Supporting Information
Metabolic changes in schizophrenia and human brain evolution
Philipp Khaitovich, Helen E. Lockstone, Matthew T. Wayland, Tsz Mon Tsang,
Samantha D Jayatilaka, Arfu J. Guo, Jie Zhou, Mehmet Somel, Laura W Harris, Elaine
Holmes, Svante Pääbo and Sabine Bahn
I. Supplementary Figures
Figure S1. Principal component analysis of the metabolite abundance profiles
residuals in 33 individuals after sex and age linear regression analysis
Metabolite abundance residuals calculation for sex (A) and age (B) effects (Materials and
methods). The analysis is based on 21 detected metabolites. Each point represents an
individual. The colors indicate: blue – human controls, gray – human schizophrenia
patients, orange – chimpanzees, red – rhesus macaques.
Figure S2. Bootstrap analysis of the ratio of human/chimpanzee lineage length
The length of the lineages was estimated using neighbor-joining algorithm. Bootstrap
analysis was performed 500 times over metabolites (A) or over individuals within each
species (B). The bootstrap results are shown for the 9 metabolites with significant
concentration difference between human controls and schizophrenia patients (Group 1,
blue) and 12 metabolites with no difference between these two groups (Group 2, red).
The box area represents the range between the data first and the third quartiles. The
whiskers indicate the borders of the 95% confidence interval.
Figure S3. Extent of the linkage disequilibrium and the recombination rate for
genes associated with metabolites affected and not affected in schizophrenia
The main plot shows distribution of the linkage disequilibrium for 40 genes associated
with 9 metabolites affected in schizophrenia (G1) and 81 genes associated with 12
metabolites not affected in schizophrenia (G2) in three human populations: Africans
(red), Europeans (yellow), and Chinese (blue). The insert shows distribution of the
recombination rate measurements for the same genes. The thick line inside the box shows
median value, the box covers data distribution between the first and the third quartiles,
and the whiskers indicate 95% of the values distribution.
II. Supplementary Tables
Table S1. Sample Information
46
31
Fluphenazine
mg
equivalents
0
0
28
52
0
0
6.7
22
31
45
0
0
0
6.7
31
0
6.6
6.5
36
0
58
0
Sample ID
Group
Age
(years)
Sex
Brain pH
ctr_01
human controls
49
M
6.5
ctr_02
human controls
51
M
6.7
ctr_03
human controls
38
F
6.7
ctr_04
ctr_05
ctr_06
human controls
human controls
human controls
35
34
55
M
M
M
6.7
6.5
6.7
ctr_07
human controls
49
F
ctr_08
human controls
46
M
ctr_09
ctr_10
human controls
human controls
47
39
M
F
ctr_11
human controls
71
M
M
Post mortem
interval (hrs)
0
0
ctr_12
human controls
45
sch_01
human SZ patients
45
F
6.5
52
20000
sch_02
sch_03
human SZ patients
human SZ patients
51
53
M
F
6.6
6.5
43
130000
13
15000
sch_04
human SZ patients
37
M
6.8
30
20000
sch_05
human SZ patients
33
M
6.5
sch_06
human SZ patients
32
F
6.8
29
36
20000
10000
sch_07
sch_08
human SZ patients
human SZ patients
45
36
M
F
6.7
6.5
35
50
27
600
sch_09
human SZ patients
42
M
6.5
19
18000
sch_10
human SZ patients
52
M
6.5
16
60000
chz_01
chz_02
chimpanzees
chimpanzees
12
12
M
M
chz_03
chimpanzees
7
M
chz_04
chimpanzees
12
M
chz_05
chimpanzees
44
F
rhe_01
rhesus macaques
18
F
rhe_02
rhesus macaques
18
F
rhe_03
rhesus macaques
7
M
rhe_04
rhesus macaques
15
F
rhe_05
rhesus macaques
7
M
rhe_06
rhesus macaques
5
M
Table S2. Representation of schizophrenia-related expression changes in gene ontology (GO) categories positively selected during human evolution
Genes*
p-value GO:0008152
6321
0.0000
metabolism
GO:0006631
133
0.0256
fatty acid metabolism
GO:0019752
395
0.0001
carboxylic acid metabolism
GO:0006082
397
0.0001
organic acid metabolism
GO:0006118
287
0.1957
electron transport
GO:0006091
490
0.0163
generation of precursor metabolites and energy
GO:0015980
139
0.0082
energy derivation by oxidation of organic compounds
GO:0006221
21
0.2256
pyrimidine nucleotide biosynthesis
GO:0006259
561
0.8381
DNA metabolism
GO:0006399
79
0.0891
tRNA metabolism
GO:0006139
2841
0.0723
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
GO:0019219
1834
0.2002
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
GO:0006281
202
0.1788
DNA repair
GO:0006974
235
0.2197
response to DNA damage stimulus
GO:0009719
254
0.2803
response to endogenous stimulus
GO:0006350
1873
0.2920
transcription
GO:0006351
1763
0.2397
transcription, DNA-dependent
GO:0045449
1801
0.2348
regulation of transcription
GO:0045786
164
0.0925
negative regulation of progression through cell cycle
GO:0007283
131
0.9906
spermatogenesis
GO:0048232
131
0.9906
male gamete generation
GO:0007276
153
0.9726
gametogenesis
GO id
GO name
General classification
Metabolism
Nucleic acid metabolism
DNA repair
Transcription
Spermatogenesis
*Number of genes in a given GO category assayed by microarray.
p-value from Wilcoxon Rank Sum test for differential expression. Categories with p<0.03 are highlighted in bold type.
Summary of GO analysis (above) and estimation of false discovery rate
p-value cutoff
1
Number sig.
GO groups in
real data 2
avg. num. sig.
GO groups in
permuted
FDR 4
permutation p-value
data 3
0.001
3
0.0219
0.0073
0.0017
0.01
4
0.2158
0.0540
0.0106
0.02
5
0.4424
0.0885
0.0102
0.03
6
0.6667
0.1111
0.0083
0.05
6
1.115
0.1858
0.0257
0.1
9
2.1995
0.2444
0.0174
1
The Wilcoxon Rank Sum Test was used to test each GO category for differential expression; summary results for various p-value thresholds are shown
2
Number of significant GO categories at the given p-value threshold for real data
3
To estimate the false discovery rate (FDR), gene rankings were permuted 10000 times and the test repeated on each permuted dataset. The average
number of significant GO categories over the 10000 tests was computed
4
The FDR was calculated as the average number of significant GO categories in 10000 permuted datasets divided by the number of significant GO
categories observed in the real data
5
The permutation p-value is the proportion of 10000 tests on permuted data that yielded an equal or greater number of significant GO categories as
observed in the real data
At p<0.05, 6 GO categories showed evidence for differential expression in schizophrenia. All 6 remained significant at p<0.03 and thus this was reported
in the manuscript, with FDR estimated at 11%.
5
Table S3. GO groups showing excess of expression changes in both schizophrenia and human
evolution
GO id
GO:0008152
GO:0006631
GO:0019752
GO:0006082
GO:0006091
GO:0015980
Genes*
Up**
Down
pvalue†
adjusted
p-value‡
591
275
316
0.0998
0.1894
metabolism
11
4
0.1185
0.1894
fatty acid metabolism
25
26
1.0000
1.0000
27
26
1.0000
1.0000
16
27
0.1263
0.1894
4
12
0.0768
0.1894
15
51
53
43
16
metabolism
fatty and carboxylic acid
metabolism
electron transport and energy
pathways
GO name
carboxylic acid metabolism
organic acid metabolism
generation of precursor metabolites
and energy
energy derivation by oxidation of
organic compounds
*Number of differentially expressed genes in a given GO
category (t-test at an FDR of 25%).
** Up- and Down- regulation in schizophrenia patients
compared to controls.
†p-value from Binomial test for overrepresentation of upand down-regulated genes in a given GO category.
‡FDR adjusted p-value from Binomial test for
overrepresentation of up- and down-regulated genes in a
given GO category.
Table S4 could not be included in this document due to size and can be downloaded from
http://www.picb.ac.cn/Comparative/metabolites001/tableS3.zip
Table S5. Assignment of NMR spectra peaks to metabolites and
metabolite groups
Peak
number
Chemical
shift
Peak
position*
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
1.324
1.336
1.893
1.906
1.919
2.021
2.039
2.051
2.056
2.063
2.072
2.076
2.088
2.110
2.121
2.134
2.147
2.157
2.288
2.300
2.313
2.344
2.348
2.356
2.361
2.369
2.374
2.683
2.689
2.709
2.715
3.040
3.205
3.224
3.232
3.262
3.277
3.293
3.348
3.419
3.430
3.441
3.523
3.527
3.539
3.544
3.559
3.566
3.577
3.609
3.625
3.641
3.647
3.660
3.667
3.748
3.755
3.760
3.767
3.932
4.056
4.061
4.066
4.093
4.105
4.116
4.128
3297
3343
5574
5624
5675
6084
6157
6206
6226
6254
6289
6306
6354
6439
6484
6537
6588
6630
7153
7202
7251
7377
7394
7425
7445
7475
7498
8733
8757
8837
8862
10160
10819
10897
10929
11048
11110
11172
11394
11676
11721
11763
12091
12110
12158
12177
12237
12265
12309
12437
12501
12565
12590
12639
12669
12991
13022
13039
13070
13727
14226
14245
14265
14373
14419
14466
14511
* Data point corresponding to the peak mode after
the peak alignment procedure in the complete NMR
spectrum as listed in Supplementary T able 2.
Metabolite
Lactate
Lactate
Gamma-aminobutyric acid
Gamma-aminobutyric acid
Acetate
N-acetylaspartate
Glutamate/glutamine (2)
Glutamate/glutamine (2)
N-acetylaspartylglutamate
Glutamate (1)
Glutamate (1)
Glutamate (1)
Glutamate/glutamine (2)
Glutamate/glutamine (2)
Glutamine
Glutamine
Glutamine
Glutamine
Gamma-aminobutyric acid
Gamma-aminobutyric acid
Gamma-aminobutyric acid
Glutamate (2)
Glutamate/proline
Glutamate (2)
Glutamate (2)
Glutamate (2)
Glutamate (2)
N-acetyl-aspartate
N-acetyl-aspartate
N-acetyl-aspartate
N-acetyl-aspartate
Creatine
Choline
Phosphocholine
Glycerophosphocholine
Myo-inositol/taurine
Myo-inositol/taurine
Myo-inositol/taurine
Scyllo-inositol
T aurine
T aurine
T aurine
Myo-inositol
Myo-inositol
Myo-inositol
Myo-inositol
Glycine
Unknown
Unknown
Myo-inositol
Myo-inositol
Unknown
Unknown
Unknown
Unknown
Glutamate/glutamine (1)
Glutamate/glutamine (1)
Glutamate/glutamine (1)
Glutamate/glutamine (1)
Creatine
Myo-inositol
Myo-inositol
Myo-inositol
Lactate
Lactate
Lactate
Lactate
Table S6. Genes associated with fast-evolving and slow-evolving metabolite groups
Details of the 96 genes associated with the 9-metabolite fast evolving group
Ensembl Gene ID
HGNC Symbol
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
ENSG00000183044
ENSG00000151729
ENSG00000070669
ENSG00000176697
ENSG00000084774
ENSG00000129596
ENSG00000021826
ENSG00000183048
ENSG00000171793
ENSG00000204681
ENSG00000022355
ENSG00000151834
ENSG00000109158
ENSG00000145863
ENSG00000145864
ENSG00000163285
ENSG00000113327
ENSG00000182256
ENSG00000146276
ENSG00000111886
ENSG00000128683
ENSG00000136750
ENSG00000001084
ENSG00000023909
ENSG00000115419
ENSG00000135821
ENSG00000156052
ENSG00000152578
ENSG00000152208
ENSG00000171189
ENSG00000164418
ENSG00000163873
ENSG00000149403
ENSG00000176884
ENSG00000183454
ENSG00000150086
ENSG00000161509
ENSG00000124493
ENSG00000113262
ENSG00000137825
ENSG00000196586
ENSG00000148053
ENSG00000122884
ENSG00000185345
ENSG00000178921
ENSG00000128059
ENSG00000171862
ENSG00000059573
ENSG00000106688
ENSG00000110436
ENSG00000079215
ENSG00000105143
ENSG00000131389
ENSG00000011083
ENSG00000139874
ENSG00000109424
ENSG00000175567
ENSG00000175564
ENSG00000106789
ENSG00000112294
ENSG00000077800
ENSG00000115840
ENSG00000163655
ENSG00000137563
ENSG00000176749
ENSG00000072682
ENSG00000051128
ENSG00000103942
ENSG00000152413
ENSG00000153291
ENSG00000131459
ENSG00000004864
ENSG00000100372
ENSG00000128654
ENSG00000123159
ENSG00000131748
ENSG00000188338
ENSG00000135423
ENSG00000143811
ENSG00000085491
ENSG00000105655
ENSG00000146166
ENSG00000148082
ENSG00000114120
ENSG00000100253
ENSG00000161270
ENSG00000127080
ENSG00000104524
ENSG00000177542
ENSG00000197121
ENSG00000111371
ENSG00000139344
ENSG00000161653
ENSG00000123643
ENSG00000179520
ENSG00000174032
ABAT
SLC25A4
ASNS
BDNF
CAD
CDO1
CPS1
SLC25A10
CTPS
GABBR1
GABRA1
GABRA2
GABRA4
GABRA6
GABRB2
GABRG1
GABRG2
GABRG3
GABRR1
GABRR2
GAD1
GAD2
GCLC
GCLM
GLS
GLUL
GNAQ
GRIA4
GRID2
GRIK1
GRIK2
GRIK3
GRIK4
GRIN1
GRIN2A
GRIN2B
GRIN2C
GRM4
GRM6
ITPKA
MYO6
NTRK2
P4HA1
PARK2
PFAS
PPAT
PTENP1
ALDH18A1
SLC1A1
SLC1A2
SLC1A3
SLC1A6
SLC6A6
SLC6A7
SSTR1
UCP1
UCP2
UCP3
CORO2A
ALDH5A1
FKBP6
SLC25A12
GMPS
GGH
CDK5R1
P4HA2
HOMER3
HOMER2
HOMER1
SLC25A27
GFPT2
SLC25A13
SLC25A17
MTX2
GIPC1
STARD3
SLC38A3
GLS2
PYCR2
SLC25A24
GLULD1
SHC3
SLC25A36
MIOX
NPHS1
IPPK
PYCRL
SLC25A22
SLC38A1
AMDHD1
NAGS
SLC36A1
SLC17A8
SLC25A30
Details of the 48 genes associated with the 12-metabolite slow evolving group
Ensembl Gene ID
HGNC Symbol
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
ENSG00000087085
ENSG00000145020
ENSG00000130203
ENSG00000142192
ENSG00000136881
ENSG00000110721
ENSG00000205560
ENSG00000168539
ENSG00000181072
ENSG00000184984
ENSG00000101204
ENSG00000170175
ENSG00000147432
ENSG00000117971
ENSG00000108556
ENSG00000104879
ENSG00000181019
ENSG00000123453
ENSG00000130005
ENSG00000171766
ENSG00000109738
ENSG00000060558
ENSG00000114353
ENSG00000078369
ENSG00000161217
ENSG00000176974
ENSG00000182199
ENSG00000187714
ENSG00000107165
ENSG00000108039
ENSG00000206561
ENSG00000176749
ENSG00000133027
ENSG00000070214
ENSG00000100156
ENSG00000132837
ENSG00000090857
ENSG00000131069
ENSG00000111666
ENSG00000129749
ENSG00000129353
ENSG00000166275
ENSG00000115665
ENSG00000154930
ENSG00000164303
ENSG00000101438
ENSG00000181873
ENSG00000123643
ACHE
AMT
APOE
APP
BAAT
CHKA
CHKB
CHRM1
CHRM2
CHRM5
CHRNA4
CHRNB1
CHRNB3
CHRNB4
CHRNE
CKM
NQO1
SARDH
GAMT
GATM
GLRB
GNA15
GNAI2
GNB1
PCYT1A
SHMT1
SHMT2
SLC18A3
TYRP1
XPNPEP1
COLQ
CDK5R1
PEMT
SLC44A1
SLC16A8
DMGDH
ACSS2
CHPT1
CHRNA10
SLC44A2
AS3MT
SLC5A7
ACSS1
ENPP6
SLC32A1
C1orf69
SLC36A1
Table S7. mRNA expression of genes associated with metabolites significantly altered
in schizophrenia
Ensembl Gene ID
ENSG00000115665
ENSG00000114353
ENSG00000206561
ENSG00000188985
ENSG00000161217
ENSG00000109738
ENSG00000164303
ENSG00000132837
ENSG00000087085
ENSG00000147432
ENSG00000107165
ENSG00000070214
ENSG00000178445
ENSG00000136881
ENSG00000123453
ENSG00000166275
ENSG00000166275
ENSG00000166275
ENSG00000166275
ENSG00000168539
ENSG00000110721
ENSG00000182199
ENSG00000111666
ENSG00000081760
ENSG00000184984
ENSG00000171766
ENSG00000117971
ENSG00000090857
ENSG00000181019
ENSG00000170175
ENSG00000108556
ENSG00000133027
ENSG00000176974
ENSG00000129353
ENSG00000130203
ENSG00000130005
ENSG00000104879
ENSG00000131069
ENSG00000101438
ENSG00000154930
ENSG00000101204
ENSG00000142192
ENSG00000205560
ENSG00000122121
ENSG00000102230
HGNC
Symbol
SLC5A7
GNAI2
COLQ
DHFR
PCYT1A
GLRB
ENPP6
DMGDH
ACHE
CHRNB3
TYRP1
SLC44A1
GLDC
BAAT
SARDH
C10orf32
AS3MT
C10orf32
AS3MT
CHRM1
CHKA
SHMT2
CHPT1
AACS
CHRM5
GATM
CHRNB4
NQO1
CHRNB1
CHRNE
PEMT
SHMT1
SLC44A2
APOE
GAMT
CKM
ACSS2
SLC32A1
ACSS1
CHRNA4
APP
CHKB
XPNPEP2
PCYT1B
Chimpanzee
Human
C1
C2
C3
C4
C5
H1
H2
H3
H4
H5
2.03
2.18
2.01
1.52
2.17
2.56
2.09
1.96
2.41
1.91
1.57
2.89
2.20
2.15
1.71
1.09
1.09
1.96
1.96
2.36
2.34
2.32
2.40
2.42
0.68
2.55
1.98
1.97
2.30
2.01
1.70
2.11
2.32
2.66
2.58
1.90
2.12
2.31
2.08
2.40
1.99
3.20
2.10
1.64
2.29
2.09
2.29
2.15
2.07
2.27
2.55
2.24
1.88
2.27
1.97
1.92
2.85
2.18
2.06
1.71
1.65
1.65
1.92
1.92
2.34
2.23
2.55
2.42
2.29
2.01
2.56
2.22
2.09
2.40
2.08
1.95
2.24
2.31
2.74
2.70
1.93
2.00
2.30
2.19
2.49
1.86
3.21
2.03
1.78
2.31
1.94
2.21
2.25
2.16
2.14
2.37
1.99
1.14
2.13
1.57
0.98
2.83
2.39
2.15
1.62
1.13
1.13
1.69
1.69
2.42
2.32
2.30
2.32
2.37
1.37
2.52
1.91
2.14
2.07
1.87
1.77
2.04
2.21
2.68
2.50
1.94
1.33
2.27
2.04
2.31
1.88
3.20
2.10
1.82
2.29
1.77
2.22
2.23
2.13
2.29
2.37
2.08
1.85
2.26
1.90
1.90
2.85
2.26
2.09
1.64
1.10
1.10
1.83
1.83
2.46
2.31
2.34
2.28
2.46
1.43
2.57
1.90
2.15
2.34
1.86
1.71
2.14
2.33
2.73
2.64
1.97
2.07
2.34
2.13
2.45
1.99
3.21
2.11
1.73
2.35
2.12
2.00
2.20
1.80
2.16
2.59
1.67
0.76
2.01
2.00
1.87
2.67
2.11
1.97
1.57
1.62
1.62
2.01
2.01
2.44
2.31
2.27
2.45
2.34
1.82
2.47
2.04
2.06
2.05
1.84
1.79
1.96
2.23
2.62
2.49
1.60
1.95
2.19
2.19
2.36
1.80
3.18
2.08
1.65
2.04
2.12
2.31
2.12
2.12
2.37
2.49
2.07
1.90
2.22
2.03
2.01
2.63
2.14
1.02
1.56
2.09
2.09
2.32
2.32
2.48
2.28
2.21
2.33
2.36
1.44
2.49
2.05
2.20
2.05
1.86
1.81
2.14
2.08
2.50
2.23
2.02
1.84
2.17
1.93
2.34
1.72
3.25
2.14
1.67
2.30
1.91
2.39
2.19
2.45
2.39
2.23
2.19
1.29
2.22
1.96
1.66
3.09
2.17
0.79
1.48
2.21
2.21
2.16
2.16
2.28
2.41
2.15
2.41
2.21
2.36
2.85
1.45
2.46
2.13
2.00
1.80
2.06
2.32
2.78
2.41
2.10
2.02
2.47
1.67
2.67
1.76
3.25
2.27
1.48
2.42
1.96
2.37
2.18
2.22
2.34
2.43
1.99
1.99
2.28
2.07
1.86
2.79
2.33
1.62
1.59
2.08
2.08
2.01
2.01
2.26
2.33
2.26
2.41
2.32
1.67
2.62
2.18
2.34
2.57
2.06
1.84
2.10
2.22
2.74
2.30
1.91
1.89
2.35
1.87
2.45
1.80
3.24
2.09
1.60
2.45
1.94
2.30
2.10
2.02
2.36
2.39
2.05
2.07
2.19
1.76
2.01
2.87
2.24
1.35
1.24
1.98
1.98
2.10
2.10
2.39
2.36
2.23
2.42
2.34
2.16
2.71
2.12
2.21
2.21
1.92
1.60
2.07
1.92
2.67
2.30
1.94
1.81
2.30
1.73
2.56
1.81
3.26
2.16
1.70
2.33
2.14
2.27
2.21
2.36
2.32
2.40
1.91
2.03
2.12
1.90
2.23
2.72
2.19
1.26
1.62
2.17
2.17
1.99
1.99
2.34
2.37
2.19
2.51
2.37
0.74
2.63
2.07
2.23
2.10
1.83
1.95
2.17
2.01
2.67
2.35
1.87
1.85
2.27
1.99
2.61
1.82
3.27
2.11
1.63
2.32
Table S8. mRNA expression of genes associated with metabolites not altered in schizophrenia
Ensembl Gene ID
ENSG00000171793
ENSG00000159423
ENSG00000163873
ENSG00000023909
ENSG00000085491
ENSG00000143811
ENSG00000143811
ENSG00000084774
ENSG00000128683
ENSG00000128654
ENSG00000115419
ENSG00000021826
ENSG00000198380
ENSG00000115840
ENSG00000197121
ENSG00000131389
ENSG00000188338
ENSG00000144746
ENSG00000114120
ENSG00000163655
ENSG00000152208
ENSG00000151729
ENSG00000163285
ENSG00000151834
ENSG00000109158
ENSG00000128059
ENSG00000079215
ENSG00000011083
ENSG00000145863
ENSG00000022355
ENSG00000113327
ENSG00000152413
ENSG00000129596
ENSG00000072682
ENSG00000145864
ENSG00000113262
ENSG00000131459
ENSG00000112294
ENSG00000196586
ENSG00000164418
ENSG00000124493
ENSG00000001084
ENSG00000146166
ENSG00000146276
ENSG00000111886
ENSG00000185345
ENSG00000077800
ENSG00000004864
ENSG00000070669
ENSG00000137563
ENSG00000104524
ENSG00000106688
ENSG00000148053
ENSG00000156052
ENSG00000148082
ENSG00000127080
ENSG00000106789
ENSG00000136750
ENSG00000151151
ENSG00000122884
ENSG00000148672
ENSG00000148672
ENSG00000059573
ENSG00000152578
ENSG00000149403
ENSG00000177542
ENSG00000176697
ENSG00000110436
ENSG00000175567
ENSG00000175564
HGNC
Symbol
CTPS
ALDH4A1
GRIK3
GCLM
SLC25A24
PYCR2
PYCR2
CAD
GAD1
MTX2
GLS
CPS1
GFPT1
SLC25A12
SLC6A6
SLC38A3
ARL6IP5
SLC25A36
GMPS
GRID2
SLC25A4
GABRG1
GABRA2
GABRA4
PPAT
SLC1A3
SLC6A7
GABRA6
GABRA1
GABRG2
HOMER1
CDO1
P4HA2
GABRB2
GRM6
GFPT2
ALDH5A1
MYO6
GRIK2
GRM4
GCLC
GLULD1
GABRR1
GABRR2
PARK2
FKBP6
SLC25A13
ASNS
GGH
PYCRL
SLC1A1
NTRK2
GNAQ
SHC3
IPPK
CORO2A
GAD2
IPMK
P4HA1
GLUDP5
GLUD1
ALDH18A1
GRIA4
GRIK4
SLC25A22
BDNF
SLC1A2
UCP2
UCP3
C1
2.34
1.58
2.41
1.37
1.62
2.09
1.69
2.11
2.73
2.40
2.95
1.73
2.56
2.66
2.61
2.11
2.23
2.83
2.58
2.73
2.20
2.79
2.48
2.72
2.77
2.32
2.99
2.15
1.79
2.93
3.00
2.85
2.31
2.09
2.83
1.90
2.15
2.51
2.38
2.44
2.08
2.42
1.91
1.85
1.12
2.37
2.04
2.41
3.01
2.11
2.01
2.66
2.97
3.02
2.57
2.10
2.23
2.59
1.78
2.29
3.06
3.06
2.20
2.48
2.19
2.43
1.99
3.17
2.05
2.01
Chimpanzee
C2
C3
C4
2.26
2.31
2.28
1.85
1.96
1.75
2.39
2.36
2.37
1.54
1.67
1.73
1.85
1.60
1.84
2.16
2.05
2.10
1.65
1.45
1.72
2.09
2.14
2.19
2.71
2.65
2.61
2.24
2.31
2.32
2.95
2.92
2.90
1.73
1.64
1.72
2.59
2.49
2.49
2.66
2.58
2.60
2.58
2.53
2.42
2.31
2.32
2.35
2.25
2.22
2.43
2.88
2.79
2.77
2.53
2.50
2.55
2.74
2.63
2.69
2.17
2.06
2.09
2.83
2.74
2.71
2.61
2.30
2.46
2.72
2.73
2.66
2.75
2.72
2.65
2.17
2.20
2.15
3.14
2.88
3.01
2.18
2.28
2.06
1.98
1.68
1.79
2.93
2.87
2.90
3.02
2.99
2.95
2.78
2.74
2.72
2.25
2.16
2.07
2.13
1.98
2.04
2.78
2.76
2.76
1.96
2.00
1.95
2.19
2.18
2.19
2.60
2.46
2.57
2.21
2.32
2.35
2.39
2.43
2.40
2.22
2.13
2.00
2.43
2.34
2.44
1.92
1.81
1.85
1.96
1.65
1.60
1.41
1.46
1.47
2.22
2.36
2.28
2.22
1.93
1.92
2.35
2.32
2.39
2.95
2.93
2.95
2.00
1.99
2.02
2.02
2.03
1.92
2.70
2.57
2.60
2.99
2.95
2.95
3.06
3.03
3.00
2.60
2.63
2.55
2.17
2.12
2.14
2.06
2.19
2.16
2.56
2.60
2.51
1.81
1.84
1.91
2.52
2.16
2.21
3.08
3.06
3.06
3.08
3.06
3.06
2.30
2.17
2.21
2.45
2.50
2.41
2.19
2.25
2.24
2.46
2.50
2.48
1.90
2.03
1.86
3.21
3.15
3.18
2.03
1.95
2.18
1.93
1.94
1.65
C5
2.21
1.62
2.37
1.42
1.76
1.95
1.52
2.10
2.78
2.41
2.97
1.63
2.53
2.70
2.51
2.41
2.19
2.82
2.67
2.75
2.11
2.87
2.62
2.83
2.78
2.42
3.04
1.95
1.71
2.92
3.03
2.92
2.15
2.04
2.90
1.82
2.31
2.45
2.36
2.42
2.12
2.37
1.82
1.80
1.46
2.21
1.90
2.15
2.98
2.16
1.89
2.66
2.97
3.00
2.46
2.04
2.13
2.61
1.79
2.09
3.09
3.09
2.20
2.52
1.94
2.39
1.78
3.24
1.82
1.89
H1
2.22
1.77
2.15
1.85
1.86
2.01
1.46
1.95
2.71
2.46
3.03
1.86
2.58
2.67
2.66
2.29
2.12
2.93
2.53
2.73
2.39
2.80
2.20
2.76
2.85
2.21
2.71
2.35
1.33
3.02
3.06
2.84
2.57
2.09
2.87
1.91
2.31
2.60
2.23
2.56
2.10
2.29
1.60
1.75
1.63
2.54
2.01
2.05
3.05
1.98
1.97
2.71
2.95
3.03
2.72
2.11
1.89
2.64
1.68
1.99
3.01
3.01
2.25
2.66
2.14
2.44
1.83
2.96
1.87
1.95
H2
2.17
1.50
2.34
1.64
1.87
2.08
1.62
2.04
2.45
2.38
2.94
2.23
2.50
2.62
2.47
2.43
2.30
2.88
2.47
2.68
2.21
2.67
2.52
2.71
2.61
2.16
3.08
2.07
1.63
2.89
2.95
2.67
2.39
2.10
2.70
1.71
2.26
2.53
2.62
2.37
1.87
2.53
1.62
1.66
1.66
2.39
2.15
2.45
2.93
1.90
1.82
2.47
3.00
2.99
2.61
2.16
1.98
2.31
1.68
2.28
3.13
3.13
2.17
2.43
2.18
2.31
1.87
3.20
2.05
1.86
Human
H3
2.21
2.04
2.28
1.90
1.83
1.93
1.67
1.94
2.68
2.37
3.05
2.11
2.54
2.67
2.49
2.07
2.04
2.92
2.47
2.71
2.22
2.74
2.67
2.76
2.75
2.11
3.05
2.19
1.77
2.94
3.07
2.70
2.51
2.16
2.82
1.94
2.15
2.56
2.36
2.49
2.10
2.36
1.81
0.79
1.70
2.40
2.07
2.08
2.97
1.95
1.80
2.72
3.01
3.07
2.70
2.12
2.10
2.44
1.60
2.21
3.12
3.12
2.32
2.48
2.14
2.44
1.62
3.22
1.95
1.76
H4
2.16
1.93
2.34
1.64
1.87
2.01
1.51
2.02
2.72
2.40
3.03
1.95
2.53
2.70
2.61
2.20
2.31
2.90
2.54
2.69
2.16
2.78
2.71
2.86
2.79
2.21
3.06
2.23
1.80
3.02
3.06
2.73
2.49
2.10
2.86
1.86
2.16
2.58
2.42
2.53
2.00
2.39
1.69
0.93
1.71
2.46
2.20
2.28
3.02
2.00
1.96
2.65
3.01
3.06
2.67
2.09
2.03
2.57
1.64
2.32
3.14
3.14
2.27
2.52
2.13
2.43
1.78
3.22
1.94
1.89
H5
2.15
1.83
2.36
1.44
1.78
2.01
1.79
1.88
2.73
2.41
3.04
1.90
2.55
2.69
2.63
2.15
2.23
2.92
2.51
2.70
2.22
2.77
2.65
2.83
2.78
2.15
3.04
2.28
1.88
2.98
3.06
2.76
2.47
2.22
2.83
2.05
2.24
2.60
2.29
2.49
2.17
2.35
1.83
1.24
1.66
2.45
2.16
2.08
3.04
1.92
2.00
2.68
3.03
3.05
2.69
2.12
2.05
2.57
1.71
2.34
3.18
3.18
2.29
2.51
2.09
2.52
1.90
3.24
1.75
1.76
ENSG00000168959
ENSG00000139344
ENSG00000179520
ENSG00000150086
ENSG00000111371
ENSG00000135423
ENSG00000139874
ENSG00000165555
ENSG00000080824
ENSG00000186297
ENSG00000182256
ENSG00000137825
ENSG00000103942
ENSG00000183454
ENSG00000178921
ENSG00000131748
ENSG00000161653
ENSG00000183048
ENSG00000161509
ENSG00000185624
ENSG00000123159
ENSG00000105143
ENSG00000151151
ENSG00000105655
ENSG00000051128
ENSG00000161270
ENSG00000161270
ENSG00000171189
ENSG00000100033
ENSG00000100372
ENSG00000182890
ENSG00000125675
ENSG00000102078
ENSG00000047230
ENSG00000102050
ENSG00000102287
ENSG00000176884
GRM5
AMDHD1
SLC17A8
GRIN2B
SLC38A1
GLS2
SSTR1
C14orf148
HSP90AA1
GABRA5
GABRG3
ITPKA
HOMER2
GRIN2A
PFAS
STARD3
NAGS
SLC25A10
GRIN2C
P4HB
GIPC1
SLC1A6
IPMK
HOMER3
NPHS1
PRODH2
GRIK1
PRODH
SLC25A17
GLUD2
GRIA3
SLC25A14
CTPS2
PRAF2
GABRE
GRIN1
2.77
1.84
2.03
2.68
2.92
2.22
1.94
1.71
3.27
2.64
2.45
2.06
2.20
2.75
2.13
2.29
1.84
2.29
2.00
2.27
2.39
2.34
1.69
1.92
2.28
1.53
1.53
2.18
2.03
1.96
2.60
2.89
2.09
2.36
2.20
1.97
2.58
2.85
1.95
1.98
2.66
2.83
2.12
1.92
2.20
3.28
2.71
2.42
2.06
2.24
2.73
2.26
2.28
1.95
2.14
2.15
2.44
2.40
2.20
1.88
1.89
2.17
1.69
1.69
2.12
1.77
1.84
2.65
2.88
2.07
2.49
2.18
1.76
2.65
2.74
1.89
1.79
2.76
2.91
2.18
2.20
1.78
3.20
2.65
2.37
2.04
2.26
2.77
2.16
2.22
1.92
2.35
2.19
2.17
2.45
2.28
1.56
2.09
2.17
1.55
1.55
2.08
1.93
1.82
2.56
2.87
1.96
2.45
2.20
1.19
2.58
2.78
1.69
2.15
2.67
2.89
2.10
1.76
1.00
3.23
2.66
2.43
1.97
2.24
2.72
2.27
2.30
1.85
2.47
2.13
2.30
2.48
2.15
1.80
1.90
2.34
1.67
1.67
2.16
1.98
1.89
2.46
2.86
1.84
2.46
2.23
1.65
2.57
2.84
1.84
1.62
2.72
2.94
2.25
1.90
1.38
3.22
2.39
2.43
2.09
2.37
2.84
2.17
2.00
1.90
1.85
2.01
2.23
2.34
2.22
1.87
1.79
2.15
1.41
1.41
2.31
2.01
1.88
2.52
2.88
2.01
2.42
2.06
1.67
2.50
2.87
1.40
1.63
2.78
2.93
2.28
2.28
1.00
3.22
2.68
2.32
2.34
2.30
2.77
2.16
2.16
1.81
1.87
1.78
2.47
2.36
2.15
1.91
2.24
1.83
1.56
1.56
2.31
1.60
1.92
2.59
2.92
2.08
2.39
2.23
1.57
2.67
2.65
1.85
1.61
2.59
2.91
2.10
2.14
0.99
3.22
2.60
2.37
1.98
2.24
2.67
2.10
2.25
1.71
1.98
2.30
2.46
2.36
1.94
2.00
1.85
2.22
1.38
1.38
2.04
2.11
1.79
2.57
2.79
1.94
2.47
2.21
1.67
2.62
2.83
1.48
1.90
2.67
2.91
2.31
2.17
1.02
3.23
2.62
2.41
2.05
2.27
2.73
2.20
2.27
1.83
1.85
1.98
2.57
2.37
2.03
2.07
1.97
1.79
1.64
1.64
2.19
1.98
1.77
2.59
2.88
2.05
2.37
2.21
1.31
2.57
2.82
1.77
1.71
2.72
2.96
2.28
2.18
1.43
3.23
2.78
2.46
2.06
2.21
2.72
2.10
2.17
1.82
1.91
2.10
2.56
2.36
2.18
1.75
1.97
1.98
1.57
1.57
2.34
1.87
1.85
2.63
2.89
2.18
2.32
2.12
0.97
2.64
2.85
0.71
2.11
2.74
2.96
2.29
2.14
1.92
3.22
2.76
2.53
2.01
2.11
2.74
2.09
2.06
1.86
1.80
1.99
2.50
2.37
2.14
1.82
1.98
1.74
1.75
1.75
2.28
1.93
1.73
2.62
2.93
2.09
2.31
2.19
1.50
2.71