HAR1
Human accelerated regions (HARs), first described in August 2006,[1][2] are a set of 49 segments of the human genome which are conserved throughout vertebrate evolution but are strikingly different in humans. They are named HAR1 through HAR49 according to their degree of difference between humans and chimpanzees
(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.[1]
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 chimpanzees.[3]
The scientists found 49 candidate segments. These segments have evolved a lot in our lineage. The most drastically altered of all is a segment the scientists dubbed HAR1 (for human accelerated region). It is 118 base pairs long. Chimpanzees and chickens, separated by over 300 million years, carry versions of HAR1 that are identical except for two base pairs. In humans, on the other hand, 18 base pairs have changed since we split from chimps.
What's HAR1 for? This is the sort of question that seems like it should be easy to answer unless you're the scientist doing the answering. The scientists found that human cells make RNA molecules out of the HAR1 segment. Specifically, they found that brain cells do. Specifically, brain cells in the cortex, the hippocampus, and certain other regions. We do love our brains, and so it is reasonable to consider that HAR1 took on some new role in the brains of human ancestors. The sequence of HAR1 suggests that an RNA molecule produced from it would be stable enough to carry out some important job, such as regulating the activity of protein-coding genes. HAR1 probably plays several roles. It is not just active in the adult brain, but in development-guiding cells in the fetus.
In a commentary that also appears in Nature, two Oxford scientists point out that HAR1 is also active in the ovary and testis of adult humans. And it is true that genes associated with sex are fast-evolving. So they don't want to rule out the possibility that selection has acted on HAR1 in connection with reproduction, rather than with thought. It's a fair point, but I was struck by the fact that the expression of HAR1 is far smaller in the sex cells than in the brain.
Still, it's a strange point that may be worth raising at your next party: we have genes that are only active in our brains and sex cells.Elsewhere I read this gene is most active in humans from 7-19 weeks of gestation.
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.[1]
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 chimpanzees.[3]
The scientists found 49 candidate segments. These segments have evolved a lot in our lineage. The most drastically altered of all is a segment the scientists dubbed HAR1 (for human accelerated region). It is 118 base pairs long. Chimpanzees and chickens, separated by over 300 million years, carry versions of HAR1 that are identical except for two base pairs. In humans, on the other hand, 18 base pairs have changed since we split from chimps.
What's HAR1 for? This is the sort of question that seems like it should be easy to answer unless you're the scientist doing the answering. The scientists found that human cells make RNA molecules out of the HAR1 segment. Specifically, they found that brain cells do. Specifically, brain cells in the cortex, the hippocampus, and certain other regions. We do love our brains, and so it is reasonable to consider that HAR1 took on some new role in the brains of human ancestors. The sequence of HAR1 suggests that an RNA molecule produced from it would be stable enough to carry out some important job, such as regulating the activity of protein-coding genes. HAR1 probably plays several roles. It is not just active in the adult brain, but in development-guiding cells in the fetus.
In a commentary that also appears in Nature, two Oxford scientists point out that HAR1 is also active in the ovary and testis of adult humans. And it is true that genes associated with sex are fast-evolving. So they don't want to rule out the possibility that selection has acted on HAR1 in connection with reproduction, rather than with thought. It's a fair point, but I was struck by the fact that the expression of HAR1 is far smaller in the sex cells than in the brain.
Still, it's a strange point that may be worth raising at your next party: we have genes that are only active in our brains and sex cells.Elsewhere I read this gene is most active in humans from 7-19 weeks of gestation.
BRAIN EVOLUTION & UNIQUENESS OF THE HUMAN GENOME
http://www.nslc.wustl.edu/courses/bio3411/woolsey/2010/Lecture15/Amado%20&%20Walsh%202006.pdf
http://www.nslc.wustl.edu/courses/bio3411/woolsey/2010/Lecture15/Amado%20&%20Walsh%202006.pdf
HAR 1 - Special Gene - Only Human - From the Stars, Evolution, Aliens or God?
They have recently drawn a name for the only gene that humans have that is not also in other mammals. For those misanthropes among us, you could say: "Aha, the killer, war making gene", but for the rest of us less enlightened it is the peace making, come let us reason together, let's draw pictures in the sand and make love, just because we can gene. Whatever makes us human. Now that's a complicated one. I can't wait until they can study this gene more. A world of contradictory complexities I bet.
I Feel More Like I Do Now Than I Did When I Came In
There is an old backward drunken phrase from the denizen of those kinds of thoughts - Texas. It makes perfect sense to a drunk. And it seems quite appropriate at this point in the Human DNA discussion. After years studying the human genome (only 5% is really accessible and comprehensive to us right now) There is this "HAR 1" that is only human. Scientists can stare at it and philosophers and ponderers and religionists can go cross-eyed speculating about it. The point is: IT WAS THERE A VERY LONG TIME AGO. AND IT IS WITH US NOW. PERHAPS IT IS THE THING THAT KEEPS ON MAKING US PROGRESS (technologically, industrially, scientifically). So, "we feel more like we do now than we did when we came in". This HAR 1 declares by its very existence that there is a genetic distinction that makes us human. It is not in any other creature, no other mammal. Of course, this only begins the discussion, and that's where I intend to start.
Quick, Quick, With The Arguments
"When we came in". Now there is where the contention begins. There is the creationist take: God said, "I'm gonna make me a man!" And the HAR 1 started. Evolutionists say: "Throw some millions of years around and it could evolve". Alien Incursionists/Interventionists claim. "It came from outer space". Thus, HAR 1 is probably one of the key remnants of the alien DNA that we got when they said: "We are going to make us a homo sapien from this here Ape."
The point of this article is not to try to reconcile these arguments, or to persuade one or two to go over to the other point of view. That would be like trying to get a Buddhist, a Western Hedonist Secularist and an Islamist to agree. But rather this HAR 1 is the part of our code that ALLOWS us to argue.
HAR 1 - "Hardee harhar". "What you say?" "We are so much more civilized than those guys over there."
This guy is the thing that allows us to laugh. Do dogs laugh? (Forget hyenas for the moment). Amazement, scorn and awe. These are the human things that make this life worth living. Whenever this HAR 1 came in, or got configured or evolved, it made us distinctly "children of God", "Alien subdudes" or highly evolved "tricky dicky Apes". Again, however it happened, it made us us. It made us able to argue, pose subjective points of view, invent religion, establish science, think of the idea of research, write books about behavior, create traditions of law, love, civilization and war. It allows us to become skeptical, superior, arrogant, noisome irritating obnoxious types or "loverly" little girls.
The fact that we came up with the ability to stare down into the Human Genome came from HAR 1 is what is amazing. The fact that no one has told us about "beginnings" means that it is through HAR 1 that we can even discuss beginnings. Taken to its height. You can see how HAR 1 has led us to kill with justification in the act of war. The nuances of law and they are nuanced, all must tip their hat to the human ability to reason, make distinctions decide why this exceptional point should rule, and why this less than elegant point should dominate. The ability to decide between the irreconcilable and come to a new epiphany from a mass of confusing data.
Self Interest, Social Interest and Human Interest
HAR 1, the only element that is distinctive from animals, is an elegant gift because it allows us to be selfish, to be socially concerned and to be aware of all of us --- and we can do them all at the same time. And just like fighting for Democracy means you may be fighting for the freedom of a man who wants to spit on your grave, HAR 1 means that we can conjure up dreams from animalistic imagination to create a reason for pushing citizens into special situations that they were not born to -- all in the name of some "good". And so, if you want to give yourself a headache, think of all the things that mankind does that are first engendered because they come from some good (and how bad they end up being for most). This little DNA construction is probably likened to a famous Greek Symbol.
Pandora's Box
People have been writing about the symbolism of Pandora's Box for generations. I would like to pose another. The study of the Human Genome as the decades go on will be the source of so much confusion, clarity, argument and insight, that we can not possibly see it now. But, alas, as the decades have passed, I predict that the Study of the Human Genome will be the Ultimate Pandora's Box.
What is your HAR 1 Rating?
Perhaps at some time in the future a test will be devised which can demonstrate how much or how highly or how sophisticatedly you use your HAR 1.
"I have a 95 rating, what is yours?"
"They say he was a great guy, but his HAR 1 rating was ridiculously low. His epitaph will be that he was a fantastic actor."
"They say that her HAR 1 rating is so high that it is difficult for her to even socialize with the rest of us low lifes"
"Everybody in that family had super low HAR 1, then out comes this great humanistic artist".
Infallible?
Just a few years ago, you would have a very hard time even explaining "cap and trade" and why those taxes should even exist. Just a few decades ago, the idea that there should be laws with a "social conscience" was very far from most people's consciousness. This HAR 1 makes us human, but you know what I know? It does not make us infallible. Because we are fallible, and the most fallible are the ones who think they are not fallible. A whole line of research could be developed over how our sense of righteousness, importance, intelligence and profundity all lead us down very dark roads. As you think about being human, and what ultimately the study of HAR 1 might reap, is that it leads us inevitably with the challenge that we have been fighting with over the millenia: "How do we reconcile what we feel we know?"
And this doubt should inform us. It might be advisable to think about where humility and modesty and self-reflection come from. Perhaps that will be the ultimate legacy of HAR 1. When we can delve more deeply into our biological makeup and thus the psychological profile of homo sapien, maybe we will discover oddities, profundities and sensibilities that make us fall back in dismay, or reach for the stars in triumph. No one knows, but you have to admit it is an incredible mystery.
Article Source: http://EzineArticles.com/4748079
They have recently drawn a name for the only gene that humans have that is not also in other mammals. For those misanthropes among us, you could say: "Aha, the killer, war making gene", but for the rest of us less enlightened it is the peace making, come let us reason together, let's draw pictures in the sand and make love, just because we can gene. Whatever makes us human. Now that's a complicated one. I can't wait until they can study this gene more. A world of contradictory complexities I bet.
I Feel More Like I Do Now Than I Did When I Came In
There is an old backward drunken phrase from the denizen of those kinds of thoughts - Texas. It makes perfect sense to a drunk. And it seems quite appropriate at this point in the Human DNA discussion. After years studying the human genome (only 5% is really accessible and comprehensive to us right now) There is this "HAR 1" that is only human. Scientists can stare at it and philosophers and ponderers and religionists can go cross-eyed speculating about it. The point is: IT WAS THERE A VERY LONG TIME AGO. AND IT IS WITH US NOW. PERHAPS IT IS THE THING THAT KEEPS ON MAKING US PROGRESS (technologically, industrially, scientifically). So, "we feel more like we do now than we did when we came in". This HAR 1 declares by its very existence that there is a genetic distinction that makes us human. It is not in any other creature, no other mammal. Of course, this only begins the discussion, and that's where I intend to start.
Quick, Quick, With The Arguments
"When we came in". Now there is where the contention begins. There is the creationist take: God said, "I'm gonna make me a man!" And the HAR 1 started. Evolutionists say: "Throw some millions of years around and it could evolve". Alien Incursionists/Interventionists claim. "It came from outer space". Thus, HAR 1 is probably one of the key remnants of the alien DNA that we got when they said: "We are going to make us a homo sapien from this here Ape."
The point of this article is not to try to reconcile these arguments, or to persuade one or two to go over to the other point of view. That would be like trying to get a Buddhist, a Western Hedonist Secularist and an Islamist to agree. But rather this HAR 1 is the part of our code that ALLOWS us to argue.
HAR 1 - "Hardee harhar". "What you say?" "We are so much more civilized than those guys over there."
This guy is the thing that allows us to laugh. Do dogs laugh? (Forget hyenas for the moment). Amazement, scorn and awe. These are the human things that make this life worth living. Whenever this HAR 1 came in, or got configured or evolved, it made us distinctly "children of God", "Alien subdudes" or highly evolved "tricky dicky Apes". Again, however it happened, it made us us. It made us able to argue, pose subjective points of view, invent religion, establish science, think of the idea of research, write books about behavior, create traditions of law, love, civilization and war. It allows us to become skeptical, superior, arrogant, noisome irritating obnoxious types or "loverly" little girls.
The fact that we came up with the ability to stare down into the Human Genome came from HAR 1 is what is amazing. The fact that no one has told us about "beginnings" means that it is through HAR 1 that we can even discuss beginnings. Taken to its height. You can see how HAR 1 has led us to kill with justification in the act of war. The nuances of law and they are nuanced, all must tip their hat to the human ability to reason, make distinctions decide why this exceptional point should rule, and why this less than elegant point should dominate. The ability to decide between the irreconcilable and come to a new epiphany from a mass of confusing data.
Self Interest, Social Interest and Human Interest
HAR 1, the only element that is distinctive from animals, is an elegant gift because it allows us to be selfish, to be socially concerned and to be aware of all of us --- and we can do them all at the same time. And just like fighting for Democracy means you may be fighting for the freedom of a man who wants to spit on your grave, HAR 1 means that we can conjure up dreams from animalistic imagination to create a reason for pushing citizens into special situations that they were not born to -- all in the name of some "good". And so, if you want to give yourself a headache, think of all the things that mankind does that are first engendered because they come from some good (and how bad they end up being for most). This little DNA construction is probably likened to a famous Greek Symbol.
Pandora's Box
People have been writing about the symbolism of Pandora's Box for generations. I would like to pose another. The study of the Human Genome as the decades go on will be the source of so much confusion, clarity, argument and insight, that we can not possibly see it now. But, alas, as the decades have passed, I predict that the Study of the Human Genome will be the Ultimate Pandora's Box.
What is your HAR 1 Rating?
Perhaps at some time in the future a test will be devised which can demonstrate how much or how highly or how sophisticatedly you use your HAR 1.
"I have a 95 rating, what is yours?"
"They say he was a great guy, but his HAR 1 rating was ridiculously low. His epitaph will be that he was a fantastic actor."
"They say that her HAR 1 rating is so high that it is difficult for her to even socialize with the rest of us low lifes"
"Everybody in that family had super low HAR 1, then out comes this great humanistic artist".
Infallible?
Just a few years ago, you would have a very hard time even explaining "cap and trade" and why those taxes should even exist. Just a few decades ago, the idea that there should be laws with a "social conscience" was very far from most people's consciousness. This HAR 1 makes us human, but you know what I know? It does not make us infallible. Because we are fallible, and the most fallible are the ones who think they are not fallible. A whole line of research could be developed over how our sense of righteousness, importance, intelligence and profundity all lead us down very dark roads. As you think about being human, and what ultimately the study of HAR 1 might reap, is that it leads us inevitably with the challenge that we have been fighting with over the millenia: "How do we reconcile what we feel we know?"
And this doubt should inform us. It might be advisable to think about where humility and modesty and self-reflection come from. Perhaps that will be the ultimate legacy of HAR 1. When we can delve more deeply into our biological makeup and thus the psychological profile of homo sapien, maybe we will discover oddities, profundities and sensibilities that make us fall back in dismay, or reach for the stars in triumph. No one knows, but you have to admit it is an incredible mystery.
Article Source: http://EzineArticles.com/4748079
Scientific American
What Makes Us Human?
Comparisons of the genomes of humans and chimpanzees are revealing those
rare stretches of DNA that are ours alone
By Katherine S. Pollard | April 20, 2009
http://www.scientificamerican.com/article.cfm?id=what-makes-us-human
What Makes Us Human?
Comparisons of the genomes of humans and chimpanzees are revealing those
rare stretches of DNA that are ours alone
By Katherine S. Pollard | April 20, 2009
http://www.scientificamerican.com/article.cfm?id=what-makes-us-human
The DNA sequences of humans and chimpanzees are 98 percent identical.
Yet that 2 percent difference represents at least 15 million changes in
our genome since the time of our common ancestor roughly six million
years ago. Now a new computational technique has identified 49 regions
that have changed particularly quickly between humans and chimps, and
may have revealed at least one gene critical to the development of our
larger brains.
Katherine Pollard of the University of California, Davis, first used computers to search for segments of DNA that showed the most changes between human and chimp genomes. The computers identified 49 such areas in the human genome, dubbed human accelerated regions (HAR). The most radical revolutionary, tagged as HAR1, transformed 18 of its 118 nucleotides in the course of the last few million years; only two had changed in the prior 310 million years that separate chickens from apes. "It's really an extreme case," Pollard notes.
Closer observation of the region by Sofie Salama of the University of California, Santa Cruz, revealed that it overlaps with two neighboring genes: HAR1F and HAR1R. These genes do not code for proteins that then carry out a particular function in the body, rather they produce a messenger RNA (mRNA) molecule that guides the production of proteins by other genes.
Further experiments by an international team of collaborators revealed that HAR1F is strongly expressed in the developing neocortex of human embryos, starting in the seventh week. The mRNA is produced by Cajal-Retzius neurons, which previous research has shown to direct the creation of the layers of neurons in the human cortex. These cells also produce the protein reelin, which helps create the architecture of the human brain. The corresponding gene in other primates plays a similar role, according to experiments with crab-eating macaques.
Although this research does not definitively link this region to brain differences between humans and our closest relatives, it is intriguing. "We don't know what it does, and we don't know if it interacts with reelin, but the evidence is very suggestive that this gene is important in the development of the cerebral cortex, and that's exciting because the human cortex is three times as large as it was in our predecessors," notes team leader David Haussler of the University of California, Santa Cruz. "Something caused our brains to evolve to be much larger and have more function than the brains of other mammals."
Katherine Pollard of the University of California, Davis, first used computers to search for segments of DNA that showed the most changes between human and chimp genomes. The computers identified 49 such areas in the human genome, dubbed human accelerated regions (HAR). The most radical revolutionary, tagged as HAR1, transformed 18 of its 118 nucleotides in the course of the last few million years; only two had changed in the prior 310 million years that separate chickens from apes. "It's really an extreme case," Pollard notes.
Closer observation of the region by Sofie Salama of the University of California, Santa Cruz, revealed that it overlaps with two neighboring genes: HAR1F and HAR1R. These genes do not code for proteins that then carry out a particular function in the body, rather they produce a messenger RNA (mRNA) molecule that guides the production of proteins by other genes.
Further experiments by an international team of collaborators revealed that HAR1F is strongly expressed in the developing neocortex of human embryos, starting in the seventh week. The mRNA is produced by Cajal-Retzius neurons, which previous research has shown to direct the creation of the layers of neurons in the human cortex. These cells also produce the protein reelin, which helps create the architecture of the human brain. The corresponding gene in other primates plays a similar role, according to experiments with crab-eating macaques.
Although this research does not definitively link this region to brain differences between humans and our closest relatives, it is intriguing. "We don't know what it does, and we don't know if it interacts with reelin, but the evidence is very suggestive that this gene is important in the development of the cerebral cortex, and that's exciting because the human cortex is three times as large as it was in our predecessors," notes team leader David Haussler of the University of California, Santa Cruz. "Something caused our brains to evolve to be much larger and have more function than the brains of other mammals."
En Espanol
HAR1F
HAR1F is a RNA gene which is part of a human accelerated region of the human genome. HAR1F is found on the long arm of chromosome 20 and the RNA product is expressed in Cajal-Retzius cells, where it colocalizes with the protein reelin. [1][2][3]
HAR1F 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 neurodevelopment, 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 HAR1F has been shown to be stable, with a three–dimensional structure unlike those previously described.
HAR1F is active in the developing human brain between the 7th and 18th gestational weeks. It is found in the dorsaltelencephalon in fetuses. In adult humans, it is found throughout the cerebellum and forebrain; it is also found in the testes.[1] There is evidence that HAR1 is repressed by REST in individuals with Huntington's disease, perhaps contributing to the neurodegeneration associated with the disease.[4]
Further work on the secondary structure of HAR1F has suggested that the human form adopts a different fold to that of other mammals exemplified by the chimpanzee sequence.[5]
HAR1F 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 neurodevelopment, 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 HAR1F has been shown to be stable, with a three–dimensional structure unlike those previously described.
HAR1F is active in the developing human brain between the 7th and 18th gestational weeks. It is found in the dorsaltelencephalon in fetuses. In adult humans, it is found throughout the cerebellum and forebrain; it is also found in the testes.[1] There is evidence that HAR1 is repressed by REST in individuals with Huntington's disease, perhaps contributing to the neurodegeneration associated with the disease.[4]
Further work on the secondary structure of HAR1F has suggested that the human form adopts a different fold to that of other mammals exemplified by the chimpanzee sequence.[5]
maybe, maybe not