Molecular genetics

Molecular genetics is a branch of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the structure and/or function of genes in an organism's genome using genetic screens. 

The field of study is based on the merging of several sub-fields in biology: classical Mendelian inheritance, cellular biology, molecular biology, biochemistry, and biotechnology. It integrates these disciplines to explore things like genetic inheritance, gene regulation and expression, and the molecular mechanism behind various life processes.

A key goal of molecular genetics is to identify and study genetic mutations. Researchers search for mutations in a gene or induce mutations in a gene to link a gene sequence to a specific phenotype. Therefore molecular genetics is a powerful methodology for linking mutations to genetic conditions that may aid the search for treatments of various genetics diseases.

The discovery of DNA as the blueprint for life and breakthroughs in molecular genetics research came from the combined works of many scientists. In 1869, chemist Johann Friedrich Miescher, who was researching the composition of white blood cells, discovered and isolated a new molecule that he named nuclein from the cell nucleus, which would ultimately be the first discovery of the molecule DNA that was later determined to be the molecular basis of life. He determined it was composed of hydrogen, oxygen, nitrogen and phosphorus. Biochemist Albrecht Kossel identified nuclein as a nucleic acid and provided its name deoxyribonucleic acid (DNA). He continued to build on that by isolating the basic building blocks of DNA and RNA; made up of the nucleotides: adenine, guanine, thymine, cytosine. and uracil. His work on nucleotides earned him a Nobel Prize in Physiology.

In the early 1800s, Gregor Mendel, who became known as one of the fathers of genetics, made great contributions to the field of genetics through his various experiments with pea plants where he was able to discover the principles of inheritance such as recessive and dominant traits, without knowing what genes where composed of. In the mid 19th century, anatomist Walther Flemming, discovered what we now know as chromosomes and the separation process they undergo through mitosis. His work along with Theodor Boveri first came up with the Chromosomal Theory of Inheritance, which helped explain some of the patterns Mendel had observed much earlier.

For molecular genetics to develop as a discipline, several scientific discoveries were necessary.  The discovery of DNA as a means to transfer the genetic code of life from one cell to another and between generations was essential for identifying the molecule responsible for heredity. Molecular genetics arose initially from studies involving genetic transformation in bacteria. In 1944 Avery, McLeod and McCarthy isolated DNA from a virulent strain of S. pneumoniae, and using just this DNA were able to convert a harmless strain to virulence. They called the uptake, incorporation and expression of DNA by bacteria "transformation". This finding suggested that DNA is the genetic material of bacteria. Bacterial transformation is often induced by conditions of stress, and the function of transformation appears to be repair of genomic damage.

In 1950, Erwin Chargaff derived rules that offered evidence of DNA being the genetic material of life. These were "1) that the base composition of DNA varies between species and 2) in natural DNA molecules, the amount of adenine (A) is equal to the amount of thymine (T), and the amount of guanine (G) is equal to the amount of cytosine (C)." These rules, known as Chargaff's rules, helped to understand of molecular genetics. In 1953 Francis Crick and James Watson, building upon the X-ray crystallography work done by Rosalind Franklin and Maurice Wilkins, were able to derive the 3-D double helix structure of DNA.

The phage group was an informal network of biologists centered on Max Delbrück that contributed substantially to molecular genetics and the origins of molecular biology during the period from about 1945 to 1970. The phage group took its name from bacteriophages, the bacteria-infecting viruses that the group used as experimental model organisms. Studies by molecular geneticists affiliated with this group contributed to understanding how gene-encoded proteins function in DNA replication, DNA repair and DNA recombination, and on how viruses are assembled from protein and nucleic acid components (molecular morphogenesis). Furthermore, the role of chain terminating codons was elucidated. One noteworthy study was performed by Sydney Brenner and collaborators using "amber" mutants defective in the gene encoding the major head protein of bacteriophage T4. This study demonstrated the co-linearity of the gene with its encoded polypeptide, thus providing strong evidence for the "sequence hypothesis" that the amino acid sequence of a protein is specified by the nucleotide sequence of the gene determining the protein.