Human accelerated regions (HARs), first described in August 2006, are a set of 49 segments of the

human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...

that are conserved throughout

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, ...

evolution but are strikingly different in

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

s. They are named according to their degree of difference between humans and

chimpanzee The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close relative th ...

s (HAR1 showing the largest degree of human-chimpanzee differences). Found by scanning through genomic databases of multiple species, some of these highly

mutated 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, mitos ...

areas may contribute to human-specific traits. Others may represent loss of functional mutations, possibly due to the action of biased

gene conversion Gene conversion is the process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion event. Gene conversion can be either allelic, meaning that one allele of the same gene replaces a ...

rather than

adaptive evolution In biology, adaptation has three related meanings. Firstly, it is the dynamic evolutionary process of natural selection that fits organisms to their environment, enhancing their evolutionary fitness. Secondly, it is a state reached by the po ...

Several of the HARs encompass genes known to produce proteins important in neurodevelopment. HAR1 is a 106-base pair stretch found on the long arm of

chromosome 20 Chromosome 20 is one of the 23 pairs of chromosomes in humans. Chromosome 20 spans around 66 million base pairs (the building material of DNA) and represents between 2 and 2.5 percent of the total DNA in cells. Chromosome 20 was fully sequenced i ...

overlapping with part of the

RNA gene A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non- ...

HAR1F In molecular biology, Human accelerated region 1 (highly accelerated region 1, HAR1) is a segment of the human genome found on the long arm of chromosome 20. It is a Human accelerated region. It is located within a pair of overlapping long non-cod ...

and HAR1R. HAR1F is active in the developing human brain. The HAR1 sequence is found (and conserved) in chickens and chimpanzees but is not present in fish or frogs that have been studied. There are 18 base pair mutations different between humans and chimpanzees, far more than expected by its history of conservation.supplement
/ref> HAR2 includes

HACNS1 Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 is an enzyme that in humans is encoded by the ''AGAP1'' gene. Function CENTG2 belongs to an ADP-ribosylation factor GTPase-activating (ARF-GAP) protein family involved in membra ...

gene enhancer In genetics, an enhancer is a short (50–1500 bp) region of DNA that can be bound by proteins ( activators) to increase the likelihood that transcription of a particular gene will occur. These proteins are usually referred to as transcriptio ...

"that may have contributed to the evolution of the uniquely opposable human

thumb The thumb is the first digit of the hand, next to the index finger. When a person is standing in the medical anatomical position (where the palm is facing to the front), the thumb is the outermost digit. The Medical Latin English noun for thumb ...

, and possibly also modifications in the

ankle The ankle, or the talocrural region, or the jumping bone (informal) is the area where the foot and the leg meet. The ankle includes three joints: the ankle joint proper or talocrural joint, the subtalar joint, and the inferior tibiofibular join ...

foot The foot ( : feet) is an anatomical structure found in many vertebrates. It is the terminal portion of a limb which bears weight and allows locomotion. In many animals with feet, the foot is a separate organ at the terminal part of the leg made ...

that allow humans to

walk Walking (also known as ambulation) is one of the main gaits of terrestrial locomotion among legged animals. Walking is typically slower than running and other gaits. Walking is defined by an 'inverted pendulum' gait in which the body vaults ov ...

on two legs". Evidence to date shows that of the 110,000 gene enhancer sequences identified in the human

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

, HACNS1 has undergone the most change during the

evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...

of humans following the split with the ancestors of

s. The substitutions in HAR2 may have resulted in loss of binding sites for a repressor, possibly due to biased gene conversion.

HAR-associated genes

* HAR01: HAR1F & HAR1R *HAR02: CENTG2 including

*HAR03:

MAD1L1 Mitotic spindle assembly checkpoint protein MAD1 is a protein that in humans is encoded by the ''MAD1L1'' gene. MAD1L1 is also known as Human Accelerated Region 3. It may have played a key role in the evolution of humans from apes. Function ...

*HAR04: *HAR05:

WNK1 WNK (lysine deficient protein kinase 1), also known as WNK1, is an enzyme that is encoded by the ''WNK1'' gene. WNK1 is serine-threonine protein kinase and part of the "with no lysine/K" kinase WNK family. The predominant role of WNK1 is the regu ...

*HAR06:

WWOX WW domain-containing oxidoreductase is an enzyme that in humans is encoded by the ''WWOX'' gene. Function WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular func ...

*HAR07: *HAR08: POU6F2 *HAR09:

PTPRT Receptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the ''PTPRT'' gene. PTPRT is also known as PTPrho, PTPρ and human accelerated region 9. The human accelerated regions are 49 regions of the human genome that ...

*HAR10:

FHIT Bis(5'-adenosyl)-triphosphatase also known as fragile histidine triad protein (FHIT) is an enzyme that in humans is encoded by the ''FHIT'' gene. Function FHIT is also known as human accelerated region 10. It may, therefore, have played a key ...

*HAR11: DMD *HAR12: EBF *HAR20:

PPARGC1A Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a protein that in humans is encoded by the ''PPARGC1A'' gene. PPARGC1A is also known as human accelerated region 20 ( HAR20). It may, therefore, have played a key ro ...

*HAR21:

NPAS3 NPAS3 or Neuronal PAS domain protein 3 is a brain-enriched transcription factor belonging to the bHLH-PAS superfamily of transcription factors, the members of which carry out diverse functions, including circadian oscillations, neurogenesis, to ...

- association with psychiatric disorders *HAR23: MGC27016 *HAR24: SCAP2 *HAR28: LPHN4 *HAR31: AUTS2 *HAR33: TBC1D22A *HAR38:

ITPR1 Inositol 1,4,5-trisphosphate receptor type 1 is a protein that in humans is encoded by the ''ITPR1'' gene. Interactions ITPR1 has been shown to interact with: * AHCYL1, * CA8, * EPB41L1 * FKBP1A, * MRVI1, * PRKG1, * RHOA Transform ...

*HAR40: ZBTB16 *HAR43: AGBL4 *HAR44:

*HAR45:

POLA Pola or POLA may refer to: People * House of Pola, an Italian noble family * Pola Alonso (1923–2004), Argentine actress * Pola Brändle (born 1980), German artist and photographer * Pola Gauguin (1883–1961), Danish painter * Pola Gojawiczyńsk ...

*HAR47: KLHL14

References

{{reflist Molecular genetics Human genetics Human evolution

HAR-associated genes

See also

References