen initiated the search for the hereditary material. The prevailing ideas were:

• Chromosomes are associated with heredity.
• Chromosomes contain proteins, DNA, and RNA.
• The hereditary substance must self-replicate and be transmitted to offspring.

The link between DNA and inheritance required contributions from researchers like Fred Griffith, Oswald Avery et al., Phoebus Aaron Levene, Erwin Chargaff, Alfred D. Hershey and Martha Chase, James Watson and Francis Crick, and Matthew Meselson and Franklin W. Stahl.

Phoebus Aaron Levene

In 1920, Levene established that DNA consists of four nitrogenous bases (adenine, guanine, cytosine, and thymine), a deoxyribose sugar molecule, and a phosphate group.

Fred Griffith

Griffith’s work with pneumococcal bacteria, which cause pneumonia, was pivotal. There are two strains: smooth (S), which has a capsule and causes pneumonia (Fig. 4), and rough (R), which lacks a capsule and doesn’t cause disease. In 1928, Griffith found that non-pathogenic R pneumococci could become pathogenic S pneumococci. His experiments showed:

• Live S pneumococci injected into mice caused death; live S pneumococci were found in the blood.
• Live R pneumococci injected into mice did not cause illness; live R pneumococci were found in the blood.
• Heat-killed S pneumococci injected into mice did not cause illness; dead S pneumococci were found in the blood.
• A mixture of live R and heat-killed S pneumococci caused death; live S pneumococci were found in the blood.

Non-pathogenic R pneumococci were transformed into pathogenic S pneumococci.

Avery, MacLeod, and McCarty

In 1944, Avery, MacLeod, and McCarty fractionated S pneumococci extracts and added each component to R pneumococci cultures. Transformation occurred only when the DNA fraction was added, concluding that DNA was the transforming principle and the material of heredity. This was the first experimental link between inheritance and a chemical molecule.

Erwin Chargaff

Between 1949 and 1951, Chargaff analyzed the nitrogenous base composition of DNA from various sources. He concluded:

• In all DNA, adenine equals thymine (A=T) and guanine equals cytosine (G=C).
• DNA from different tissues of the same species has the same base composition.
• Base composition varies between species.
• DNA composition does not change with age or nutrition.

James Watson and Francis Crick

In 1953, Watson and Crick proposed the double helix model for DNA structure, based on Rosalind Franklin and Maurice Wilkins’ X-ray crystallography and Chargaff’s rules. They also explained DNA replication and its role in the genetic code.

Three-dimensional Structure of DNA

Alfred Hershey and Martha Chase

In 1952, Hershey and Chase confirmed DNA’s genetic role using the T₂ bacteriophage, which infects E. coli bacteria (Fig. 6). The bacteriophage injects its genetic material, causing the bacteria to produce new viruses. Using radioactive labeling, they showed that the injected DNA, not protein, caused the changes in the bacteria (Fig. 7).

Reproductive Cycle of Bacteriophage T₂

Representation of Alfred Hershey and Martha Chase’s Experiment in Bacteriophage T₂

Nucleic Acids

Nucleic acids carry genetic information across generations, as demonstrated by Avery, MacLeod, and McCarty in 1944. Levene and Chargaff elucidated their chemical composition.

Nucleotides

Levene showed that the structural unit of nucleic acids is the nucleotide, composed of:

a) A nitrogenous base (purine or pyrimidine)

Nitrogenous Bases in Nucleic Acid Structure

b) A 5-carbon sugar molecule (ribose or deoxyribose)

Ribose and Deoxyribose

c) A phosphate group

Phosphate Group

The phosphate group and nitrogenous base attach to the sugar molecule. The phosphate group binds to the sugar’s carbon 5, and the nitrogenous base binds to carbon 1 (Fig. 8). Nucleotides are named based on their nitrogenous base: thymine, adenine, guanine, cytosine, and uracil.

Nucleotides of Adenine and Thymine

Polynucleotides

Nucleic acids are formed by linking nucleotides into polynucleotides. Nucleotides bind via the OH group of carbon 3 of one sugar molecule and the phosphate-OH group attached to carbon 5 of the next sugar molecule (Fig. 9). DNA and RNA are polynucleotides with the following components:

Representation of a Polynucleotide

Chemical Components of Nucleic Acids