In molecular biology,
Human accelerated region 1 (highly accelerated region 1, HAR1) is a segment of the
human genomeThe human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
found on the long arm of chromosome 20. It is a Human accelerated region. It is located within a pair of overlapping long non-coding RNA
genesGênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
, HAR1A (HAR1F) and HAR1B (HAR1R).
HAR1A
HAR1A is expressed in
Cajal-Retzius cellThe term Cajal–Retzius cell is applied to reelin-producing neurons of the human embryonic marginal zone which display, as a salient feature, radial ascending processes that contact the pial surface, and a horizontal axon plexus located in the deep marginal zone...
s, where it colocalizes with the protein
reelinReelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...
.
HAR1A was identified in August 2006 when human accelerated regions (HARs) were first investigated. These 49 regions represent parts of the human genome which differ significantly from highly conserved regions of our closest ancestors evolutionarily. Because many of the HARs are associated with genes known to play a role in
neurodevelopmentNeural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms...
, HARs are believed to be responsible for the language, brain size, and complex thought which separate humans from other species. One particularly altered region, HAR1, was found in a stretch of genome with no known protein coding RNA sequences. Two RNA genes, HAR1F and HAR1R were identified partly within the region. The RNA structure of HAR1A has been shown to be stable, with a three–dimensional structure unlike those previously described.
HAR1A is active in the developing human brain between the 7th and 18th gestational weeks. It is found in the
dorsalIn anatomy, the dorsum is the upper side of animals that typically run, fly, or swim in a horizontal position, and the back side of animals that walk upright. In vertebrates the dorsum contains the backbone. The term dorsal refers to anatomical structures that are either situated toward or grow...
telencephalonThe cerebrum or telencephalon, together with the diencephalon, constitutes the forebrain. The cerebrum is the most anterior region of the vertebrate central nervous system. Telencephalon refers to the embryonic structure, from which the mature cerebrum develops...
in fetuses. In adult humans, it is found throughout the
cerebellumThe cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
and forebrain; it is also found in the testes. There is evidence that HAR1 is repressed by
RESTRE1-Silencing Transcription factor , also known as Neuron-Restrictive Silencer Factor , is a protein which in humans is encoded by the REST gene.- Function :...
in individuals with
Huntington's diseaseHuntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
, perhaps contributing to the
neurodegenerationNeurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many...
associated with the disease.
Further work on the
secondary structureBiomolecular structure is the structure of biomolecules, mainly proteins and the nucleic acids DNA and RNA. The structure of these molecules is frequently decomposed into primary structure, secondary structure, tertiary structure, and quaternary structure. The scaffold for this structure is...
of HAR1A has suggested that the human form adopts a different fold to that of other mammals exemplified by the chimpanzee sequence.
HAR1B
The HAR1B gene overlaps HAR1A, and is located on the opposite strand of the
chromosomeA chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
. Its expression in the human brain is lower than that of HAR1A.
Further reading
External links