The story starts in 2001, when scientists identified a critical gene found in all vertebrates. Dubbed FOXP2, for "forkhead box protein P2," the "transcription factor" gene's role is to turn the expression of other genes up or down, on or off - the genetic equivalent of a light dimmer.
FOXP2 was discovered during a study of a family in England, three generations of whom suffered from severe speech and language problems. When the family members were found to carry a mutant version of the same gene, it was surmised the gene was important to speech and language development. It was later discovered that the human version of FOXP2 differed by just two amino acids out of a sequence of hundreds, from FOXP2 in chimps, our closest relatives.
Now, a study by scientists at UCLA and Emory University shows human FOXP2 and chimp FOXP2 turn on and off a very different selection of genes.
"We knew that the amino acids in the human version of FOXP2 were different from those in the chimp version," says Genevieve Konopka, postdoctoral fellow in neurology at the David Geffen School of Medicine at UCLA and lead author of the study, which was partly funded by NARSAD.
"We knew that the evolution in the gene happened about the time that language occurred" - roughly two hundred thousand years ago. "We wanted to test the hypothesis that the human version of FOXP2 functioned differently from the chimp version." Working with Dr. Daniel Geschwind, Gordon and Virgina MacDonald Distinguished Chair in Human Genetics, and professor of neurology and psychiatry at the UCLA School of Medicine, the team put the two strains of FOXP2 in cell cultures and studied them. If the two-amino-acid difference between human and chimp FOXP2 was really important, then changing them would show some change in function.
It did.
" Among the genes affected differently: Those controlling the motor aspect of language; cranial facial development (patients with FOXP2 mutations may exhibit cranial facial defects, such as cleft palate); and development of the nervous system.
This seems to build the case that the inability of chimps to speak may be due to differences both neurological and mechanical: That is, they lack our motor-planning and speech sequencing ability, say, as well as the facial structure - dynamics of the larynx, throat or palate - also crucial to human speech.
"If you mutate this gene, you don't get a pure linguistic disorder or a pure motor speech disorder," says Dr. Geschwind. "Aspects of syntax are affected, and parts of the physical structure are affected. In severe cases, patients [speaking] are nearly incomprehensible."
Possible Role in Alzheimer's, Schizophrenia, Autism?
As crucial as FOXP2 is to speech and language development, it is clearly not the only factor. "FOXP2 causes one percent of developmental dysphasia, a developmental spoken language disorder," says Dr. Geschwind. "What causes the other ninety-nine percent?"
The more we learn more about FOXP2's role in human brain development, the more we may learn about diseases to which humans are uniquely vulnerable, such as Alzheimer's, Parkinson's, schizophrenia and autism. (A connection has already been established between FOXP2 and the latter two conditions.)
"The opportunity for further discoveries about language and other brain development rests on modeling but also on doing comparative research using actual tissue of chimpanzees, our closest relatives," says Todd Preuss, neuroanatomist at Emory University's Yerkes National Primate Research Center, who worked with chimp tissue for the UCLA study.
"This study is part of the story of language acquisition but it's probably much more than that. And if you want to understand human brain specialization, it helps to compare it to chimpanzees" - not to rodents, the usual stand-in. Preuss's lab is one of only two in the world, at this level, that works with chimpanzee tissue, and the imminent extinction of the species in the wild makes his lament all the more urgent.
"Our children's generation may be the last one to see chimpanzees," says Preuss. "And to answer questions about human brain development, you need to do comparative work.
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