Forkhead box protein P2

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Forkhead box protein P2
Forkhead box protein P2
Ribbon model of part of the FOXP2 protein in complex with DNA, according to PDB  2A07
Properties of human protein
Mass / length primary structure 715 amino acids
Secondary to quaternary structure Homo- / heterodimer (with FOXP1, FOXP4)
Cofactor Zn 2+
Isoforms 9
Identifier
Gene name FOXP2
External IDs
Occurrence
Parent taxon Vertebrates
Orthologue
human House mouse
Entrez 93986 114142
Ensemble ENSG00000128573 ENSMUSG00000029563
UniProt O15409 P58463
Refseq (mRNA) NM_001172766 NM_001286607
Refseq (protein) NP_001166237 NP_001273536
Gene locus Chr 7: 114.09 - 114.69 Mb Chr 7: 14.9 - 15.44 Mb
PubMed search 93986 114142

Idiogram of the FOXP2 gene. It lies on the q arm (long arm) of chromosome 7 . On the right in blue the 17 exons of FOXP2.

The forkhead box protein P2 (FOXP2) is a transcription factor and belongs to the group of forkhead box proteins . FOXP2 was first discovered in 1998 during an investigation of a London family, in which many relatives suffered from severe language disorders . It is now known that FOXP2 plays a vital role in language acquisition , including grammatical skills.

For the FOXP2 - gene in is mass media , the term "language gene" has been popularized. Many other vertebrates also have this gene, and FOXP2 seems to be crucial for vocal expression in them too. After the gene has been deactivated, for example in mice ( knockout mouse ) or through mutation in humans, it develops a pleiotropic effect: several phenotypic characteristics change.

construction

The FOXP2 gene encodes the FOXP2 protein (see: Genetic Code ).

FOXP2 gene

The human FOXP2 gene is located on chromosome 7 and extends over 603 kb. That is the length of the largest transcript. It consists of 17 exons that are interrupted by introns . The mature mRNA is 6443 bp in length, of which 2220 bp code for the longest isoform of 740 amino acids. Even if the FOXP2 is one of the big genes, it is not uncommon for human genes to consist of over 95% introns.

FOXP2 protein

The FOXP2 protein encoded by the FOXP2 gene consists of 715 amino acids . It is divided into four main areas:

  1. a polyglutamine- rich region that consists of two adjacent polyglutamine regions and is encoded by repeating CAG and CAA sequences,
  2. a zinc finger domain ,
  3. a bZIP domain (“leucine zipper”) and
  4. a forkhead domain formed from amino acids 508 to 584.

The forkhead domain binds to DNA. The zinc finger and bZIP domains are important for protein-protein interactions and are also involved in DNA binding.

function

As a transcription factor, FOXP2 protein is estimated to regulate up to 1,000 other genes; it is still largely unknown which ones. In contrast, there is in-depth knowledge of the effects of a failure of FOXP2.

The FOXP2 protein can already be found in the embryo . It is mainly in the areas expressed that make up later, the cerebellum ( cerebellum ), the thalamus and the basal ganglia develop. The cerebellum and basal ganglia play an important role in learning complex motor skills. Speaking is a skill to which a person has to laboriously learn complex motor skills.

Speech and speech disorders

Video: Why we can talk (including FOXP2)

The FOXP2 gene has a central function in the development of language and speaking skills . This is why mutations in the gene and the associated functional failure of the protein lead to a specific language and speech disorder in humans, especially in articulation and language understanding . A number of known speech and language disorders, as well as autism , are therefore assigned to the region of the FOXP2 gene on chromosome 7.

schizophrenia

Speech disorders are one of the main symptoms of schizophrenia . For this reason, immediately after the discovery of the FOXP2 gene, it was suspected that this gene could play a certain role in the susceptibility to developing schizophrenia. In a comparative study, 186 patients with schizophrenia (according to DSM-IV , they heard strange voices) and 160 healthy volunteers were examined. Specifically, nucleotide polymorphisms of the FOXP2 gene were analyzed. Statistically significant differences in genotype (P = 0.007) and allele frequencies (P = 0.0027) between schizophrenic patients with auditory hallucinations and the control group were found in the individual nucleotide polymorphism rs2396753. The result allows the conclusion that the FOXP2 gene can have an influence on the development of schizophrenia.

discovery

The KE family tree
silent , missense , nonsense and readthrough mutations

In 1990 British geneticists from the Institute of Child Health described an inherited language disorder that affects three generations of a family. About half of the 30 family members have significant problems with grammar , sentence structure and vocabulary . In the scientific literature, this group is referred to as the KE family . She lives in south London and is of European descent. In 1998, the British geneticist Anthony Monaco from Oxford University and his research group discovered a segment on chromosome 7 in family members affected by the language disorder, which he linked to the family's language problems. Genetic examinations of the KE family and a boy (“patient CS”) who is not related to the KE family, but still has the same symptoms, enabled the so-called “language geneFOXP2 to be identified for the first time.

The mutation in the FOXP2 gene apparently first appeared in the grandmother of the family. Her speech disorders are so severe that even her husband has a hard time deciphering her sentences. All three daughters and one of their two sons also have language difficulties. Ten of the 24 grandchildren show the same symptoms. The other members of the family from the south of London have no communication problems. Manifested in affected members of the KE family disturbance than verbal Entwicklungsdyspraxie ( Engl. Developmental Verbal Dyspraxia or abbreviated DVD ) referred to and under the 10 ICD- arranged code F83 ( "Combined specific developmental disorders"). A suitable German paraphrase is inability to articulate speaking .

Symptoms of a FOXP2 Mutation

Verbal developmental dyspraxia

The location of the Broca and Wernicke areas in the cortex

The general behavioral phenotype of those affected by verbal developmental dyspraxia is shown in simple word repetition tests. Words (for example: murderer ) and non-words (for example: Redröm ) must be repeated after suggestions. The subjects affected by the mutation have significantly greater problems with articulation than those not affected. The impairment increases gradually with the complexity of the words to be articulated.

Orofacial dyspraxia

The affected persons have difficulty in voluntary control of the facial muscles ; a symptom called orofacial dyspraxia . These difficulties cannot be attributed to a general impairment of motor skills, since the motor performance of the patient's extremities is indistinguishable from normal individuals. The hearing ability of the patient is also normal. The DVD phenotype is similar to that seen in patients with Broca's aphasia . However, there are important behavioral differences between the two pathologies . Thus aphasic in the word retest significantly better than in the non-word repetition. In contrast, the members of the KE family affected by the FOXP2 mutation are equally bad in both tests. One possible explanation for this is that aphasia sufferers learned to associate sound formation patterns with the corresponding word meanings before their disease broke out. In contrast, the affected members of the KE family never had the opportunity to learn word articulation patterns. Therefore they inevitably fail to solve the tasks of the word repetition test with the word meanings.

More symptoms

In addition to verbal and orofacial dyspraxia, members of the KE family affected by the mutation do significantly worse than their unaffected relatives on tests that measure receptive (understanding of language) and grammatical production skills. The deficit includes the inability to properly inflect words or form sentences to easily relate objects to their corresponding images. In addition, the subjects affected showed significantly lower intelligence in non-verbal intelligence tests ( IQ average value: 86, range: 71–111) than those who were not affected (IQ average value: 104, range: 84–119). There is a significant overlap between the two groups.

Effects of changes to FOXP2

The autosomal dominant inheritance
Horizontal section through the forebrain. The basal ganglia in blue.

The disorders caused by the mutation are inherited as an autosomal dominant trait . The FOXP2 gene is located on the long arm (q arm) of chromosome 7 in band 7q31. The gene was originally named "SPCH1" (from Speech 1 ) when only the affected chromosome could be identified .

In a 2006 screening of 49 test persons suffering from verbal dyspraxia, a maternal nonsense mutation was found in one test person and an allegedly missense mutation in the FOXP2 gene in two test persons. These results suggest that FOXP2 mutations are a relatively rare cause of speech and language disorders.

Exon 14 (KE family)

The KE family members affected by the hereditary disease have a missense - point mutation in exon 14 of the gene. The nucleobase guanine has been replaced by adenine at one point . As a result, the amino acid histidine is incorporated into position 553 of the FOXP2 protein instead of the amino acid arginine . In the one -letter code , R is the designation for arginine and H for histidine  . The mutation is therefore called R553H. The protein formed can no longer perform its functions as a result of the exchange of the amino acid.

By means of imaging techniques of brain by members of the KE family were abnormalities in the caudate nucleus , a part of the basal ganglia found. First insights into the neural basis could be obtained with the help of functional magnetic resonance imaging of the brain. The KE family members affected by the mutation had bilateral structural deficits. These were mainly shown in a reduced density of gray matter ("gray cells") in the area of ​​the caudate nucleus of the basal ganglia , the anterior cerebellum and Broca's area . In contrast, an abnormally high density of gray matter was found in the putamen and Wernicke's area in these patients . Interestingly , the volume of the caudate nucleus correlates very well with the performance shown in the language test. This is an indication of the influence of the caudate nucleus on the pathology of verbal developmental dyspraxia (DVD).

The basal ganglia play a crucial role in movement planning and sequencing. Structural deviations in the striatal regions of the basal ganglia ( nucleus caudatus and putamen) therefore generally mean an impairment of the control of the orofacial motor function (oral motor function). In contrast, it is unclear why the oral motor skills are specifically impaired without other motor functions being affected.

Exon 7 ( nonsense mutation)

In 2005, a so-called nonsense mutation was also discovered in the FOXP2 gene in children who do not belong to the KE family but also suffer from verbal dyspraxia . A nonsense mutation is a mutation that disfigures the meaning and results in a stop codon , i.e. a base triplet that leads to the synthesis of the protein being terminated at this point. In these cases with a nonsense mutation, too, the language and speech deficits can be traced back to the mutation.

Break point between exon 3b and 4

A patient, referred to in the specialist literature as patient CS , has a balanced translocation between one copy of chromosomes 5 and 7 (t (5; 7) (q22; q31.2)). The breakpoint on chromosome 7 lies in the FOXP2 gene between exons 3b and 4 and thus affects all known isoforms of the FOXP2 protein. This patient also suffers from symptoms similar to those of the members of the KE family affected by the mutation.

Gene deletion

In 2006, a Canadian girl was found to have lost ( deletion ) parts of chromosome 7 in bands 7q31 and 7q32. The missing area includes the FOXP2 gene. The child has serious communication disorders in the form of orofacial dyspraxia, a marked deformity and a lag in their general development. She cannot cough, sneeze, or laugh spontaneously.

In mice

Two knockout mice

In an animal experiment, the two exons 12 and 13 of Foxp2 were switched off (“knockout”) in mice . If both copies of the Foxp2 genes were interrupted, this led to severe motor disorders, premature death, and failure to communicate using ultrasound. The latter can usually be triggered by removing the young from their mother. If, on the other hand, only one of the two Foxp2 genes was interrupted, this caused a slight delay in the development of the animals and a significant change in communication by means of ultrasound. Abnormal changes in the cerebellum, especially the Purkinje cells - the ganglion cells of the stratum gangliosum of the cerebellar gyri  - were found in the animals .

When the human variant of the gene was implanted in the genome of mice, they showed a significant improvement in learning ability compared to unchanged animals. Changes in the basal ganglia of the modified mice were found.

In zebra finches

Zebra finch ( Taeniopygia guttata )

The language learning is not limited to humans. Some animal species, including whales , bats and birds from three orders, can learn their acoustic communication ("animal language") through imitation. Songbirds communicate through a song that they largely have to learn. They acquire their sound sequences by imitating older conspecifics. Young animals raised in isolation by conspecifics, on the other hand, remain silent. Songbirds are therefore suitable as animal models for studies of language acquisition and its genetic predisposition . In many other animal species the utterances are innate. Even monkeys are believed to have an innate repertoire of sounds.

The song of the zebra finch ( Taeniopygia guttata ) consists of different syllables that result in structured sequences. The part of the brain that is important for language acquisition in humans lies in the basal ganglia. In songbirds this area is Area X called. The expression of Foxp2 in Area X is highest during the song learning phase in the zebra finch. In canaries, however , Foxp2 is expressed seasonally differently. It is particularly strongly expressed in phases in which the singing is changed. Comparable changes in Foxp2 expression could not be found in bird species that do not learn how to sing, such as wood pigeons .

With the help of RNA interference , employees of the Max Planck Institute for Molecular Genetics in Berlin-Dahlem switched off the Foxp2 gene in Area X of zebra finches. In this process, short, complementary stretches of RNA are introduced into the cells, where they intercept the mRNA and suppress the production of the FOXP2 protein. The zebra finches, in which Foxp2 was switched off, imitated the syllables of their older conspecifics less precisely and left out entire syllables when singing.

The exact mechanism of action of Foxp2 is not yet known. In principle, the genetic defect can affect the motor functions, for example of the vocal head , or the storage of the chants to be learned.

The molecular evolution of FOXP2

Family tree of FOXP2 in primates with the mouse as a comparison group. The first digit of a pair of numbers indicates the number of changed amino acids ( missense mutations), the second the number of silent mutations. In the case of silent mutations, the base sequence on the DNA changes, but the same amino acid is encoded (see wobble hypothesis ). Since silent mutations are therefore subject to considerably less selection pressure , they are usually more common than missense mutations; however, this does not apply to the human line of development.

FOXP2 in mammals and other vertebrates

The FOXP2 protein is one of the most highly conserved proteins in mammals; it differs only very slightly between the individual species. Exceptions are different families of bats . There, significant differences in the FOXP2 sequence were found. In contrast, almost identical FOXP2 proteins can be found in songbirds , fish and reptiles , for example .

Gene segments that code for polyglutamine are generally known to have relatively high mutation rates. This is also the case with the two polyglutamine regions of the FOXP2 gene. All the taxa examined had different polyglutamine lengths. The polyglutamine area plays a very subordinate role in the function of the FOXP2 protein. If these regions are disregarded, the human FOXP2 protein differs from the mouse ortholog by only three amino acids.

The lines of evolution that lead to humans and mice divided about 40 million years ago. The last common ancestor of the chimpanzee and humans lived 4.6 to 6.2 million years ago. Of the three amino acid differences between humans and mice, one arose in an ancestor of the mouse, none between the separation of the mouse and primate ancestors until the separation of humans and chimpanzees, and two afterwards (see also figure on the right).

The FOXP2 protein of the orangutan differs from that of the mouse by two amino acids and by three from the human one. There are also only seven amino acid differences between the FOXP2 protein of the zebra finch and humans.

The human ability to speak is based on anatomical and fine motor skills which other primates as closest relatives do not have. Some research groups suggest that the difference in the two amino acids between chimpanzees and humans caused speech development in humans. However, this thesis is controversial, since other working groups could not establish a connection between species with learned vocalization and those with a similar mutation in FOXP2 .

The two differences to the closest human relatives are located in exon 7. In position 303, threonine is exchanged for asparagine and in position 325 asparagine is exchanged for serine . The likely protein structures were determined using simulation calculations. The mutation at position 325 creates a potentially reactive site for phosphorylation by protein kinase C in human FOXP2 protein , along with a small change in the protein's secondary structure. It is known from various studies that the phosphorylation of transcription factors with a forkhead structure can be an important mechanism in gene regulation . To clarify whether the two amino acids encoded in exon 7 are polymorphic in humans , this exon was sequenced in 44 people from different continents. In no case was any form of amino acid polymorphism found.

Bats

Bats, in the picture a Townsend long-eared ( Corynorhinus townsendii ), have the ability to echolocate
Flying foxes, in the picture a golden crowned flying fox (
Acerodon jubatus ), are not capable of echolocation

While systematic DNA sequencing in most mammals revealed an extremely low rate of mutation on the FOXP2 gene, only affecting a few amino acids, considerable differences were found in some bat species. The bats are one of the few vertebrates that have the ability to learn sounds.

The order of the bats ( Chiroptera ) consists of two suborders: the flying foxes ( Megachiroptera ) and the bats ( Microchiroptera ). Bats use echolocation for orientation and for catching prey. With them are sensorimotor skills particularly well developed. The reception of the emitted ultrasound sounds requires a pronounced aural (hearing-related) and - depending on the bat species - orofacial (mouth) or nasofacial (nose) coordination. In contrast, fruit bats do not have the ability to echolocate.

In the DNA sequencing, the two exons 7 and 17 were identified as the areas in which - depending on the bat species - the greatest variability of the Foxp2 gene was present. There were considerable differences between the Foxp2 structure of bats and fruit bats. The data suggest that changes in the Foxp2 gene were critical in the development of echolocation in bats.

FOXP2 in paleogenetics

With the help of paleogenetics it was first calculated that the gene variant of FOXP2 that is widespread in humans today is between 100,000 and a maximum of 200,000 years old. This period was determined in a mathematical model in which the mutations on introns were specifically considered. Introns are functionless components of genes for protein synthesis. Since they have no direct significance for the structure of the proteins, a significantly higher mutation rate can be observed in them than in exons. The history of a gene can be reconstructed from this mutation rate. The calculated period would coincide well with the “birthday” of the human species, dated by paleoanthropologists . In terms of evolutionary history, this is significantly later than the point in time when the evolutionary family tree split between Homo sapiens and Homo neanderthalensis , which was also determined by paleogenetics , about 300,000 to 400,000 years ago. From this data it was therefore initially concluded that the Neanderthals did not have the human language ability.

Some anthropologists argue that the rapid spread of the FOXP2 gene, which is essential for language acquisition, supports the thesis that language was the driving force behind the spread of humans on earth.

The thesis about the age of today's FOXP2 gene variant in humans and derived from the fact that the Neanderthals therefore did not have the human language ability had to be revised in October 2007. The FOXP2 gene was sequenced from Neanderthal bones . No difference was found in the sequence of the Neanderthal compared to modern humans.

The DNA sequencing of prehistoric finds is a very laborious process. The samples contain only very small amounts of endogenous DNA. In addition, the contamination of the samples and reagents with human DNA is a significant problem, especially because the DNA of Neanderthals differs little from that of modern humans. From two different Neanderthal bones in the 2006 Asturian El Sidrón cave was found, which was first mitochondrial DNA (mtDNA) analysis of 43,000-year-old samples. With the help of the mtDNA, some known substitutions can be used to determine whether it is the DNA of a modern human or a Neanderthal. After it was established that the samples clearly contained the DNA of a Neanderthal man, the two areas of exon 7 of the FOXP2 gene that have been known to be mutations since the split in humans and chimpanzees were examined. No difference was found in the corresponding sequence of the Neanderthals and that of modern humans. The Neanderthals thus also had the language-enabling mutation of the FOXP2 gene. The possibility that the gene was established by children of Homo sapiens and Homo neanderthalensis in both modern humans and Neanderthals is excluded based on the results of studies on mitochondrial DNA.

literature

Technical article

Textbooks and university publications

Popular science

Web links

Commons : FOXP2  - collection of images, videos and audio files

Individual evidence

  1. Homologues at OMA
  2. a b c L. Feuk u. a .: Absence of a Paternally Inherited FOXP2 Gene in Developmental Verbal Dyspraxia. In: American Journal of Human Genetics. Volume 79, 2006, pp. 965-972, PMID 17033973 .
  3. P. Schlobinski: Grammar Models: Positions and Perspectives. Vandenhoeck & Ruprecht, Göttingen 2003, ISBN 3-525-26530-1 , pp. 83-84.
  4. Ensembl Gene Report for ENSG00000128573 . Ensembl.org, accessed December 29, 2015
  5. ^ AF Wright, N. Hastie: Genes and Common Diseases: Genetics in Modern Medicine. Cambridge University Press, Cambridge 2007, ISBN 0-521-83339-6 .
  6. J. Zhang et al. a .: Accelerated Protein Evolution and Origins of Human-Specific Features: FOXP2 as an Example. In: Genetics. Vol. 162, 2002, pp. 1825-1835, PMID 12524352 .
  7. EH McConekey: How the Human Genome works. Jones & Bartlett, Sudbury (Mass.) 2004, ISBN 0-7637-2384-3 , p. 5.
  8. a b c d e W. Enard u. a .: Molecular evolution of FOXP2, a gene involved in speech and language. In: Nature , 2002, 418, pp. 869-872, PMID 12192408 doi: 10.1038 / nature01025
  9. a b c K. D. MacDermot et al. a .: Identification of FOXP2 Truncation as a Novel Cause of Developmental Speech and Language Deficits. In: American Journal of Human Genetics. Volume 76, 2005, pp. 1074-1080, doi: 10.1086 / 430841 , PMID 15877281 .
  10. U. Wahn (Ed.): Pediatric Allergology and Immunology. 4th, revised and expanded edition, Elsevier, Munich 2005, ISBN 3-437-21311-3 , p. 895.
  11. a b c S. Haesler: Thus spoke the zebra finch. ( Memento of the original from March 4, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF; 172 kB) In: Brain & Spirit , 12/2006, pp. 52–57. @1@ 2Template: Webachiv / IABot / www.bcp.fu-berlin.de
  12. Chatty zebra finches. Press release of the Max Planck Society, March 31, 2004 (PDF)
  13. ^ EK O'Brien et al. a .: Association of Specific Language Impairment (SLI) to the Region of 7q31. In: Am. J. Hum. Genet. , 72/2003, pp. 1536-1543, PMID 12721956
  14. ^ TH Wassink u. a .: Evaluation of FOXP2 as an autism susceptibility gene. In: American Journal of Medical Genetics. Volume 114, 2002, pp. 566-569, PMID 12116195 .
  15. J. Sanjuán et al. a .: Association between FOXP2 polymorphisms and schizophrenia with auditory hallucinations. In: Psychiatric Genetics. Volume 16, 2006, pp. 67-72, PMID 16538183 .
  16. a b c S. E. Fisher et al. a .: Localization of a gene implicated in a severe speech and language disorder. In: Nature Genetics . Volume 18, 1998, pp. 168-170, PMID 9462748 .
  17. M. Gopnik: Feature-blind grammar and dysphasia . In: Nature . No. 344 , 1990, pp. 715 , doi : 10.1038 / 344715a0 .
  18. J. Cohen: The Evolution of Language . In: Technology Review . No. 2 , 2008.
  19. A. Wilcke, C. Ligges, J. Burkhardt, M. Alexander, C. Wolf, E. Quente, P. Ahnert, P. Hoffmann, A. Becker, B. Müller-Myhsok, S. Cichon, J. Boltze , H. Kirsten: Imaging genetics of FOXP2 in dyslexia. In: European journal of human genetics: EJHG. Volume 20, number 2, February 2012, ISSN  1476-5438 , pp. 224-229, doi: 10.1038 / ejhg.2011.160 . PMID 21897444 , PMC 3260915 (free full text).
  20. U. Bahnsen, U. Willmann: How genes pursue their lips. In: The time . No. 51, 2001.
  21. a b c d e K. E. Watkins et al. a .: Behavioral analysis of an inherited speech and language disorder: comparison with acquired aphasia. In: Brain. Volume 125, 2002, pp. 452-464, PMID 11872604 .
  22. ^ AR Damasio, N. Geschwind: The neural basis of language. In: Annual Review of Neuroscience. Volume 7, 1984, pp. 127-147.
  23. a b c d e S. Haesler: Studies on the evolution and function of the FoxP2 gene in songbirds. Dissertation, FU Berlin, 2007
  24. KJ Alcock et al. a .: Oral dyspraxia in inherited speech and language impairment and acquired dysphasia. In: Brain and language. Volume 75, 2000 , pp. 17-33, PMID 11023636 .
  25. a b F. Vargha-Khadem u. a .: Neural basis of an inherited speech and language disorder. In: Proceedings of the National Academy of Sciences of the United States of America . Volume 95, 1998 , pp. 12695-12700, PMID 9770548 .
  26. E. Belton et al. a .: Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia. In: Human Brain Mapping. Volume 18, 2003, pp. 194-200, PMID 12599277 .
  27. ^ AM Graybiel: Building action repertoires: memory and learning functions of the basal ganglia. In: Current Opinion in Neurobiology. Volume 5, 1995, pp. 733-741, PMID 8805417 .
  28. P. Markl: Why do people speak? - The latest findings in the search for a “language gene” . ( Memento from December 7, 2008 in the Internet Archive ) In Wiener Zeitung . September 13, 2002.
  29. S. Zeesman u. a .: Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2. In: American Journal of Medical Genetics. Volume 140, 2006, pp. 509-514, PMID 16470794 .
  30. W. Shu, JY Cho et al. a .: Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene. In: PNAS. Volume 102, Number 27, July 2005, pp. 9643-9648, ISSN  0027-8424 . doi: 10.1073 / pnas.0503739102 . PMID 15983371 . PMC 1160518 (free full text).
  31. E. Fujita, Y. Tanabe et al. a .: Ultrasonic vocalization impairment of Foxp2 (R552H) knock-in-mice related to speech-language disorder and abnormality of Purkinje cells. In: PNAS. Volume 105, Number 8, February 2008, pp. 3117-3122, ISSN  1091-6490 . doi: 10.1073 / pnas.0712298105 . PMID 18287060 . PMC 2268594 (free full text).
  32. C. Schreiweis, Ann M. Graybiel et al. a .: Humanized Foxp2 age learning in differently balanced cortico-basal ganglia circuits (abstract). In: Neuroscience. 2011, Washington, April 12-16 November 2011.
  33. FOXP2. “Sprachgen” also helps with learning . In: Wissenschaft-online.de , November 23, 2011.
  34. S. Haesler et al. a .: FoxP2 expression in avian vocal learners and non-learners. In: Journal of Neuroscience. Volume 24, 2004, pp. 3164-3175, PMID 15056696 .
  35. SA White et al. a .: Singing Mice, Songbirds, and More: Models for FOXP2 Function and Dysfunction in Human Speech and Language. In: The Journal of Neuroscience. Volume 26, 2006, pp. 10376-10379, PMID 17035521 .
  36. Max Planck Society: Bad singing students - Scientists mute the FOXP2 gene in zebra finches and hear something. Press release of December 4, 2007
  37. S. Haesler et al. a .: Incomplete and inaccurate vocal imitation after knockdown of FoxP2 in songbird basal ganglia nucleus Area X. In: PLOS Biology . Volume 5, 2007, e321, PMID 18052609 .
  38. a b G. Li u. a .: Accelerated FoxP2 evolution in echolocating bats. In: PLoS ONE . Volume 2, 2007, e900, PMID 17878935 .
  39. ^ A b D. M. Webb, J. Zhang: FoxP2 in song-learning birds and vocal-learning mammals. In: J Hered. , 96/2005, pp. 212-216, PMID 15618302
  40. ^ A b C. Scharff, S. Haesler: An evolutionary perspective on FoxP2: strictly for the birds? In: Current Opinion in Neurobiology. Volume 15, 2004, pp. 694-703, PMID 16266802 .
  41. ^ S. Kumar, SB Hedges: A molecular timescale for vertebrate evolution. In: Nature. Volume 392, 1998, pp. 917-920, PMID 9582070 .
  42. E. Eizirik et al. a .: Molecular dating and biogeography of the early placental mammal radiation. In: Journal of Heredity. Volume 92, 2001, pp. 212-219, PMID 11396581 .
  43. FC Chen, WH Li: Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees. In: American Journal of Human Genetics. Volume 68, 2001, pp. 444-456, PMID 11170892 .
  44. I. Teramitsu u. a .: Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction. In: Journal of Neuroscience. Volume 24, 2004, pp. 3152-3163, PMID 15056695 .
  45. S. Haesler et al. a .: FoxP2 expression in avian vocal learners and non-learners. In: Journal of Neuroscience. Volume 24, 2004, pp. 3164-3175, PMID 15056696 .
  46. ^ P. Liebermann: The Biology and Evolution of Language. Harvard University Press, Cambridge (Mass.) 1984, ISBN 0-674-07413-0 .
  47. W. Enard et al. a. Molecular evolution of FOXP2, a gene involved in speech and language. In: Nature. Volume 418, 2002, pp. 869-872, PMID 12192408 .
  48. GJ Kops u. a .: Control of cell cycle exit and entry by protein kinase b-regulated forkhead transcription factors. In: Molecular and Cellular Biology. Volume 22, 2002, pp. 2025-2036, PMID 11884591 .
  49. A. Brunet et al. a. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. In: Cell . Volume 96, 1999, pp. 857-868, PMID 10102273 .
  50. JW Boughman: Vocal learning by greater spear-nosed bats. In: Proceedings of the Royal Society B: Biological Sciences. Volume 265, 1998, pp. 227-233, PMID 9493408 .
  51. ^ G. Jones, RD Ransome: Echolocation calls of bats are influenced by maternal effects and change over a lifetime. In: Proceedings of the Royal Society B: Biological Sciences. Volume 252, 1993, pp. 125-128, PMID 8391702 .
  52. CF Moss, SR Sinha: Neurobiology of echolocation in bats. In: Current Opinion in Neurobiology. Volume 13, 2003, pp. 751-758, PMID 14662378 .
  53. Paleogenetics: How old is the language? In: Geo Magazin , 10/2002
  54. ^ U. Bahnsen: Palaeogenetics: Guitarist in the genetic laboratory. In: time knowledge. Issue 34, 2002
  55. ^ RG Klein: The Human Career: Human Biological and Cultural Origins. University Chicago Press, Chicago 1989, ISBN 0-226-43963-1 .
  56. ED Jarasch: Genetic traces of the incarnation. ( Memento from December 6, 2008 in the Internet Archive ) BIOPRO Baden-Württemberg GmbH.
  57. J. Müller-Jung; in: Frankfurter Allgemeine Zeitung , August 15, 2002
  58. F. Carmine: Genome Technology and Stem Cell Research - a Responsible Risk? Govi-Verlag, Eschborn 2003, ISBN 3-7741-1000-X , p. 53.
  59. M. Inman: Neandertals Had Same "Language Gene" as Modern Humans. In: National Geographic News. October 18, 2007.
  60. a b J. Krause u. a .: The derived FOXP2 variant of modern humans was shared with Neandertals. In: Current Biology. Volume 17, 2007, pp. 1908-1912, doi: 10.1016 / j.cub.2007.10.008 , PMID 17949978 .
  61. M. Hofreiter u. a .; Ancient DNA. In: Nature Reviews Genetics . Volume 2, 2001, pp. 353-359, PMID 11331901
  62. S. Pääbo: Human evolution. In: Trends in Cell Biology . Volume 9, 1999, M13-16, PMID 10611673 .
  63. A. Rosas et al. a .: Paleobiology and comparative morphology of a late Neandertal sample from El Sidron, Asturias, Spain. In: Proceedings of the National Academy of Sciences USA. Volume 103, 2006, pp. 19266-71, PMID 17164326 .
  64. RE Green u. a .: Analysis of one million base pairs of Neanderthal DNA. In: Nature , 444/2006, pp. 330-336, PMID 17108958
  65. Neanderthals have language genes. ( Memento of the original from January 26, 2017 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. In: Archaeologie-online.de , October 19, 2007 @1@ 2Template: Webachiv / IABot / www.archaeologie-online.de
This article was added to the list of excellent articles on August 11, 2008 in this version .