Transcript MtDNA divesity in Central Africa: from hunter

MtDNA diversity in Central Africa:
from hunter-gathering to
agriculturalism
CNRS-Institut Pasteur, Paris
Lluis Quintana-Murci
Blandine Massonnet
Francesca Luca
Hélène Quach
DDL, Lyon
Lolke van der Veen
Jean-Marie Hombert
Lucas Sica
Giselle X
Patrick Mouguiama
MNHN, Paris
Evelyne Heyer
Alain Froment
Serge Bahuchet
Questions
• Is the linguistic grouping of populations
supported by real genetic relationships?
• Get genetic insights into the Bantu-speaking
populations from Gabon
• The putative Semitic origin of Fang populations
• Clarify the origins of some mtDNA lineages
• Shed light on the ways of migration of Bantu
speaking populations from their homeland
towards the east, southeast and southwest
Questions…during the course of this project
• Extending our area of study towards the north:
Cameroon
• Include Pygmy populations in our study
• Understand to which extent the transition from
hunter-gathering to agricultural lifestyle has
influenced the genetic diversity of these
populations
• Evaluate the genetic exchange between
agriculturalists and hunter-gatherers
• Get insights into the gene pool of Pygmy
populations: unique origin? Different origins?
Common initial gene pool with agriculturalists?
Central/West African collection:
-1258 samples from Gabon and Cameroon
- 257 Pygmy samples
- 1001 Bantu-speaking agriculturalists
- Average sample size 55 (30-90)
- 20 Bantu-speaking agriculturalists pops:
-GABON: Benga, Duma, Eviya, Fang, Galoa,
Eshira, Kele, Kota, Makina, Ndumu, Nzebi,
Obamba, Orungu, Punu, Shake, Teke, Tsogo
-CAMEROON: Ewondo, Fang, Ngumba
- 5 Pygmy populations:
2 Baka populations from Central/East Cameroon
1 Baka population from Gabon
1 Bakola population from Cameroon
1 Tikar/Medzan population from Cameroon
D-LOOP
OH
12S rRNA
Cyt b
mtDNA
16S rRNA
ND5
ND6
ND1
- Maternally inherited
Mitochondrial DNA
16.5 kb
ND2
ND4
OL
ND4L
ND3
COX I
COX II
A8 A6
COX III
- No recombination
- High mutation rate
 Coding-region SNPs markers:
Advantages:
-Define main lineage clusters in the mtDNA phylogeny
-Reliable comparison of frequency clusters among populations
-Mostly stable mutations
Disadvantages :
-Bias in the definition of haplogroups? Partial information?
HVS-I sequence diversity:
Advantages:
-No bias since all information is taken into consideration
-High mutation rate -> useful in microevolutionary studies
-Provide with useful information about demographic past
Disadvantages:
-High mutation rate -> homoplasy -> under-estimation of
population genetic distances
Combined approach using both sets of markers
Salas et al. 2002
Schematic representation of African mtDNA phylogeny
- Some lineages are defined on
the basis of only HVS-I
sequence data
- Some HVS-I motifs are
composed of highly-evolving
mutations
- Misleading phylogenetic
classification of some lineages
due to recurrent mutations
Salas et al. AJHG (2002)
COMPLETE MTDNA SEQUENCE LITERATURE -> L1
Root
Root
1048
3516A
4312
5442
6185
9042
9347
9755
10589
10664
11914
12007
13276
3666
7055
7389
13789
14178
14560
L0
L1
597
1438
4586
9818
3756
3981
4025
4044
4086
4225
4232
5153
6815
7154
8113A
8152
8251
8270
8281-9bpD
8392
8545
11854
12121
12172
12234
12810
14221
15466
15766
15930
15941
850
1243
2836A
4541
4907
5811
6938
9755*
7257
8911
8994
9136
10499
10876
10920
10939
11296
11299
11653
12070
13020
13590
13819
13928C
14020
14182
14371
14374
L0d
2245
5231
5603
8428
8566
11176
11641
12720
14308
15136
15431
2352
2768
3308
5036
5046
5393
5655
6827
7867
8248
12519
14203
14769
15115
10321
13485
5147
5711
6257
8281-9bpD
8460
11172
L0a1
6917
7055*
7498
7789
9370
9377
9966
11302
11396
11719
12019
12501
12616
13293
15905
15978
2060
7347
8292
5911
14007
8185
15924
9545
9554
11143
13116
14755
19
1539A
5628
7258
8191
4454A
8087
14088
15301
5563
11812
14106
15099
2308
5984
10398
11167
11257
12930T
14034
7146
16
15
43
7
31
6150
6253
7076
7337
8784
8877
10792
10793
11654
12049
13149
L1c1
3866
2245C
L0a2
3372
5237
11269
12172
13281
3796T
3843
11899
14148
5096
6752
7660
7693
9272
2885
5300
9355
23
93
3843*
4454A*
5826C
2
14
4688
5108
5460
7948
10804
11914
13965
15470
15626
15942D
2755
2863
3513
3927
4506
7202
9647
10398
12768
7571
18
709
1738
5951
6071
8027
9072
10586
12810
14000A
14911
L1c
6182
8928
9311
15663
30
1438
2395D
L0a
L0k
2650
7673
8251
825A
2758
2885
7146
8468
8655
10688
10810
13506
15301
37
3
13
4454A*
4634
7692
8419
9336
10365
12477
14766
66
9
1291
4824
5553
8237
8271.1T
8276.1C
8279
8279.1C
8287
8619
9824
9861
10084
11611
12681
14338
14393
14460
15025
15160
62
L1b
1406
1438
13293
14812
710
3693
6548
6989
13880A
3396
8790
13194
11017
14460
1766
6378
14053
13781
13980
9098
L1c2
1420
2157.1A
3777
5901.1C
15016
15784
3777*
7744
8251
13212
13281
14812
5237
9052
11914
12172
15758
10
78
633
723
3421
5580
7985G
10031
10071
11164
13941G
14682G
15672
56
25
26
79
92
33
60
69
76
8
47
84
L2/L3
2416
8206
9221
10115
13105
13590
769
1018
3594
4104
7256
7521
13650
L2
L2
719
954
1211
3316
3537
4562
5069T
6014
6221
8383
9377
9971
11935
12189
13356
13638
13708
14299
15592
15697
15734
15889
11944
2789
7175
7274
7771
11914
13803
14566
2332
870
2159
3254A
3434
3693
6231
8856
9554
9941
10700
10955
11353
14845
15263
15458
15703
15777C
L2a
709
3010
4104
6752
7664
8721
9932
10790
11767
12507
13068
13827
14118
15939
12693
15784
1442
7624A
12236
15110
15217
680
709
3200A
13958C
15849
L2c
13928C
3918
5285
15244
15629
6152
15391
6875A
7278
10454
15211
15421
5581
13708
13805G
14974G
3336
3438
5048
4216
5460
8227
8480
12684
3495A
8790
12630
7521
731
3705
11204
14434
14927
14131
44
36
50
46
5
42
63
65
80
82
29
74
73
15229
8541
14599
4655
7978G
67
1282
13810
6164
10920
5237
9758
10604
55
14311
90
930
3010
3308
3338
3936A
6311
6663
7702
8119
8604
14173
14566*
15451
87
86
5366A
14180
2083
4371
9986
14034
14239
1706
2358
4158
4370
4767
5027
5331A
5814
6713
8080
8387
12948
14059
5255
8733
11909
14118
3221
4596
14374
5201
5988
6437
12026
14061A
15236
L2b
4185
5744
8925
14544
15326
15945.1T
8987
9903
13708
4
6026
13924
4841
8856
10828
1007C
3777
7985G
8080*
13629
28
57
5237
15562
61
53
88
91
49
12
35
22
83
72
L3
13105
L3
3450
5773
6221
9449
10086
10373
13914A
15311
15824
15942D
5147
7424
8618
13886
14284
L3d
1719
4688
7389
13752
15061
L3b
11002
10373*
15311*
15942D*
3492
4164
8393
9305
10424T
15314
15942D*
6366
11347
11800
15883
5063
8875
11176
2332
9533
11401
7618
8616
11800
15099
11800C
921
3010
4679
6150
13326
15110
8530
1977
12705
6680
1503
4048
4203
5471
7648
10640
10915
11887
13611
4040
7765
8709
9151
14128
2903
3203
5372
9111
9254
9728
9932
11239
12870
13542
15496
1900
4910
5046
6272
41
81
1719
4388
4688
4742
5004
5300
5492
7058A
7858
7861
8781A
8943
9509
9575
10197
11377
11590
12175
12236
12519
12999
14587
14862
15646
2352
10819
14212
10400
8701
9540
10398
10873
L3e
6221
6587
14152
15670
15942
14905
8650
4733
709
12396
L3h
1719
3204
10370
14571A
3438
10042
4395
8281-9bpD
1927
15113
15358
4392
11914
2483
5580
9377
11017
11722
12850
14580
15932
5201
6267
750
6932
7978G
7985G
13269
4655
4688
4823
5102
12414
14869
14974G
2702
3915
5584
9490
11257
13749
M*
2000
6524
9554
10667
10816
13101C
4655
13197
13651
15812
10286
12397
5262
12248
6261
10816*
1
75
N*
750
1438
2706
4769
7028
8860
11719
12705
13105
14766
15301
15326
H2a
34
24
38
39
77
45
59
52
27
89
20
32
17
68
48
71
85
6
70
11
21
40
54
64
51
58
Our analyses
• Sequence of HVS-I region
• 25 coding-region SNP analyses taking into
consideration previous phylogenies AND
complete mtDNA sequence data
phylogenies
Population diversity and structure
HZ
PYGMIES
BANTUS
1
0,9
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
TSO
TEK
SHA
PUN
ORU
OBA
NZE
NDU
NGU
MAK
KEL
KOT
GIS
GALOA
FANG-G
FANG-C
EWOND O
EVI
BEN
DUM
BAKO
BAKA-G
BAKA-CAM2
TIKAR
BAKA-CAM1
0
Analysis of MOlecular VAriance
Entire sample
Among populations
Within populations
Pygmies versus Bantu
8%
92%
Among groups
Among population within groups
Within populations
16.3%
1.3%
82.3%
Genetic diversity and neutrality tests
- The 5 groups of Pygmies show signals of constant-size populations
- All Bantu agriculturalists show signals of population expansion, with the
exception of the Benga, the Eviya and the Ewondo
POPULATION RELATIONSHIPS
EXACT TEST OF SAMPLE DIFFERENTIATION
SIGNIFICANT FST
Principal components analyses
1,5
MAK
1,0
NZE
BEN FAN-C
DUM
NGU
PC2 23%
OBA
KOT
,5
EWD
0,0
GIS
KEL
NDU
TEK
FAN-G
PUN
-,5
SHA
TSO
-1,0
GAL
Northern cluster
-1,5
EVI
-2,0
-3
-2
-1
0
PC1 50%
1
2
Pygmy populations: Diversity and population distances
5
4
Khoisan
3
WA
2
PC2 16%
Pygmies
SEA
1
West/East/SE
SA
Pi
0
NA
-1
Central Africa
EA
-2
CA_S
North Africa
-3
-3
CA
-2
-1
0
PC1 28%
1
2
MtDNA haplogroup diversity and phylogeography in Central Africa
Estimated frequencies in Central African populations
BAKA
BAKA
BAKOLA
Hg
Cameroun
Gabon
Cameroon
L0a
10
0
0
90
0
0
0
0
0
0
0
0
0
0
0
0
0
0
97,4
0
0
0
0
0
0
0
2,6
0
0
0
0
0
0
100
0
0
0
0
0
0
0
0
0
0
0
L1*
L1b
L1c
L2*
L2a
L2b
L2c
L2d
L3*
L3b
L3d
L3e
L3f
L3g
BEN
DUM
EVI
EWD
FANG
Cameroon Cameroon
10
0
10
44
0
4
0
2
0
0
2
4
20
4
0
12,8
0
8,5
36,2
0
12,8
2,1
0
2,1
0
0
8,5
12,8
4,2
0
14,3
0
3,6
25
0
25
14,2
7,1
0
0
3,6
3,6
3,6
0
0
16
0
12
44
0
12
0
0
0
0
16
0
0
0
0
0
0
6,2
31,3
0
15,6
0
0
0
0
18,7
6,3
6,2
12,5
3,2
FANG
GAL
GIS
KEL
KOT
MAK
NDU
Gabon
7,2
0
11,4
25,7
0
14,3
0
0
1,4
0
5,7
2,8
24,3
4,3
2,9
NGU
NZE
OBA
ORU
PUN
SHA
T EK
T SO
4,8
0
7,9
39,7
0
4,8
3,2
1,6
0
0
1,6
6,3
22,2
6,3
1,6
6,3
0
4,2
33,3
2,2
16,7
0
0
2,2
2,2
2,2
2,2
20,2
8,3
0
14,3
0
0
42,9
0
23,8
0
0
0
0
0
4,8
9,5
4,7
0
3,8
0
0
28,8
1,9
15,5
1,9
0
3,8
5,8
9,6
1,9
23,1
3,9
0
9,6
0
3,8
44,2
0
17,4
1,9
1,9
0
0
0
3,8
13,6
1,9
1,9
12,8
0
10,9
27,3
0
12,7
0
3,6
0
0
0
3,6
25,5
3,6
0
4,7
0
0
39,1
0
26,5
3,1
0
1,6
0
0
4,7
18,7
1,6
0
Cameroon
7,9
0
0
29,5
0
19,6
0
9,8
1,9
0
1,9
13,8
7,8
5,9
1,9
13,8
0
9,8
43,2
0
7,9
1,9
3,9
3,9
5,9
0
1,9
3,9
3,9
0
8,4
0
4,3
39,7
0
14,7
0
2,2
0
0
0
2,2
20,2
8,3
0
12,6
0
3,7
35,7
0
5,3
5,3
0
3,5
1,8
1,8
5,3
7,1
17,9
0
6,7
2,2
13,4
46,7
0
8,9
0
0
0
2,2
4,4
0
11,1
2,2
2,2
12,8
0
7,7
28,2
2,5
20,6
0
2,6
2,6
0
5,1
0
17,9
0
0
14,7
1,3
8
26,7
0
13,3
0
0
0
2,7
1,3
0
14,7
14,7
2,6
- Haplogroups L1c, L2a and L3e are the most represented in Central
African populations
- L1c is the most widespread lineage in all groups of Pygmies here
studied (90-100%)
-L1c is also the main lineage characterising Bantu-speaking
agriculturalists from Gabon and Cameroon (25-50%)
Frequency distribution of L1c and sublineages in Central Africa
1
0,9
L1c*
0,8
0,7
0,9
0,8
0,6
0,7
0,6
0,5
0,5
L1c*
0,4
0,4
L1c*
L1c1
0,3
0,3
L1c1a
L1c1a1
0,2
0,1
L1c2
0,10
L1c3
Total L1c
NG
!K
U
NO
0
TIKAR
R
BAKA_CAM2 TH
BAKA-Cam1
BAKA-G
W
BAKOES
BIAKA T
CE
MBUTI
NT
MBEZELE
BEN R A
L
DUM
EVI
M
FANGABON B
UT
GAL
I
GIS
KEL B
KOT IAK
A
MAK
NDU
NZE
EA
ST
OBA
SO
ORU U
TH
PUN
EA
SHA
ST
TEK
TSO
0,2
L1c*
L1c phylogeny based on complete mtDNA sequences of Pygmy and Bantus
Root
3666
7055
7389
13789
14178
14560
825A
2758
2885
7146
8468
8655
10688
10810
13506
15301
L1
1438
2395D
5951
6071
8027
9072
10586
12810
13485
14000A
14911
769
1018
3594
4104
7256
7521
13650
8701
9540
10398
10873
L1c
10321
593
930
2251
2315
4562
5074
5231
5460
5465
8829
9611
10398
13659
13933
14470
14798
15700
3796T
3843
11899
14148
4454A
8087
14088
4491
5913
10667
13194
2308
5984
11167
12930T
9096T/C
11150
14016
9098
5300
7785
6182
8928
9311
15663
2885
9355
8420
P15
P17
P17
P09
P03
P10
P21
P09
P03
P10
P21
Pygmy
L1c1
Bantu
L1c1a
Literature
L1c1a1
P02
P18
P20
P23
P04
P11
P08
P02
P18
P20
P23
P04
P08
P11
37
P05
P07
6752
7660
7693
9272
3843*
4454A*
5826
2
14
3
P16
P06
P24
P14
P05
P07
P16
P06
P24
P14
4167
8657
4688
10804
13965
15470
15942D
4634
7692
9336
12477
7571
4454A*
8419
10365
14766
13
66
8988
12735
13834
P01
P22
P12
P01
P22
P12
9
L1c3
7498
7789
9370
9377
9966
11396
11719
12019
12501
12616
13293
13485*
L1c2
5108
5460
7948
11914
15626
2755
2863
3513
3927
4506
7202
9647
10398
12768
11257
1413
3394
7258
P15
10398
15301
14034
2141
5277
8769
9580
12164
13174
14040
15777
L0
6150
6253
7076
7337
8784
8877
10792
10793
11654
12049
13149
L1c1
1291
4824
5553
8619
9861
10084
12681
14393
15025
1420
2157.1A
3777
5901.1C
15016
15784
8237
8271.1T
8276.1C
8279
8279.1C
8287
9824
11611
14338
14460
15160
3792
4688
8277
12957
15301*
15784
15806
3777*
7744
8251
13212
13281
14812
5237
9052
11914
12172
15758
62
P25
10
78
P25
750
1438
2706
4769
7028
8860
11719
12705
13105
14766
15301
15326
6917
7055*
10398
11302
15905
15978
633
723
3421
5580
7985G
10031
10071
11164
13941G
14682G
15672
56
25
2283
6221A
15226
745,1
3027
3525
3600
4853
11852
11984
12507
14669
629
3210
3434
4755
8251
8417
10042T
11317
12400
12542
13708
13981
14794
16017
P19
P13
P19
P13
L1b
L2
L3
N*
H2a
Conclusions I
•
The linguistic northern cluster (Mitsogo, Galoa,
Eviya) is supported by mtDNA data
•
The linguistic southern cluster seems less
supported by genetic analyses, suggesting a more
heterogeneous group of populations
•
Need for fine linguistic-genetic correlations studies
Conclusions II
• Apart of populations from the northern cluster, the
Shake appears to be the most differentiated
populations
• The Fang population does not present an detectable
trace of their Semitic origin -> Y-chromosome?
• Our data suggest a Central African origin for L1c ->
highest frequencies and diversity in Central Africa as
compared to receivals areas such as the southwest
and southeast
Conclusions III: Pygmies
• All Pygmy populations exhibit reduced diversity at both the
haplogroup and sequence levels
• Bantus and Pygmies share a common gene pool exemplified by the
sharing of L1c lineage
• Admixture between Pygmies and Bantus seems to have occurred in
a single direction, since no other lineages than L1c have penetrated
the Pygmy gene pool
• In Western Pygmies, this lineage has reached almost fixation
probably due to small population sizes and strong genetic drift
• Need for further molecular characterization of L1c lineages since
current phylogeny leads to misleading classification of some
lineages
Perspectives
• Extending our analyses to the autosomes
• Sequence-based genome-wide analyses in order to
better infer demographic past of both agriculturalist and
hunter-gatherer populations in central Africa
• Infer the origin of Pygmy populations and evaluate
genetic exchange with agriculturalist neighbors
• Differential adaptation processes depending on lifestyle > cultural behavior and infectious diseases