A polyglutamine tract or polyQ tract is a portion of a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

consisting of a sequence of several

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...

units. A tract typically consists of about 10 to a few hundred such units. A multitude 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 b ...

s, in various eukaryotic species (including humans), contain a number of repetitions of the

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 biomolecu ...

triplet C A G or C A A. When the gene is

translated Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

into a protein, each of these triplets gives rise to a glutamine unit, resulting in a polyglutamine tract. Different

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chrom ...

s of such a gene often have different numbers of triplets since the highly repetitive sequence is prone to contraction and expansion. Several inheritable

neurodegenerative disorder A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

s, the

polyglutamine disease Trinucleotide repeat disorders, also known as microsatellite expansion diseases, are a set of over 50 genetic disorders caused by trinucleotide repeat expansion, a kind of mutation in which repeats of three nucleotides ( trinucleotide repeats) in ...

s, occur if a

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

causes a polyglutamine tract in a specific gene to become too long. Important examples of polyglutamine diseases are spinocerebellar ataxia and

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...

. Trinucleotide repeat expansion occurring in a parental

germline In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They ...

cell can lead to children that are more affected or display an earlier onset and greater severity of the condition. Trinucleotide repeat expansion is considered to be a consequence of

slipped strand mispairing Slipped strand mispairing (SSM), (also known as replication slippage), is a mutation process which occurs during DNA replication. It involves denaturation and displacement of the DNA strands, resulting in mispairing of the complementary bases. ...

either during

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritan ...

DNA repair 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 d ...

synthesis. It is believed that cells cannot properly dispose of proteins with overlong polyglutamine tracts, which over time leads to damage in

nerve cell A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. No ...

s. The longer the polyglutamine tract, the earlier in life these diseases tend to appear.Laura Bonetta
Polyglutamine Diseases: A Devastating Genetic Stutter
,

Howard Hughes Medical Institute The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization based in Chevy Chase, Maryland. It was founded in 1953 by Howard Hughes, an American business magnate, investor, record-setting pilot, engineer, fi ...

. Retrieved 30 December 2008.

History

Nucleotide sequences encoding a lengthy polyQ tract were first noted in the gene encoding the

Notch receptor __NOTOC__ __FORCETOC__ Notch proteins are a family of type-1 transmembrane proteins that form a core component of the Notch signaling pathway, which is highly conserved in metazoans. The Notch extracellular domain mediates interactions with DSL ...

. Variation of the length of this Notch polyQ tract, as caused by triplet repeat instability, was later found to cause

developmental Development of the human body is the process of growth to maturity. The process begins with fertilization, where an egg released from the ovary of a female is penetrated by a sperm cell from a male. The resulting zygote develops through mitosi ...

defects. The significance of similarly expanded tracts in humans became evident when polyQ tracts were found to underlie

and several spinocerebellar ataxias. In general, several neurodegenerative disorders were found to involve nucleotide repeat expansions in

coding sequences.

References

{{reflist Peptide sequences Mutation