Tiny evolutionary mutation led to 'language gene': study
by Marlowe Hood, Yahoo News – Wed Nov 11, 12:19 pm ET
PARIS (AFP) – Two minute changes in a gene that is otherwise identical in humans and chimps could explain why we have full-fledged power of speech while other primates can only grunt or screech, scientists said on Wednesday.
The findings may also point to new drug targets for hard-to-treat diseases that disrupt speech, such as schizophrenia and autism, they said.
A decade ago, researchers discovered that members of an extended family beset with a rare inherited speech disorder all shared the same defect in a gene called FOXP2.
Investigators then found that a small number of patients with another speech-related disease, developmental dysphasia, also had mutations in the gene.
Separately, biologists studying FOXP2 in our closest evolutionary cousin, the chimpanzee, noticed that only two among the hundreds of amino acids in the protein coded by the gene differed across the two species.
The question emerged: Could this minor genetic variation be the key that enables human speech?
Some experts suggested the telltale pair of amino acids -- the building blocks of proteins -- were evidence of a "fast track" evolution toward language.
Others, though, argued that the molecules played no part in our ability to yammer and yak.
To find out who might be right, Daniel Geshwind, a professor at the University of California in Los Angeles, designed the first-ever experiments comparing the "ancestral" FOXP2 in chimps with the evolved variant in humans.
Apenas duas mutações na sequência de DNA do FOXP2 podem estar por trás da linguagem humana, mostra estudo
Experimentoamericano mostrou pela 1a vez como a versão humana desse gene altera a maneira como os neurônios funcionam
REINALDO JOSÉ LOPES
DA REPORTAGEM LOCAL
Modificações sutis num úni- co gene podem estar por trás da grande reorganização do cére- bro que deu aos ancestrais das pessoas de hoje a capacidade de falar. A conclusão vem de expe- rimentos feitos nos EUA, indi- cando que o trecho de DNA co- nhecido como FOXP2 real- mente mereceu ganhar o apeli- do de “gene da linguagem”.
Não é que, sozinho, o FOXP2 tenha “ensinado” hominídeos antes mudos a tagarelar, mas a versão tipicamente humana dele ajudou a alterar toda uma rede de genes importantes para o funcionamento dos neurô- nios, diz Daniel Geschwind, pesquisador da Universidade da Califórnia em Los Angeles que coordenou o estudo. “Podemos pensar no FOXP2 como uma janela para a lingua- gem, e para as vias moleculares que estão por trás dela. É clara- mente uma janela importante, mas não a única”, afirmou Geschwind à Folha.
WASHINGTON — Chimps, our nearest relative, don't talk. We do. Now scientists have pinpointed a mutation in a gene that might help explain the difference.
The mutation seems to have helped humans develop speech and language. It's probably not the only gene involved, but researchers found the gene looks and acts differently in chimps and humans, according to a study published online Wednesday by the journal Nature.
Lab tests showed that the human version regulated more than 100 other genes differently from the chimp version. This particular gene — called FOXP2 — mutated around the time humans developed the ability to talk.
"It's really playing a major role in chimp-human differences," said the study's author, Daniel Geschwind, a professor of neurology, psychiatry and human genetics at the University of California, Los Angeles. "You mutate this gene in humans and you get a speech and language disorder."
Of the 20,000 genes in the human genome, few are more fascinating than FOXP2, a gene that underlies the faculty of human speech.
All animals have an FOXP2 gene, but the human version’s product differs at just 2 of its 740 units from that of chimpanzees, suggesting that this tiny evolutionary fix may hold the key to why people can speak and chimps cannot.
FOXP2 came to light in a large London family, half of whose members have severe problems in articulating and understanding speech. All turned out to have a mutation that disrupted this vital gene.
This year, one inquiry bore fruit, although of a somewhat ambiguous nature, when biologists in Leipzig, Germany, genetically engineered a mouse with the human version of FOXP2 substituted for its own. The upgraded mice squeaked somewhat differently from plain mice and were born with subtle alterations in brain structure. But mice and people are rather distant cousins — their last common ancestor lived some 70 million years ago — and the human version of FOXP2 evidently was not able to exert a transformative effect on the mouse.
A scientific team led by Dr. Daniel H. Geschwind of the University of California, Los Angeles, has now completed a parallel experiment, which is to put the chimp version of FOXP2 into human neurons and see what happens. These were neurons living in laboratory glassware, not a human brain, so they gave a snapshot of FOXP2 only at the cellular level. But they confirmed suspicions that FOXP2 was a maestro of the genome.
UCLA scientists, in partnership with 30 research institutions across the country, have identified a new gene variant that is highly common in autistic children. And when researchers scrutinized the activity of the gene, known as CDH10, in the fetal brain, they discovered that it is most active in key regions that support language, speech and interpreting social behavior. Published April 28 in the advance online edition of the journal Nature, the two findings suggest that CDH10 plays a critical role in shaping the developing brain and may contribute to a prenatal risk of autism.
A variant is a gene that has undergone subtle changes from the normal DNA yet is shared by a significant portion of the population.
"While this gene variant is common in the general population, we discovered that it occurs about 20 percent more often in children with autism," said study author Dr. Daniel Geschwind, director of the UCLA Center for Autism Treatment and Research. "A major change like this in the genetic code is too common to be a simple mutation — it is a risk factor in the origin of the disease."
Two tiny changes in the sequence of one gene could have helped install the mechanisms of speech and language in humans.
In 2001, a gene called FOXP2 was found to underlie a rare inherited speech and language disorder1. It encodes a transcription factor called FOXP2, a protein 'dimmer-switch' that binds to DNA and helps to determine to what extent other genes are expressed as proteins.
Experiments have now revealed that the human version of FOXP2, which has two different amino acids compared with the version carried by chimps, has differing effects on genes in the brains of the two species. These differences could affect how the brain develops, and so explain why only humans are capable of language.
To find out whether these changes in FOXP2 had a biological function, a team led by Daniel Geschwind of the University of California, Los Angeles, inserted the two versions into human brain cells and looked at expression of the genes that the protein regulates. They found that the human version increased the expression of 61 genes and decreased the expression of 51 genes compared with the chimp version of the protein. To double-check that the same was happening in real brains, they looked at the expression of these genes in human and chimp brain tissue and found similar expression levels as in the cells. Their study is published in Nature2.
Why can't chimps speak? Study links evolution of single gene to human capacity for language
By Elaine Schmidt, UCLA Newsroom, November 11, 2009
If humans are genetically related to chimps, why did our brains develop the innate ability for language and speech while theirs did not?
Scientists suspect that part of the answer to the mystery lies in a gene called FOXP2. When mutated, FOXP2 can disrupt speech and language in humans. Now, a UCLA–Emory University study reveals major differences between how the human and chimp versions of FOXP2 work, perhaps explaining why language is unique to humans.
Published Nov. 11 in the online edition of the journal Nature, the findings provide insight into the evolution of the human brain and may point to possible drug targets for human disorders characterized by speech disruption, such as autism and schizophrenia.
"Earlier research suggests that the amino-acid composition of human FOXP2 changed rapidly around the same time that language emerged in modern humans," said Dr. Daniel Geschwind, Gordon and Virginia MacDonald Distinguished Chair in Human Genetics at the David Geffen School of Medicine at UCLA. "Ours is the first study to examine the effect of these amino-acid substitutions in FOXP2 in human cells.
By Jon Cohen ScienceNOW Daily News 11 November 2009
For the first time, scientists have compared a vast network of human genes responsible for speech and language with an analogous network in chimpanzees. The findings help shed light on how we moved beyond hoots and grunts to develop vast vocabularies, syntax, and grammar.
The centerpiece of the study is FOXP2, a so-called transcription factor that turns other genes on and off. The gene rose to fame in 2001 when researchers showed that a mutant form of it caused an inherited speech and language problem in three generations of the "KE family" in England. The following year, researchers showed that normal FOXP2 differed by only two amino acids--the building blocks of proteins--between humans and chimpanzees. Analyzing more ancestral species, they further showed that the gene was highly conserved all the way up to chimps, suggesting that it played a prominent role in our unique ability to communicate complex thoughts.
Genes rarely act alone, however, so a team led by neurogeneticist Daniel Geschwind of the University of California, Los Angeles, decided to suss out FOXP2's partners. Geschwind, Genevieve Konopka, who is one of his postdocs, and colleagues first inserted the human and chimp versions of FOXP2 into cells derived from human neurons. In all, they identified 116 genes that were turned on or off differently by human FOXP2 versus chimp FOXP2. The researchers found similar results in brain tissue from both species, they report tomorrow in Nature. The data allowed the team to make complex maps of FOXP2's vast genetic network that revealed other critical interactions (see diagram). "These genes become outstanding candidates for being part of the language circuit," says Geschwind.
A origem da nossa capacidade de falar poderá residir num único gene
11.11.2009 - 18:49 Por Ana Gerschenfeld
Geneticamente, somos muito parecidos com os chimpanzés. Mas há pelo menos uma coisa que nos distingue radicalmente desses nossos “primos”: nós falamos e eles não. Como é que essa profunda transformação surgiu ao longo da evolução?
Pouco se sabe ainda sobre os mecanismos biológicos da emergência da fala. Mas resultados publicados na edição de amanhã da revista Nature por Dan Geschwind, da Universidade da Califórnia, e colegas, sugerem que ela se deverá, em parte, à evolução de um único gene. Mais precisamente: o desenvolvimento da capacidade de falar nos seres humanos modernos, concluem os cientistas, terá começado com umas alterações num gene chamado FOXP2, surgidas depois de o nosso ramo evolutivo se ter separado do dos outros primatas.
Essas alterações no FOXP2, por sua vez, provocaram duas mudanças na proteína fabricada pelo gene, que terão desencadeado uma série de acontecimentos celulares no cérebro humano e levado ao desenvolvimento da fala. “O nosso estudo é o primeiro a analisar o efeito nas células humanas destas [alterações] na proteína FOXP2” diz Geschwind num comunicado.
Researchers have found a gene that could explain why we developed language and speech while our closest living relatives, the chimps, did not.
The gene called FOXP2 is a transcription factor, meaning it regulates other genes. Past research has suggested this gene remained relatively unchanged along mammal evolution until after humans and chimps diverged. And about 200,000 years ago, when modern humans appeared on the scene, scientists think two amino acids (building blocks of proteins) changed in FOXP2.
But whether that amino-acid modification had any real effect on us wasn't known. To find out, a team of researchers expressed the chimp and human forms of this speech gene in neuronal cells that essentially didn't express the gene, or make proteins that carry out that gene's instructions.
They found 116 genes that were expressed differently in humans compared with chimps, suggesting FOXP2 is responsible for those differences, the researchers say.
"We showed that the human and chimp versions of FOXP2 not only look different but function differently too," said study researcher Daniel Geschwind of UCLA. "Our findings may shed light on why human brains are born with the circuitry for speech and language and chimp brains are not."
Why Can't Chimps Speak? Key Differences In How Human And Chimp Versions Of FOXP2 Gene Work
ScienceDaily (Nov. 12, 2009) — If humans are genetically related to chimps, why did our brains develop the innate ability for language and speech while theirs did not?
Scientists suspect that part of the answer to the mystery lies in a gene called FOXP2. When mutated, FOXP2 can disrupt speech and language in humans. Now, a UCLA/Emory study reveals major differences between how the human and chimp versions of FOXP2 work, perhaps explaining why language is unique to humans.
Published Nov. 11 in the online edition of the journal Nature, the findings provide insight into the evolution of the human brain and may point to possible drug targets for human disorders characterized by speech disruption, such as autism and schizophrenia.
"Earlier research suggests that the amino-acid composition of human FOXP2 changed rapidly around the same time that language emerged in modern humans," said Dr. Daniel Geschwind, Gordon and Virginia MacDonald Distinguished Chair in Human Genetics at the David Geffen School of Medicine at UCLA. "Ours is the first study to examine the effect of these amino-acid substitutions in FOXP2 in human cells.
PARIS (AFP) – Two minute changes in a gene that is otherwise identical in humans and chimps could explain why we have full-fledged power of speech while other primates can only grunt or screech, scientists said on Wednesday.
Two tiny changes in the sequence of one gene could have helped install the mechanisms of speech and language in humans.
Pouco se sabe ainda sobre os mecanismos biológicos da emergência da fala. Mas resultados publicados na edição de amanhã da revista Nature por Dan Geschwind, da Universidade da Califórnia, e colegas, sugerem que ela se deverá, em parte, à evolução de um único gene. Mais precisamente: o desenvolvimento da capacidade de falar nos seres humanos modernos, concluem os cientistas, terá começado com umas alterações num gene chamado FOXP2, surgidas depois de o nosso ramo evolutivo se ter separado do dos outros primatas. 
