Human accelerated regions
Encyclopedia
Human accelerated regions (HARs), first described in August 2006, are a set of 49 segments of the human genome
which are conserved throughout vertebrate
evolution but are strikingly different in human
s. They are named HAR1 through HAR49 according to their degree of difference between humans and chimpanzee
s (HAR1 showing the largest degree of human-chimpanzee differences of the 49). Found by scanning through genomic databases of multiple species, some of these highly mutated
areas are thought to have contributed to the development of human neuroanatomy, language, and complex thought.
Several of the HARs encompass genes known to produce proteins important in neurodevelopment. HAR1 is an 118 base pair stretch found on the long arm of chromosome 20 overlapping with part of the RNA genes HAR1F
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.
HAR2 includes HACNS1 a gene enhancer
"that may have contributed to the evolution of the uniquely opposable human thumb
, and possibly also modifications in the ankle
or foot
that allow humans to walk
on two legs". Evidence to date shows that of the 110,000 gene enhancer sequences identified in the human genome
, HACNS1 has undergone the most change during the evolution
of humans following the split with the ancestors of chimpanzee
s.
Human genome
The 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...
which are conserved throughout vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
evolution but are strikingly different in human
Human
Humans are the only living species in the Homo genus...
s. They are named HAR1 through HAR49 according to their degree of difference between humans and chimpanzee
Chimpanzee
Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...
s (HAR1 showing the largest degree of human-chimpanzee differences of the 49). Found by scanning through genomic databases of multiple species, some of these highly mutated
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
areas are thought to have contributed to the development of human neuroanatomy, language, and complex thought.
Several of the HARs encompass genes known to produce proteins important in neurodevelopment. HAR1 is an 118 base pair stretch found on the long arm of chromosome 20 overlapping with part of the RNA genes HAR1F
HAR1F
In molecular biology, Human accelerated region 1 is a segment of the human genome found on the long arm of chromosome 20. It is a Human accelerated region...
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.
HAR2 includes HACNS1 a gene enhancer
Enhancer (genetics)
In genetics, an enhancer is a short region of DNA that can be bound with proteins to enhance transcription levels of genes in a gene cluster...
"that may have contributed to the evolution of the uniquely opposable human thumb
Thumb
The thumb is the first digit of the hand. When a person is standing in the medical anatomical position , the thumb is the lateral-most digit...
, and possibly also modifications in the ankle
Ankle
The ankle joint is formed where the foot and the leg meet. The ankle, or talocrural joint, is a synovial hinge joint that connects the distal ends of the tibia and fibula in the lower limb with the proximal end of the talus bone in the foot...
or foot
Foot
The foot 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 up of one or more segments or bones, generally including claws...
that allow humans to walk
WALK
WALK may refer to:*WALK , a radio station licensed to East Patchogue, New York, United States*WALK-FM, a radio station licensed to Patchogue, New York, United States...
on two legs". Evidence to date shows that of the 110,000 gene enhancer sequences identified in the human genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
, HACNS1 has undergone the most change during the evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
of humans following the split with the ancestors of chimpanzee
Chimpanzee
Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...
s.
HAR-associated genes
- HAR01: HAR1F & HAR1R
- HAR02: CENTG2CENTG2Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 is an enzyme that in humans is encoded by the AGAP1 gene.-HACNS1:HACNS1 is located in an intron of the gene CENTG2...
including HACNS1 - HAR03: MAD1L1
- HAR04:
- HAR05: WNK1WNK1WNK lysine deficient protein kinase 1, also known as WNK1, is an enzyme which in humans is encoded by the WNK1 gene. The human gene is located on short arm of chromosome 12 .WNK1 is also known as Human Accelerated Region 5...
- HAR06: WWOXWWOXWW 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 functions such as protein degradation, transcription, and RNA...
- HAR07:
- HAR08: POU6F2
- HAR09: PTPRTPTPRTReceptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the PTPRT gene.PTPRT is also known as human accelerated region 9. It may, therefore, have played a key role in differentiating humans from apes.-Further reading:...
- HAR10: FHITFHITBis-triphosphatase also known as fragile histidine triad protein is an enzyme that in humans is encoded by the FHIT gene.- Function :FHIT is also known as human accelerated region 10...
- HAR11: DMDDystrophinDystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex...
- HAR12: EBF
- HAR20: PPARGC1APPARGC1APeroxisome proliferator-activated receptor gamma coactivator 1-alpha is a protein that in humans is encoded by the PPARGC1A gene....
- HAR21: NPAS3NPAS3NPAS3 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, toxin metabolism, hypoxia, and tracheal development...
- association with psychiatric disorders - HAR23: MGC27016
- HAR24: SCAP2
- HAR28: LPHN4
- HAR31: AUTS2
- HAR33: TBC1D22A
- HAR38: ITPR1ITPR1Inositol 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 CA8, PRKG1, FKBP1A, MRVI1, RHOA, AHCYL1, EPB41L1 and TRPC4.-External Links:*...
- HAR40: ZBTB16
- HAR43: AGBL4
- HAR44: FHITFHITBis-triphosphatase also known as fragile histidine triad protein is an enzyme that in humans is encoded by the FHIT gene.- Function :FHIT is also known as human accelerated region 10...
- HAR45: POLADNA polymerase IDNA Polymerase I is an enzyme that participates in the process of DNA replication in prokaryotes. It is composed of 928 amino acids, and is an example of a processive enzyme - it can sequentially catalyze multiple polymerisations. Discovered by Arthur Kornberg in 1956, it was the first known...
- HAR47: KLHL14
Further reading
- What Makes Us Human?, Scientific AmericanScientific AmericanScientific American is a popular science magazine. It is notable for its long history of presenting science monthly to an educated but not necessarily scientific public, through its careful attention to the clarity of its text as well as the quality of its specially commissioned color graphics...
, May 2009 - Scientists Identify Gene Difference Between Humans and Chimps, Scientific AmericanScientific AmericanScientific American is a popular science magazine. It is notable for its long history of presenting science monthly to an educated but not necessarily scientific public, through its careful attention to the clarity of its text as well as the quality of its specially commissioned color graphics...
, 17 August 2006 - Researchers Identify Human DNA on the Fast Track, Howard Hughes Medical InstituteHoward Hughes Medical InstituteHoward Hughes Medical Institute is a United States non-profit medical research organization based in Chevy Chase, Maryland. It was founded by the American businessman Howard Hughes in 1953. It is one of the largest private funding organizations for biological and medical research in the United...
website, 16 August 2006.
External links
- Katherine Pollard's research group website
- A supplement to Pollard et al.'s article containing the list of HAR-associated genes