Junctional diversity describes the DNA sequence variations introduced by the improper joining of

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

segments during the process of

V(D)J recombination V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell re ...

. This process of V(D)J recombination has vital roles for the

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

, as it is able to generate a huge repertoire of different

T-cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...

(TCR) and

immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

molecules required for

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

recognition by T-cells and B cells, respectively.

Process

Junctional diversity includes the process of somatic recombination or

, during which the different variable gene segments (those segments involved in antigen recognition) of TCRs and immunoglobulins are rearranged and unused segments removed. This introduces

double-strand breaks DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dama ...

between the required segments. These ends form hairpin loops and must be joined together to form a single strand (summarised in diagram, right). This joining is a very inaccurate process that results in the variable addition or subtraction of

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...

s and, thus, generates junctional diversity. Generation of junctional diversity starts as the proteins,

recombination activating gene The recombination-activating genes (RAGs) encode parts of a protein complex that plays important roles in the rearrangement and recombination of the genes encoding immunoglobulin and T cell receptor molecules. There are two recombination-activa ...

-1 and -2 (RAG1 and RAG2), along with DNA repair proteins, such as

Artemis In ancient Greek mythology and religion, Artemis (; grc-gre, Ἄρτεμις) is the goddess of the hunt, the wilderness, wild animals, nature, vegetation, childbirth, care of children, and chastity. She was heavily identified wit ...

, are responsible for single-stranded cleavage of the hairpin loops and addition of a series of

palindromic A palindrome is a word, number, phrase, or other sequence of symbols that reads the same backwards as forwards, such as the words ''madam'' or ''racecar'', the date and time ''11/11/11 11:11,'' and the sentence: "A man, a plan, a canal – Pana ...

, 'P' nucleotides. Subsequent to this, the enzyme,

terminal deoxynucleotidyl transferase Terminal deoxynucleotidyl transferase (TdT), also known as DNA nucleotidylexotransferase (DNTT) or terminal transferase, is a specialized DNA polymerase expressed in immature, pre-B, pre-T lymphoid cells, and acute lymphoblastic leukemia/lymphom ...

(TdT), adds further random 'N' nucleotides. The newly synthesised strands anneal to one another, but mismatches are common. Exonucleases remove these unpaired nucleotides and the gaps are filled by

DNA synthesis DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. DNA is a macromolecule made up of nucleotide units, which are linked by covalent bonds and hydrogen bonds, in a repeating structure. DNA synthesis occurs ...

and

repair The technical meaning of maintenance involves functional checks, servicing, repairing or replacing of necessary devices, equipment, machinery, building infrastructure, and supporting utilities in industrial, business, and residential installa ...

machinery. Exonucleases may also cause shortening of this junction, however this process is still poorly understood. Junctional diversity is liable to cause

frame-shift mutation A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels (gene insertion, insertions or genetic deletion, deletions) of a number of nucleotides in a DNA sequence that is not divisible by ...

s and thus production of non-functional proteins. Therefore, there is considerable waste involved in this process.

References

{{DEFAULTSORT:Junctional Diversity Immune system Lymphocytes