Download Lilach Goren

Talk of Genetics
Lilach Goren
January 2009
Thanks: Benny Gil,Yehudit Hasin
Genetics of Talk
Lilach Goren
neuroscience
evolution
sociology
genetics
informatics
linguistics
philosophy
psychology
anthropology
Thanks: Benny Gil,Yehudit Hasin
many question marks
•
•
•
•
•
How important is language in the development of human society?
What defines language? How are other species different?
What language abilities are innate?
Do we have specific language genes?
What is the relation of genes to the brain activity related with
language?
2
Outline
•
•
•
Language faculty - nature or nurture?
The language of genes
A gene for language?
•
•
•
•
Specific Language Impairment and the KE case study
Evolution of the FOXP2 gene
?‫מותר האדם‬
Summary
3
Language faculty - nature or nurture?
“man has an instinctive tendency to speak, as we see in
the babble of our young children”
C. Darwin, “Decent of Man” (1871)
• learning a language is an instinct, much like having sex
• nature gives the tools, nurture allows the development
• human language is qualitatively different: “discrete infinity”
N. Chomsky, Language and problems of knowledge (1988)
Is there a gene encoding language abilities?
4
The language of genes
human:
22 pairs of autosomal chromosomes
1 pair of sex chromosomes
exon: the coding parts of the gene
intron: non-coding parts of the gene
5
The language of genes
human:
22 pairs of autosomal chromosomes
1 pair of sex chromosomes
exon: the coding parts of the gene
intron: non-coding parts of the gene
transcription factor:
A protein that binds to a specific
DNA sequence controlling the
transcription of genetic info. from
DNA to RNA
5
The language of genes
Allele for purple flowers
locus for flowercolour gene
homologous pair
of chromosomes
Allele for white flowers
6
The language of genes
dominant trait
phenotype:
The observable trait
Allele for purple flowers
locus for flowercolour gene
homologous pair
of chromosomes
Allele for white flowers
recessive trait
6
The language of genes
mutation:
DNA variation that codes for a different protein
(must be on exons)
Human1
Human2
Human3
Human4
Human5
Human6
CGC
CGC
CGC
CGC
CGC
CGC
TAT
TAT
TAC
TAT
TAT
TAT
TCC
TCC
TCC
TCC
TCC
TCC
CCG
CAG
CCG
CAG
CCG
CCG
ATT
ATT
ATT
ATT
ATT
ATT
CAG
CAG
CAG
CAG
CAG
CAG
AAT
AAT
AAT
AAT
AAT
AAT
GCC
GCA
GCA
GCC
GCC
GCC
CAG
CAG
CAG
CAG
CAG
CGC
silent mutation:
DNA change that is not expressed
7
A gene for language?
Hurst et al. (1990)
KE family
all or none
male and female
not environment!
hypothesis: single autosomal-dominant gene for SLI
8
Specific Language Impairment
Gopnik and Crago (1991)
Every day I plam;
yesterday I ________.
This is a wug
Now there is another one.
There are two of them.
These are two _________.
one zat, many ______
one sas, many ______
one zoop, many ______
one tob, many ______
9
Specific Language Impairment
Gopnik and Crago (1991)
Every day I plam;
yesterday I ________.
This is a wug
Now there is another one.
There are two of them.
These are two _________.
wugness
one zat, many ______
zackle
one sas, many ______
sasses
one zoop, many zoopes
______
one tob, many ______
tobyees
9
Specific Language Impairment
symptoms:
1. fine orofacial movement difficulty
2. word inflections
3. syntax structures
4. can memorize, not deduce rules
5. don’t have a hearing or articulation problems at older age
6. mean non-verbal IQ < unaffected
7. some have normal IQ
There are very specific language problems, is there a specific origin?
10
A gene for language?
specific region on chromosome 7 has a role in causing SLI in the KE family.
Fisher et al. Nature Genet. 18, 168 (1998)
SLI in an unrelated person CS helps to identify a specific gene, FOXP2.
Lai et al. Nature 413, 519(2001)
Chr 7
7q31
N
FOXP2 gene
CS mutation: translocation
silent
re
11
A gene for language?
specific region on chromosome 7 has a role in causing SLI in the KE family.
Fisher et al. Nature Genet. 18, 168 (1998)
SLI in an unrelated person CS helps to identify a specific gene, FOXP2.
Lai et al. Nature 413, 519(2001)
Chr 7
7q31
N
FOXP2 gene
CS mutation: translocation
locate encoding sequence
silent
re
11
A gene for language?
specific region on chromosome 7 has a role in causing SLI in the KE family.
Fisher et al. Nature Genet. 18, 168 (1998)
SLI in an unrelated person CS helps to identify a specific gene, FOXP2.
Lai et al. Nature 413, 519(2001)
Chr 7
7q31
N
FOXP2 gene
CS mutation: translocation
locate encoding sequence
silent
re
identify a protein in brain
11
A gene for language?
specific region on chromosome 7 has a role in causing SLI in the KE family.
Fisher et al. Nature Genet. 18, 168 (1998)
SLI in an unrelated person CS helps to identify a specific gene, FOXP2.
Lai et al. Nature 413, 519(2001)
Chr 7
7q31
N
FOXP2 gene
CS mutation: translocation
locate encoding sequence
silent
re
identify a protein in brain
FOX motif - transcription factor
11
A gene for language?
Lai et al. Nature 413, 519(2001)
Chr 7
7q31
FOXP2 gene
1. KE mutation: G A
nucleotide transition at forkhead
2. The same mutation on all
affected members!
si
Arginine
Histidine
3. No mutation in 364
chromosomes from unaffected
12
FOXP2 - a transcription factor
Lai et al. Nature 413, 519(2001)
• Forkhead domain is the binding area to the DNA
• Mutation in it disrupts DNA binding
• During embryo development: damage to brain structures
• Many FOX proteins are regulators of embryogenesis
• Mutations of the forkhead domain related to specific human disorders
FOXP2 is a gene related to specific language abilities
13
Evolution of the FOXP2 gene
Enard et al. Nature 418, 869 (2002)
715 amino acids
human
FOXP2 is
among the 5%
most conserved
proteins
chimpanzee
mouse
exon 7
allows phosphorylation
transcription regulation
14
since the fixation of the beneficial allele is 0, with approximate 95%
confidence intervals of 0 and 120,000 years. Our point-estimate of 0
Evolution of the FOXP2 gene
- 70 Myr
- 5 Myr
0
2/0***
Human
0/2
0/7
0/5
0/2
C himp
0/2
G orilla
1/2
silent mutation
(neutral)
Orang-utan
0/5
Rhesus
1/131
Mouse
amino
acid mutation
Figure 2 Silent and
replacement
nucleotide substitutions mapped on a phylogeny of
primates. Bars represent nucleotide changes. Grey bars indicate amino-acid changes.
NATURE | VOL 418 | 22 AUGUST 2002 | www.nature.com/nature
located
Model
A summ
since th
summa
selectiv
polymo
selectio
propor
(here, n
spaced
of obta
are in t
size of h
is not c
assumi
that on
estimat
human
rate pe
parame
polymo
© 2002 Nature Publishing
15
since the fixation of the beneficial allele is 0, with approximate 95%
confidence intervals of 0 and 120,000 years. Our point-estimate of 0
Evolution of the FOXP2 gene
- 70 Myr
- 5 Myr
common ancestor
0
2/0***
Human
0/2
0/7
0/5
0/2
C himp
0/2
G orilla
1/2
silent mutation
(neutral)
Orang-utan
0/5
Rhesus
1/131
Mouse
amino
acid mutation
Figure 2 Silent and
replacement
nucleotide substitutions mapped on a phylogeny of
primates.
Bars represent
nucleotide(5changes.
Grey
amino-acid changes.
2 replacement
in human
Myr) vs.
70bars
Myrindicate
- no constraint
relaxation
located
Model
A summ
since th
summa
selectiv
polymo
selectio
propor
(here, n
spaced
of obta
are in t
size of h
is not c
assumi
that on
estimat
human
rate pe
parame
polymo
•
inAUGUST
amino 2002
acids
in 226 human chromosomes
• No variation
© 2002 Nature Publishing
NATURE
| VOL 418 | 22
| www.nature.com/nature
15
Selective sweep
A T C G C
ancestor
A T C G C
A T C G C
A T A G C
A T A G C
A T C G C
A T C G C
A T C G T
A T C G T
G T C G C
G T C A C
G T C G C
G T C G C
neutral
variation
Human1
Human2
Human3
Human4
Human5
Human6
16
Selective sweep
AA TT CC GG CC
ancestor
AA TT CC GG CC
AA TT CC GG CC
AA TT AA GG CC
AA TT AA GG CC
AA TT CC GG CC
AA TT CC GG CC
AA TT CC GG TT
AA TT CC GG TT
GG TT CC GG CC
GG TT CC AA CC
GG TT CC GG CC
GG TT CC GG CC
neutral
variation
Human1
Human2
Human3
Human4
Human5
Human6
advantageous
mutation
16
Selective sweep
AA TT CC GG CC
ancestor
AA TT CC GG CC
AA TT CC GG CC
G T C A C
G T C A C
AA TT AA GG CC
AA TT AA GG CC
G T C A C
G T C A C
AA TT CC GG CC
AA TT CC GG CC
G T C A C
G T C A C
AA TT CC GG TT
AA TT CC GG TT
G T C A C
G T C A C
GG TT CC GG CC
GG TT CC AA CC
G T C A C
A T C A C
GG TT CC GG CC
GG TT CC GG CC
A T C G C
G T C G C
neutral
variation
advantageous
mutation
partial
selective
sweep
Human1
Human2
Human3
Human4
Human5
Human6
16
Selective sweep
AA TT CC GG CC
ancestor
AA TT CC GG CC
AA TT CC GG CC
GG TT CC AA CC
GG TT CC AA CC
AA TT AA GG CC
AA TT AA GG CC
GG TT CC AA CC
GG TT CC AA CC
AA TT CC GG CC
AA TT CC GG CC
GG TT CC AA CC
GG TT CC AA CC
AA TT CC GG TT
AA TT CC GG TT
GG TT CC AA CC
GG TT CC AA CC
GG TT CC GG CC
GG TT CC AA CC
GG TT CC AA CC
AA TT CC AA CC
GG TT CC GG CC
GG TT CC GG CC
AA TT CC GG CC
GG TT CC GG CC
neutral
variation
advantageous
mutation
partial
selective
sweep
G T C A C
G T C A C
G T C A C
G T C A C
G T C A C
G T C A C
G T C A C
G T C A C
G T C A C
G T C A C
G T C A C
G T C A C
A T C A C
G T C A C
G T C A C
G T C G C
A T C A C
A T C A C
recombination
Human1
Human2
Human3
Human4
Human5
Human6
recombination
16
Selective sweep
AA TT CC GG CC
ancestor
AA TT CC GG CC
AA TT CC GG CC
GG TT CC AA CC
GG TT CC AA CC
AA TT AA GG CC
AA TT AA GG CC
GG TT CC AA CC
GG TT CC AA CC
AA TT CC GG CC
AA TT CC GG CC
GG TT CC AA CC
GG TT CC AA CC
AA TT CC GG TT
AA TT CC GG TT
GG TT CC AA CC
GG TT CC AA CC
GG TT CC GG CC
GG TT CC AA CC
GG TT CC AA CC
AA TT CC AA CC
GG TT CC GG CC
GG TT CC GG CC
AA TT CC GG CC
GG TT CC GG CC
neutral
variation
advantageous
mutation
partial
selective
sweep
recombination
GGGTTTCCCAAACCC
GGGTTTCCCAAACCC G T CGGG
ATTT
CCCCAAACCC G T C A C
G T C A C
GGGTTTCCCAAACCC
GGGTTTCCCAAACCC G T CGGG
ATTT
CCCCAAACCC G T C A C
G T C A C
GGGTTTCCCAAACCC
GGGTTTCCCAAACCC G T CGGG
ATTT
CCCCAAACCC G T C A C
G T C A C
GGGTTTCCCAAACCC
GGGTTTCCCAAACCC G T CGGG
ATTT
CCCCAAACCC G T C A C
G T C A C
AAATTTCCCAAACCC
GGGTTTCCCAAACCC A T CGGG
ATTT
CCCCAAACCC G T C A C
G T C A C
GGGTTTCCCGGGCCC
AAATTTCCCAAACCC G T CAAA
GTTT
CCCCAAACCC A
G T C A C
A
G T C A C
recombination
selective G T
sweep ends
G T
C A C
G T C A C
G T C A C
C A C
G T C A C
G T C A C
Human1
Human2
Human3
Human4
Human5
Human6
G T C A C
G T C A C
G T C A C
frequent non-ancestral alleles
& many rare
ancestral
alleles
A T C A C
G T C A C
G T C A C
G T C G C
A T C A C
A T C A C
16
candidates for the selected sites are the two amino-acid substitutions specific to humans in exon 7.
Individuals with disruption of FOXP2 have multiple difficulties
with both expressive and receptive aspects of language and grammar, and the nature of the core deficit remains a matter of debate18–
20
. Nevertheless, a predominant feature of the phenotype of affected
individuals is an impairment of selection and sequencing of fine
orofacial movements18, an ability that is typical of humans and not
Recent positive selection of the 2 amino
acids:
present in
the great apes. We speculate that some human-specific
feature of FOXP2, perhaps one or both of the amino-acid substi1. frequent non-ancestral alleles near
exon
7 7, affect a person’s ability to control orofacial
tutions
in exon
movements and thus to develop proficient spoken language. If
2. many rare (ancestral) alleles - recent
selection.
this speculation
is true, then the time when such a FOXP2 variant
became fixed in the human population may be pertinent with
regard to the evolution of human language. We estimated this
time point using a likelihood approach. Under a model of a
randomly mating population of constant size, the most likely date
since the fixation of the beneficial allele is 0, with approximate 95%
confidence intervals of 0 and 120,000 years. Our point-estimate of 0
Positive selection
Coop et al.
- 5 Myr
- 70 Myr
0
2/0***
Human
0/2
0/7
0/5
0/2
C himp
0/2
G orilla
1/2
Orang-utan
0/5
Rhesus
1/131
Mouse
statisti
simula
recom
decrea
popula
the ch
human
ratio t
packag
human
(http:/
predic
specifi
positio
the pr
not be
Projec
estima
from t
gene (
located
Mode
A sum
since t
summ
selecti
polym
selecti
propo
(here,
spaced
of obt
are in
size of
is not c
assum
that on
estima
human
rate pe
param
polym
and
replacement
nucleotide substitutions mapped on a phylogeny of
FIG. 1.—The gene model for FOXP2, variation data for a modern human sample and genealogical cartoon. (a)Figure
A subset2ofSilent
the gene
model
(based
nsembl 48) for FOXP2 showing exons 4–8 (tan boxes) with spliced-out introns in between. The region surveyed
in Enard etBars
al. (2002)
is indicated
primates.
represent
nucleotide changes. Grey bars indicate amino-acid changes.
e red bar, below which are the polymorphic intronic sites (gray triangles) and the 2 human-specific amino acid substitutions in exon 7 (overlapping
le circle and green diamond). (b) Phased haplotypes from Enard et al. (2002), for the 9 sites with high-frequency–derived alleles in the extant
an sample. Open red circles denote the ancestral variant, and closed red circles denote the derived variant. Ancestral
haplotypes
areAUGUST
defined 2002 | www.nature.com/nature
© 2002 Nature Publishin
NATURE
| VOL(white)
418 | 22
ose carrying the ancestral allele at one or more of the sites with high-frequency–derived alleles. Blue circles indicate the fixed amino acid
estimated fixation of the mutation: < 200,000 years ago
17
when did it happen?
Krause et al. (2007)
Coop et al.(2008)
FOXP2 Human
mutation found in
neanderthal DNA
fixation
300,000
years ago?
gene flow
between
populations
(too many
ancestral alleles
in both
populations)
- 300,000 yrs
0
18
Selection for language?
There was a selection for the 2 amino acid replacements
what is the advantage?
physiological?
learning ability?
motor control?
deducing rules?
planning?
Did selection lead to a fundamental difference from other species?
19
?”‫ ּכִי הַּכֹל הָבֶל‬,‫הַּבְהֵמָה אָיִן‬-‫“ּומֹותַר הָאָָדם מִן‬
Terrace (1979)
S. Pinker, “The language instinct” (1995).
Nim eat Nim eat.
Drink eat me Nim.
Me gum me gum.
Tickle me Nim play.
Me banana you banana me you give.
Banana me me me eat.
Noam Chomsky
20
?”‫ ּכִי הַּכֹל הָבֶל‬,‫הַּבְהֵמָה אָיִן‬-‫“ּומֹותַר הָאָָדם מִן‬
Terrace (1979)
S. Pinker, “The language instinct” (1995).
Nim eat Nim eat.
Drink eat me Nim.
Me gum me gum.
Tickle me Nim play.
Me banana you banana me you give.
Banana me me me eat.
Nim Chimpsky
20
?”‫ ּכִי הַּכֹל הָבֶל‬,‫הַּבְהֵמָה אָיִן‬-‫“ּומֹותַר הָאָָדם מִן‬
Terrace (1979)
S. Pinker, “The language instinct” (1995).
Nim eat Nim eat.
Drink eat me Nim.
Me gum me gum.
Tickle me Nim play.
Me banana you banana me you give.
Banana me me me eat.
Nim Chimpsky
20
We argue that an understanding of the faculty of language requires substantial
interdisciplinary cooperation. We suggest how current developments in linguistics can
be profitably wedded to work in evolutionary biology, anthropology, psychology, and
neuroscience. We submit that a distinction should be made between the faculty of
language in the broad sense (FLB) and in the narrow sense (FLN). FLB includes a
sensory-motor system, a conceptual-intentional system, and the computational
mechanisms for recursion, providing the capacity to generate an infinite range of
expressions from a finite set of elements. We hypothesize that FLN only includes
recursion and is the only uniquely human component of the faculty of language. We
further argue that FLN may have evolved for reasons other than language, hence
comparative studies might look for evidence of such computations outside of the
domain of communication (for example, number, navigation, and social relations).
Grammar
• Chimpanzees learn vocabulary
• Parrots have categorical perception
• Parrots can express desires
• Frogs have names
• Ants have generalization abilities
• Chimpanzees transmit messages
• Song birds imitate
I
humans ac
In explo
lution, it is
questions c
nicative sy
computatio
those unde
low, many
have been l
between th
view (1), q
putational
those conc
targeted at
abstract co
and conce
view shou
claim again
f a martian graced our planet, it would be tures; it might further note that the human
struck by one remarkable similarity among faculty of language appears to be organized
Earth’s living creatures and a key difference. like the genetic code— hierarchical, generaConcerning similarity, it would note that all tive, recursive, and virtually limitless with
living things are designed on the basis of
highly conserved developmental systems
that read an (almost)
universal language encoded in DNA base
pairs. As such, life is
arranged hierarchically with a foundation
of discrete, unblendable units (codons, and,
for the most part,
genes) capable of combining to create increasingly complex and virtually limitless varieties
of both species and individual organisms. In
contrast, it would notice
the absence of a universal code of communication (Fig. 1).
If our martian nat- Fig. 1. The animal kingdom has been designed on the basis of highly conserved develop
universal language coded in DNA base pairs. This system is shown on the left in terms of a
uralist were meticu- lack a common universal code of communication, indicated on the right by unconnected ani
lous, it might note
that the faculty mediating human communication appears remarkrespect to its scope of expression. With these
tation and
• 2 year old kids have grammar!
21
Grammar
• Chimpanzees learn vocabulary
• Parrots have categorical perception
• Parrots can express desires
• Frogs have names
• Ants have generalization abilities
• Chimpanzees transmit messages
• Song birds imitate
• 2 year old kids have grammar!
Al-Sayyid Bedouin
sign language
21
Summary
• mutations in FOXP2 cause language impairments
• 2 amino acid replacements were recently selected
• what functions were selected?
• many species have high communication skills, not grammar
• what are the necessary ingredients for human language?
22