AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 118:146 –153 (2002)

Extreme mtDNA Homogeneity in Continental Asian
Populations
Hiroki Oota,1,2* Takashi Kitano,3 Feng Jin,4 Isao Yuasa,5 Li Wang,4 Shintaroh Ueda,2 Naruya Saitou,3and Mark Stoneking1
1

Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany
Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan
3
National Institute of Genetics, Mishima 411-8540, Japan
4
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
5
School of Medicine, Tottori University, Yonago 683-8503, Japan
2

KEY WORDS

mtDNA; Asian population; patrilocality; genetic homogeneity

ABSTRACT
Mitochondrial DNA (mtDNA) variationin continental Asia has not been well-studied. Here, wereport mtDNA HV1 sequences for 84 Xi’an and 82 Changsha Han Chinese, 89 Honshu Japanese, and 35 Vietnamese. Comparison of these sequences with other Asian
mtDNA sequences reveals high variability within populations, but extremely low differentiation among Asian populations. Correlations between genetic distance and geo-

graphic distance, based on mtDNA and Y chromosome
variation, indicate a higher migration rate in females thanin males. This may reflect patrilocality, as suggested previously, but another plausible hypothesis is that the demographic expansion associated with the spread of agriculture in Asia may be responsible for the extreme genetic
homogeneity in Asia. Am J Phys Anthropol 118:146 –153,
2002. © 2002 Wiley-Liss, Inc.

The Asian continent encompasses the easternpart of Eurasian continent and is the source fromwhich emanated the circum-Pacific peoples, such as
Native Americans and the Oceanians. Molecular anthropologists and geneticists have studied mtDNA
variation of populations from the Americas (Ward etal., 1991; Shields et al., 1993; Torroni et al., 1993a,b;
Kolman et al., 1995) and Oceania (Redd et al., 1995;
Redd and Stoneking, 1999; Sykes et al., 1995) tounderstand their biological history. The prehistoricmigrations from the Asian continent to the Japanesearchipelago (Horai et al., 1996) and to aboriginal
Taiwan (Melton et al., 1998) have also been studied
by analyzing mtDNA variation. However, regarding
the present peoples of the source area, the Asian
continental region, very little is known about
mtDNA variation. To date, sequences of the first
hypervariable region (HV1) have been obtained only
for a few populations (Kolman et al., 1996; Horai etal., 1996; Lee et al., 1997; Comas et al., 1998), withsome additional data in the form of restriction fragment length polymorphisms (Ballinger et al., 1992;
Ding et al., 2000). Asian HV1 sequences overall account for only 10% of the more than 6,000 human
mtDNA sequences currently deposited in databases
such as DDBJ/EMBL/GenBank and HvrBase (Handt
et al., 1998; Burckhardt et al., 1999). Additional continental Asian sequence data are therefore necessary
to characterize Asian populations in comparison with
European, African, and circum-Pacific populations.
Moreover, recently Y-chromosome haplotype data
based on single nucleotide polymorphism (SNP)
have been reported for continental Asian popula-tions (Chu et al., 1998; Perez-Lezaun et al., 1999; Suet al., 1999). Additional mtDNA data would thus
enable a comparison of migration rates between
males and females in continental Asia, as previous
studies have done in other areas (Seielstad et al.,
1998; Perez-Lezaun et al., 1999). Here we report
mtDNA nucleotide sequences from four Asian populations, including two Han Chinese (Xi’an andChangsha), Honshu Japanese, and Vietnamese, andanalyze Asian mtDNA variability in a comparative
framework using 2,629 sequences from 54 worldwide populations. To investigate migration patterns
in males and females, we also compare mtDNA variation with published Y-chromosome variation andanalyze the relationship between genetic distanceand geographic distance for these two loci.

© 2002 WILEY-LISS, INC.

MATERIALS AND METHODS
Sampling and DNA extraction
Figure 1 shows the locations of the population samples in this study. The Han Chinese blood samples
Grant sponsor: Japanese Society for the Promotion oif Science;
Grant sponsor: Max Planck Society.
*Correspondence to: Hiroki Oota, Department of Genetics, Yale
University School of Medicine, 333 Cedar St., P.O. Box 208005, New
Haven, CT 06510-8005. E-mail: hiroki.oota@yale.edu
Received 16 October 2000; accepted 19 November 2001.
DOI 10.1002/ajpa.10056
Published online in Wiley InterScience (www.interscience.wiley.
com).

147

mtDNA HOMOGENEITY IN ASIA

Data analysis
Published data on HV1 sequences from additional
54 additional human populations from around theworld (Table 1) were included. Estimates of genetic
diversity and genetic distances were computed using
the program ARLEQUIN version 2.000, http://lgb.
unige.ch/arlequin, developed by S. Schneider, D. Roessli,
and L. Excoffier. A neighbor-joining (NJ) tree (Saitou andNei, 1987) was constructed using SENDBS, http://
www.cib.nig.ac.jp/dda/ntakezak.html#sendbs, developed by N. Takezaki. Bootstrap probabilities werecomputed with 1,000 replicates, using Da distances(Nei at al., 1983) and the model by Tamura and Nei(1993) of substitution, with ␣ ⫽ 0.26 (Meyer et al.,1999). Multidimensional scaling (MDS) analysis was
carried out with STATISTICA (StateSoft Software,Ltd.), using Fst values calculated under the model by
Tamura and Nei (1993).
RESULTS AND DISCUSSION

Fig. 1. Map of sampling locations for populations analyzed inthis study.

came from two cities, Xi’an and Changsha, located on
the Yellow and Yangtse Rivers, respectively. The Japanese blood samples were collected in Tottori Prefecture, Honshu, while the Vietnamese DNA samples
were obtained from first-generation South Vietnamese
immigrants to California. Genomic DNA was extracted by the QIAamp Blood Kit (QIAGEN).
Amplification and direct sequencing
PCR amplification of the HV1 region was performed using primers L15996 and H16401 (Vigilant
et al., 1989). Since the Vietnamese samples did notamplify with these primers, presumably because of
DNA degradation, additional primers H16218 and
L16209 (Stone and Stoneking, 1998) were used toamplify these samples. PCR was carried out as follows: initial denaturation at 92°C for 90 sec, followed by 40 cycles of denaturation at 92°C for 30 sec,
annealing at 57°C for 30 sec, and extension at 72°C
for 30 sec, followed by a final extension of 5 min at
72°C. PCR products were sequenced directly withthe same primers on an ABI PRISM 377 (PerkinElmer) by means of the Dye Terminator Cycle Sequencing kit (Perkin-Elmer). A total of 374 nucleotides (positions 16026 –16399; Anderson et al., 1981)of the HV1 region were obtained from the four Asian
populations. The nucleotide sequences have been submitted to DDBJ, http://www.ddbj.nig.ac.jp/Welcome-e.
htm [accession numbers AB047980-AB048181 (Xi’an,
Changsha, and Vietnamese), and AB048424-AB048512(Tottori)], and will also become available in HvrBase,
http://db.eva.mpg.de/hvrbase/ (Handt et al., 1998;
Burckhardt et al., 1999).

Overall, Asian populations exhibited high levels of
within-population mtDNA variation (Table 1).
Among all populations in Eurasia, the Vietnamese
had the highest number of mean pairwise differences (MPD) (9.10 ⫾ 4.29), and the Changsha population had the second highest number (7.91 ⫾
3.72), suggesting that in general, continental Asians
exhibit higher levels of mtDNA variation in thesouth than in the north. The decreasing cline in
mtDNA genetic diversity from the south to the northin Asia agrees with studies on classical genetic
markers (Saitou et al., 1994), microsatellites (Chu etal., 1998), and Y-chromosomal biallelic markers (Suet al., 1999). The average MPD for Asians washigher in the continental region (7.12) than the noncontinental region (6.57), and was 1.5 times higher
than that of 12 European populations from the continental region (4.63), and nearly equal to that of 15
sub-Saharan African populations (7.99) (Table 2).
In spite of the high variability within populations,
phylogenetic analyses demonstrate that genetic distances between Asian populations are very small.
The NJ tree (Fig. 2) for 35 worldwide populations
exhibits three major branches; including additional
populations from Table 1 does not change the structure of this tree (data not shown). The majority ofthe populations enclosed by the ellipse come fromeast/central Asia, with all branches in the ellipse
supported with less than 10% bootstrap probabilities, suggesting that the branching pattern in theellipse has little statistical support. Figure 3 showsa multidimensional scaling (MDS) plot with the same
populations as the NJ tree of Figure 2, except forthree African populations. Six populations (Basques,
British, Finns, Anatolia Turks, Turks, and Ainu),
who were in the central ellipse in Figure 2, are now
separate from the center. However, the Asian populations remain closely grouped spatially in the MDS
plot. Thus the Asian populations are quite closely
related to one another.

TABLE 1. Geographical classification of populations and diversity statistics1
Name of population

Size

MPD

Tajima’s D

Reference

84
82
18
370
103
17
16

7.40 ⴞ 3.49
7.91 ⴞ 3.72
7.44 ⫾ 3.65
6.52 ⫾ 3.09
7.68 ⫾ 3.61
5.99 ⫾ 3.00
5.79 ⫾ 2.92

ⴚ1.78*
ⴚ1.90*⫺1.53⫺2.19*⫺1.83*⫺1.35⫺1.11

Present study
Present study
Betty et al., 1996
Horai et al., 1996; Lee et al., 1997
Kolman et al., 1996
Shields et al., 1993
Torroni et al., 1993b

55
48
47
55

7.33 ⫾ 3.48
7.26 ⫾ 3.46
6.58 ⫾ 3.16
6.49 ⫾ 3.12

⫺1.85*⫺1.72*⫺1.92*⫺1.97*

Comas et al., 1998
Comas et al., 1998
Comas et al., 1998
Comas et al., 1998

35

9.10 ⴞ 4.29

ⴚ1.89*

Present study

89
51
52
28

5.94 ⴞ 2.86
7.03 ⫾ 3.35
7.62 ⫾ 3.61
7.31 ⫾ 3.52

ⴚ2.05*⫺1.28⫺1.61*⫺0.95

Present study
Horai et al., 1996
Horai et al., 1996
Melton et al., 1998

25
26
84

5.54 ⫾ 2.76
4.60 ⫾ 2.33
7.96 ⫾ 3.74

⫺1.76*⫺0.33⫺1.32

Sykes et al., 1995
Sykes et al., 1995
Vigilant et al., 1991; Redd et al., 1995;
Redd and Stoneking, 1999

Indian127

7.07 ⫾ 3.34

⫺1.47*

Mountain et al., 1995

Turks
Anatolia Turks

29
45

7.33 ⫾ 3.53
6.06 ⫾ 2.94

⫺1.97*⫺2.04*

Calafell et al., 1996
Comas et al., 1996

106
30
24
28
50
107
49
30
54
76
82
25

3.29 ⫾ 1.70
5.25 ⫾ 2.61
6.17 ⫾ 3.01
4.96 ⫾ 2.49
4.23 ⫾ 2.13
5.58 ⫾ 2.70
5.70 ⫾ 2.78
5.08 ⫾ 2.53
4.02 ⫾ 2.04
3.98 ⫾ 2.01
3.67 ⫾ 1.88
3.62 ⫾ 1.90

⫺2.23*⫺1.93*⫺0.93⫺1.73*⫺1.82*⫺1.87*⫺2.06*⫺1.85*⫺1.98*⫺1.78*⫺0.56⫺0.99

Bertranpetit et al., 1995
Calafell et al., 1996
Richards et al., 1996
Sajantila et al., 1995
Sajantila et al., 1995
Richards et al., 1996
Francalacci et al., 1996
Corte-Real et al., 1996
Corte-Real et al., 1996
Pult et al., 1994
Sajantila et al., 1995
Sajantila et al., 1995

100
39
69

5.04 ⫾ 2.46
5.72 ⫾ 2.80
4.74 ⫾ 2.35

⫺1.92*⫺1.17⫺2.03*

Piercy et al., 1993
Sajantila et al., 1995
Di Rienzo et al., 1991

!Kung
Biaka Pygmy
Mubti Pygmy
Mandenka
Egyptians
Fulbe
Hadza
Hausa
HereroKanuriKikuyuNubians
Southern Sudanese
Turkana
Yoruban

25
17
20
119
69
61
17
20
27
14
25
67
79
37
13

3.59 ⫾ 1.89
9.84 ⫾ 4.74
8.47 ⫾ 4.09
8.32 ⫾ 3.88
8.41 ⫾ 3.94
8.27 ⫾ 3.89
4.32 ⫾ 2.25
6.74 ⫾ 3.31
2.37 ⫾ 1.33
8.52 ⫾ 4.19
9.97 ⫾ 4.72
9.86 ⫾ 4.57
10.08 ⫾ 4.65
12.57 ⫾ 5.80
8.54 ⫾ 4.22

⫺1.04
1.22
2.16
⫺1.04
⫺1.61*
⫺0.86
2.23
⫺1.03
⫺1.34
⫺1.16
⫺1.10
⫺1.42
⫺1.40
⫺0.93
⫺0.17

Vigilant et al., 1991
Vigilant et al., 1991
Vigilant et al., 1991
Graven et al., 1995
Krings et al., 1999
Watson et al., 1996
Vigilant et al., 1991
Watson et al., 1996
Vigilant et al., 1991
Watson et al., 1996
Watson et al., 1996
Krings et al., 1999
Krings et al., 1999
Watson et al., 1996
Vigilant et al., 1991

Amerind (Brazil)
NgoebeArgentina

29
46
18

4.45 ⫾ 2.26
5.07 ⫾ 2.51
5.29 ⫾ 2.68

⫺0.20
1.68
⫺0.07

Ward et al., 1991
Kolman et al., 1995
Ginther et al., 1993; Torroni et al., 1993aAustralians
PNG
Vanuata

53
38
41

7.62 ⫾ 3.61
9.406 ⫾ 4.42
6.98 ⫾ 3.35

⫺1.80*⫺0.86⫺1.05

Redd and Stoneking, 1999
Vigilant et al., 1991; Redd et al., 1995
Sykes et al., 1995

Eurasia
Asia
Continental
East Asia
Xi’an Han Chinese
Changsha Han Chinese
Cantonese
KoreanMongolian
Siberian Altai
Russian Siberians
Central Asia
KazakhLowland Kirghiz
Highland Kirghiz
Uighurs
Southeast Asia
Vietnamese
Noncontinental
East Asia
Honshu Japanese
Ainu
Taiwan Han Chinese
Taiwanese
Southeast Asia
Philippines
Borneo Indonesia
East Indonesia
India
Middle East
EuropeContinental
Basques
Bulgaria
DanishEstonia
Finns
Germany
Italy (Tuscany)
North Spain
Portugal
Switzerland
Saami (Norway)
Saami (Sweden)
Noncontinental
BritishIcelanders
SardinianAfricaAmericas

Oceania1
Mean pairwise differences (MPD) were calculated using the distance method of Tamura and Nei (1993) (␣ ⫽ 0.26). Populations inboldface are data from this study.
* P ⬍ 0.05.

mtDNA HOMOGENEITY IN ASIA
TABLE 2. Genetic diversity within/between continental
populations

AfricaEuropeAsia
Eurasia

No. ofpopulations

Withinpopulations
average MPD

Betweenpopulations
average Fst

15
12
12
27

7.99 ⫾ 2.72
4.63 ⫾ 0.94
7.12 ⫾ 0.91
5.95 ⫾ 1.51

0.201
0.066
0.033
0.086

The homogeneity of Asian populations is also evidenced by Fst analyses. The average pairwise Fst
value for 12 continental Asian populations (0.033)
was 2, 3, and 6 times lower than that for 12 populations from continental European populations(0.066), 27 populations from the Eurasian continent(0.086), and 15 populations from Africa (0.201), respectively (Table 2). Inclusion of additional populations does not alter these conclusions (data notshown). Table 3 shows the average Fst values for
Asian populations in various combinations. The average Fst value of 0.005 was extremely low for thefour Han Chinese populations (Xi’an, Changsh, Cantonese, and Taiwan Han), similar to the average Fstof 0.006 for the four central Asian populations(Kazakh, Lowland Kirghiz, Highland Kirghiz, andUighurs). The average Fst was slightly increased to
0.019 for other East Asian populations (Korean,
Mongolian, Siberia Altai, and Honshu Japanese). Fst
values for other combinations of Chinese and Asian
populations ranged from 0.010 – 0.016 (Table 3). The
average Fst for all 15 populations from East andCentral Asia was 0.038, which is not significantly
different from that of 12 continental Asian populations, confirming that homogeneity extends from
East to Central Asia. However, the average Fst value
for four Southeast Asian populations (0.099) was
about three times higher than that for 12 populations from East and Central Asia.
The average Fst in Southeast Asian populations
was also high in the insular region. The average Fstof three insular Southeast Asian groups (0.121) was
about 1.5 times higher than that of 27 populations(see Table 1) from the whole Eurasian continent. For
2 of 3 insular Southeast Asian populations (Borneo
and Indonesian), Tajima’s D value (1989) was not
significantly different from 0 (Table 1), indicating no
signal of demographic expansions (Aris-Brosou andExcoffier, 1996). Tajima’s statistic was also not significantly different from 0 (Table 1) for five East
Asian populations (Cantonese, Siberian Altai, Russian Siberians, Ainu, and Taiwanese). Eliminatingthese five populations results in an average Fst
value of 0.015 for the remaining 10 East and Central
Asian populations, which is about half of the Fst
value obtained when these five populations are included (Table 3). Thus, overall, low levels of between-population differentiation are observed in
Asian populations, especially in the continental region. This conclusion agrees with a recent, smaller-149

scale study of mtDNA restriction site polymorphisms in Asian populations (Ding et al., 2000).
What might account for this extreme mtDNA homogeneity in Asia? There is more than one possible
explanation. For example, all of the Asian populations are food-producing groups, so one possibility isthat a low level of mtDNA differentiation between
populations might be a general phenomenon among
food-producing populations that share aspects of demographic history. In support of this observation,
elimination of two food-gathering populations (Saamis from Norway and Sweden) from the European
sample also results in an extremely low Fst value(0.014). Archaeological evidence suggests that in
East Asia, agriculture (mainly based on domesticrice) probably developed first on the Yangtse Riverby at least 5,000 years ago, and was spread by expanding populations of rice-cultivators (Harris,
1996). The presumed area where agriculture firstdeveloped corresponds quite closely to the geographic region inhabited by Changsha Han Chinese
and Vietnamese, who have extremely high levels of
within-population mtDNA variation. This trend,
higher within-population variation in the south
than in the north, is consistent with a recent analysis of mtDNA, Y chromosome, autosomal shorttandem repeat loci (Ding et al., 2000), and JC virus
variation in East Asian populations (Ding et al.,
2000; Guo et al., 2001), that suggests a lack of significant genetic boundaries between northern andsouthern populations (Ding et al., 2000; Guo et al.,2001). Thus, an Asian demographic expansion associated with the spread of large-scale agriculture may
be responsible for the low levels of between-population differentiation. Alternatively, a recent analysisof Y-chromosome variation points to an importantrole of Central Asia as a source of Eurasian genetic
diversity (Wells et al., 2001). Perhaps recent migrations from Central Asia explain the homogeneity ofeastern Asian populations. Further analyses of Ychromosome polymorphisms in eastern Asian populations, and of mtDNA and other loci in Central
Asian populations, are required to evaluate this hypothesis.
The geographic distribution of mtDNA was generated exclusively by female migration, and male andfemale migrations patterns may differ. To compare
female migration patterns with male migration patterns in Asia, we examined the correlation between
genetic distance (Fst) and geographic distance (km),based on the mtDNA sequences and the haplotype
frequency data of Y-chromosome biallelic markers(Su et al., 1999) (Fig. 4). The populations in theseanalyses are not identical, but they do come from thesame geographic regions in East and Southeast
Asia, including both the continental and the insularregions. For mtDNA, there was a significant correlation between Fst and geographic distance (r ⫽0.633, P ⬍ 0.01). Moreover, the slope of the best-fit
line for the Asian population data (2.0 ⫻ 10⫺5) was
not significantly different from that for European

150

H. OOTA ET AL.

Fig. 2. Population tree, showing mtDNA homogeneity in Asia. Population tree was constructed by the NJ method (Saitou and Nei,
1987), with 1,000 bootstrap replications. Scale bar below tree indicates genetic distance (Da), and numbers on branches indicate
bootstrap values (when greater than 10%). Ai, Ainu; Al, Altai of Siberia; An, Anatolia Turks; Au, Aboriginal Australian; Ba, Basques;
Bo, Borneo; Br, British; Ca, Cantonese; Fi, Finns; In, Indian; Ka, Kazakh; KiH, Kirghiz Highlander; KiL, Kirghiz Lowlander;
Ko, Korean; Mo, Mongolian; Ph, Philippines; PNG, Papua New Guinean; Tu, Turks; Tw, Taiwan Han Chinese; Ui, Uighurs.
Arrow represents root of the tree, using Mandenka, !Kung, and Pygmies as an outgroup. Populations in boldface are data from thisstudy.

populations (1.3 ⫻ 10⫺5; Seielstad et al., 1998). On
the other hand, the Fst values based on Y-SNP haplotypes were not significantly correlated with geographic distance (r ⫽ ⫺0.051, P ⬎ 0.05). The average
Fst value among Asian populations for the Y-chromosome (0.096) was about two times higher thanthat for mtDNA (0.056).

These results indicate that the rate of migration
for females, but not males, is related to geographic
distance. Moreover, the higher average Fst value for
the Y-chromosome, compared to mtDNA, indicatesthat males have not been moving as much as females. Thus, the lack of a correlation with geographic distance for the Y-chromosome could indi-mtDNA HOMOGENEITY IN ASIA

151

Fig. 3. MDS plot based on Fst values for 32 populations (omitting the three African populations from the NJ tree). Names ofoutlying and intermediate populations are shown, while unlabelled solid circles are Asian populations.
TABLE 3. Average Fst values in various combinations1
Various population combinations

Average Fst

4 Chinese (Xian, Changsha, Cantonese, andTaiwan Han)
4 Central Asians (Kazakh, Lowland Kirghiz,Highland Kirghiz, and Uighurs)
4 East Asians (Korean, Mongolian, Altai, andJapanese)
4 Chinese ⫹ 4 Central Asians
4 Chinese ⫹ 4 East Asians
4 Chinese ⫹ 4 Central Asians ⫹ 4 East Asians
15 East and Central Asians (4 Chinese ⫹ 4
Central Asians ⫹ 4 East Asians ⫹ Russian
Siberians, Ainu, and Taiwanese)
10 East and Central Asians (eliminating 5
populations whose Tajima D was not
significantly different from 0)
4 Southeast Asians (Vietnamese, Philipines,
Borneo, and Indonesians)

0.005
0.006
0.019
0.010
0.016
0.015
0.038
0.015
0.099

1
Pairwise Fst values were calculated under the distance methodof Tamura and Nei (1993), with ␣ ⫽ 0.26.

cate that the rate of male migration is so low thatgenetic drift is overcoming the influence of isolation
by distance. This pattern of higher female mobility
in Asian populations agrees with previous resultsfrom European and central Asian populations (Seielstad et al., 1998; Perez-Lezaun et al., 1999). Seielstad et al. (1998) attributed higher female mobility
to the widespread practice of patrilocality, in which
the female moves to the residence of the male after
marriage. This explanation recently received strong
support from a comparison of mtDNA and Y-chromosome variation in patrilocal and matrilocalgroups in northern Thailand (Oota et al., 2001),
which revealed the usual pattern observed in patri-Fig. 4. Correlation between genetic distance (Fst), based on(A) mtDNA and (B) Y-SNP haplotypes, and geographic distance(km) for East and Southeast Asian populations (12 and 19 populations for mtDNA and Y-chromosome, respectively). Dashed line
represents regression line for mtDNA (slope, 2.0 ⫻ 10⫺5, r ⫽ 0.633,
P ⬍ 0.01), and for Y-SNP haplotypes (r ⫽ ⫺0.051, P ⬎ 0.05).

local groups, of bigger differences between groups
based on assessment of the Y chromosome thanbased on mtDNA, but exactly the opposite pattern(bigger differences between groups based on mtDNA
than on the Y chromosome) for matrilocal groups.
In conclusion, we suggest that the extreme
mtDNA homogeneity observed in Asian populations
may reflect a recent demographic expansion arisingfrom successful subsistence due to rice agriculture.
The reduced homogeneity for the Y-chromosome
than for mtDNA in these cultivators could reflect the
influence of patrilocality operating within this demographic expansion. In this respect, we note thatrelative to other populations elsewhere, the average Fst value for the Y-chromosome among Asian
populations was 0.096, which is about half of the Fst
value for European populations (Fst ⫽ 0.215, as calculated from the data of Semino et al., 2000). Asian
populations also appear more homogeneous for the
Y-chromosome. However, it would be desirable tohave data on mtDNA, the Y chromosome, and autosomal loci from the same populations, to rule out any
sampling artifacts. Analyses of food-gathering populations should provide further insights into the152

H. OOTA ET AL.

reason(s) for the apparent genetic homogeneity of
Asian food-producing populations.
ACKNOWLEDGMENTS
The Han Chinese blood samples were collected by
F.J. and N.S. for the Japanese-Chinese Joint Research Project, “Study on Genetic and Cultural Diversity of Han Chinese,” and for Scientific Researchon the Priority Areas, “The Origin of the Japaneseand Japanese Culture,” which were supported by
the Ministry of Education, Science, Sport, and Culture, Japan, as a Grant-in-Aid for International Science Research given to N.S. The Japanese blood
samples were collected by I.Y. for the project, “TheOrigin of the Japanese and Japanese Culture,” as a
Grant-in-Aid given to I.Y. The Vietnamese samples
were donated by B. Budowle. We thank all the DNA
donors in China, Japan, and the US. We also thankF. Calafel for kindly sending Central Asian sequences, H. Kobayakawa for helpful technical assistance, and R. Cordaux, H. Kaessmann, M. Kayser, S.
Kumar, S. Meyer, I. Nasidze, S. Pääbo, A. Ryan, N.
Takezaki, G. Weiß, and V. Wiebe for helpful discussion. This study was supported by grants from theJapanese Society for the Promotion of Science toH.O., and Max Planck Society funds to M.S.
LITERATURE CITED
Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR,
Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier
PH, Smith AJ, Staden R, Young IG. 1981. Sequence and organization of the human mitochondrial genome. Nature 290:457–
465.
Aris-Brosou S, Excoffier L. 1996. The impact of population expansion and mutation rate heterogeneity on DNA sequence polymorphism. Mol Biol Evol 13:494 –504.
Ballinger SW, Schurr TG, Torroni A, Gan YY, Hodge JA, Hassan
K, Chen K-H, Wallace DC. 1992. Southeast Asian mitochondrial DNA analysis reveals genetic continuity of ancient Mongoloid migrations. Genetics 130:139 –152.
Bertranpetit J, Sala J, Calafell F, Underhill PA, Moral P, Comas
D. 1995. Human mitochondrial DNA variation and the origin ofBasques. Ann Hum Genet 59:63– 81.
Betty DJ, Chin-Atkins AN, Croft L, Sraml M, Easteal S. 1996.
Multiple independent origins of the COII/tRNA(Lys) intergenic
9-bp mtDNA deletion in Aboriginal Australians. Am J Hum
Genet 58:428 – 433.
Burckhardt F, von Haeseler A, Meyer S. 1999. HvrBase: compilation of mtDNA control region sequences from primates. Nucleic Acids Res 27:138 –142.
Calafell F, Underhill P, Tolun A, Angelicheva D, Kalaydjieva L.
1996. From Asia to Europe: mitochondrial DNA sequence variability in Bulgarians and Turks. Ann Hum Genet 60:35– 49.
Chu JY, Huang W, Kuang SQ, Wang JM, Xu JJ, Chu ZT, Yang
ZQ, Lin KQ, Li P, Wu M, Geng ZC, Tan CC, Du RF, Jin L. 1998.
Genetic relationship of populations in China. Proc Natl Acad
Sci USA 95:11763–11768.
Comas D, Calafell F, Mateu E, Perez-Lezaun A, Bertranpetit J.
1996. Geographic variation in human mitochondrial DNA control region sequence: the population history of Turkey and its
relationship to the European populations. Mol Biol Evol 13:
1067–1077.
Comas D, Calafell F, Mateu E, Perez-Lezaun A, Bosch E, Martinez-Arias R, Clarimon J, Facchini F, Fiori G, Luiselli D,
Pettener D, Bertranpetit J. 1998. Trading genes along the Silk
Road: mtDNA sequences and the origin of Central Asian populations. Am J Hum Genet 63:1824 –1838.

Corte-Real HB, Macaulay VA, Richards MB, Hariti G, Issad MS,
Cambon-Thomsen A, Papiha S, Bertranpetit J, Sykes BC. 1996.
Genetic diversity in the Iberian Peninsula determined frommitochondrial sequence analysis. Ann Hum Genet 60:331–350.
Ding Y-C, Wooding S, Harpending HC, Chi H-C, Li H-P, Fu Y-X,
Pang J-F, Yao Y-G, Yu J-GX, Moyzis R, Zhang Y-P. 2000.
Population structure and history in East Asia. Proc Natl Acad
Sci USA 97:14003–14006.
Di Rienzo A, Wilson AC. 1991. Branching pattern in the evolutionary tree for human mitochondrial DNA. Proc Natl Acad Sci
USA 88:1597–15601.
Francalacci P, Bertranpetit J, Calafell F, Underhill PA. 1996.
Sequence diversity of the control region of mitochondrial DNA
in Tuscany and its implications for the peopling of Europe.
Am J Phys Anthropol 100:443– 460.
Ginther C, Corach D, Penacino GA, Rey JA, Carnese FR, Hutz
MH, Anderson A, Just J, Salzano FM, King MC. 1993. Genetic
variation among the Mapuche Indians from the Patagonian
region of Argentina: mitochondrial DNA sequence variation
and allele frequencies of several nuclear genes. In: Pena SD,
Chakraborty R, Epplen JT, Jeffreys J, editors. DNA fingerprinting: state of the science 67. Basel, Switzerland. p 211–219.
Graven L, Passarino G, Semino O, Boursot P, Santachiara-Benerecetti S, Langaney A, Excoffier L. 1995. Evolutionary correlation between control region sequence and restriction polymorphisms in the mitochondrial genome of a large Senegalese
Mandenka sample. Mol Biol Evol 1995;12:334 –345.
Guo Z, Zheng SP, Sugimoto C, Wang YL, Zheng H-Y, Takasaka T,
Kitamura T, Guo J, Yogo Y. 2001. JC virus genotypes in northwestern China: implications for its population history. Anthropol Sci 109:203–212.
Handt O, Meyer S, von Haeseler A. 1998. Compilation of human
mtDNA control region sequences. Nucleic Acids Res 26:126 –129.
Harris DR. 1996. The origins and spread of agriculture and pastoralism in Eurasia: an overview. In: Harris DR, editor. The
origins and spread of agriculture and pastoralism in Eurasia.
London: UCL Press. p 552–573.
Horai S, Murayama K, Hayasaka K, Matsubayashi S, Hattori Y,
Fucharoen G, Harihara S, Park KS, Omoto K, Pan IH. 1996.
mtDNA polymorphism in East Asian populations, with specialreference to the peopling of Japan. Am J Hum Genet 59:579 –590.
Kolman CJ, Bermingham E, Cooke R, Ward RH, Arias TD, Guionneau-Sinclair F. 1995. Reduced mtDNA diversity in the
Ngobe Amerinds of Panama. Genetics 140:275–283.
Kolman CJ, Sambuughin N, Bermingham E. 1996. Mitochondrial
DNA analysis of Mongolian populations and implications forthe origin of New World founders. Genetics 142:1321–1334.
Krings M, Salem AE, Bauer K, Geisert H, Malek AK, Chaix L,
Simon C, Welsby D, Di Rienzo A, Utermann G, Sajantila A,Pääbo S, Stoneking M. 1999. mtDNA analysis of Nile River
Valley populations: a genetic corridor or a barrier to migration?
Am J Hum Genet 64:1166 –1176.
Lee SD, Shin CH, Kim KB, Lee YS, Lee JB. 1997. Sequencevariation of mitochondrial DNA control region in Koreans. Forensic Sci Int 87:99 –116.
Melton T, Clifford S, Martinson J, Batzer M, Stoneking M. 1998.
Genetic evidence for the proto-Austronesian homeland in Asia:
mtDNA and nuclear DNA variation in Taiwanese aboriginal
tribes. Am J Hum Genet 63:1807–1823.
Meyer S, Weiss G, von Haeseler A. 1999. Pattern of nucleotide
substitution and rate heterogeneity in the hypervariable regions I and II of human mtDNA. Genetics 152:1103–1110.
Mountain JL, Hebert JM, Bhattacharyya S, Underhill PA, Ottolenghi C, Gadgil M, Cavalli-Sforza LL. 1995. Demographic history of India and mtDNA-sequence diversity. Am J Hum Genet
56:979 –992.
Nei M, Tajima F, Tateno Y. 1983. Accuracy of estimated phylogenetic trees from molecular data. II. Gene frequency data. J
Mol Evol 19:153–170.
Oota H, Settheetham-Ishida W, Tiwawech D, Ishida T, Stoneking
M. 2001. Human mtDNA and Y-chromosome variation is cor-

mtDNA HOMOGENEITY IN ASIA
related with matrilocal versus patrilocal residence. Nat Genet
29:20 –21.
Perez-Lezaun A, Calafell F, Comas D, Mateu E, Bosch E, Martinez-Arias R, Clarimon J, Fiori G, Luiselli D, Facchini F,
Pettener D, Bertranpetit J. 1999. Sex-specific migration patterns in Central Asian populations, revealed by analysis of
Y-chromosome short tandem repeats and mtDNA. Am J Hum
Genet 65:208 –219.
Piercy R, Sullivan KM, Benson N, Gill P. 1993. The application of
mitochondrial DNA typing to the study of white Caucasian
genetic identification. Int J Legal Med 106:85–90.
Pult I, Sajantila A, Simanainen J, Georgiev O, Schaffner W,
Pääbo S. 1994. Mitochondrial DNA sequences from Switzerland reveal striking homogeneity of European populations. Biol
Chem Hoppe Seyler 375:837– 840.
Redd AJ, Stoneking M. 1999. Peopling of Sahul: mtDNA variationin aboriginal Australian and Papua New Guinean populations.
Am J Hum Genet 65:808 – 828.
Redd AJ, Takezaki N, Sherry ST, McGarvey ST, Sofro AS,
Stoneking M. 1995. Evolutionary history of the COII/tRNALys
intergenic 9 base pair deletion in human mitochondrial DNAs
from the Pacific. Mol Biol Evol 12:604 – 615.
Richards M, Corte-Real H, Forster P, Macaulay V, WilkinsonHerbots H, Demaine A, Papiha S, Hedges R, Bandelt HJ, Sykes
B. 1996. Paleolithic and Neolithic lineages in the European
mitochondrial gene pool. Am J Hum Genet 59:185–203.
Saitou N, Nei M. 1987. The neighbor-joining method: a new
method for reconstructing phylogenetic trees. Mol Biol Evol
4:406 – 425.
Saitou N, Omoto K, Du C, Du R. 1994. Population genetic study
in Hainan Island, China. II. Genetic affinity analyses. Anthropol Sci 102:129 –147.
Sajantila A, Lahermo P, Anttinen T, Lukka M, Sistonen P, Savontaus ML, Aula P, Beckman L, Tranebjaerg L, Gedde-Dahl T,
Issel-Tarver L, DiRienzo A, Pääbo S. 1995. Genes and languages in Europe: an analysis of mitochondrial lineages. Genome Res 5:42–52.
Seielstad MT, Minch E, Cavalli-Sforza LL. 1998. Genetic evidence for a higher female migration rate in humans. Nat Genet
20:278 –280.
Semino O, Passarino G, Oefner PJ, Lin AA, Arbuzova S, Beckman
LE, De Benedictis G, Francalacci P, Kouvatsi A, Limborska S,
Marcikiae M, Mika A, Mika B, Primorac D, Santachiara-Benerecetti AS, Cavalli-Sforza LL, Underhill PA. 2000. The genetic
legacy of Paleolithic Homo sapiens sapiens in extant Europeans: a Y chromosome perspective. Science 290:1155–1159.
Shields GF, Schmiechen AM, Frazier BL, Redd A, Voevoda MI,
Reed JK, Ward RH. 1993. mtDNA sequences suggest a recent

153

evolutionary divergence for Beringian and northern North
American populations. Am J Hum Genet 53:549 –562.
Stone AC, Stoneking M. 1998. mtDNA analysis of a prehistoric
Oneota population: implications for the peopling of the New
World. Am J Hum Genet 62:1153–1170.
Su B, Xiao J, Underhill P, Deka R, Zhang W, Akey J, Huang W,
Shen D, Lu D, Luo J, Chu J, Tan J, Shen P, Davis R, CavalliSforza L, Chakraborty R, Xiong M, Du R, Oefner P, Chen Z, Jin
L. 1999. Y-Chromosome evidence for a northward migration ofmodern humans into Eastern Asia during the last Ice Age.
Am J Hum Genet 65:1718 –1724.
Sykes B, Leiboff A, Low-Beer J, Tetzner S, Richards M. 1995. The
origins of the Polynesians: an interpretation from mitochondrial lineage analysis. Am J Hum Genet 57:1463–1475.
Tajima F. 1989. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595.
Tamura K, Nei M. 1993. Estimation of the number of nucleotide
substitutions in the control region of mitochondrial DNA in
humans and chimpanzees. Mol Biol Evol 10:512–526.
Torroni A, Schurr TG, Cabell MF, Brown MD, Neel JV, Larsen M,
Smith DG, Vullo CM, Wallace DC. 1993a. Asian affinities andcontinental radiation of the four founding Native American
mtDNAs. Am J Hum Genet 53:563–590.
Torroni A, Sukernik RI, Schurr TG, Starikorskaya YB, Cabell
MF, Crawford MH, Comuzzie AG, Wallace DC. 1993b. mtDNA
variation of aboriginal Siberians reveals distinct genetic affinities with Native Americans. Am J Hum Genet 53:591– 608.
Vigilant L, Pennington R, Harpending H, Kocher TD, Wilson AC.
1989. Mitochondrial DNA sequences in single hairs from asouthern African population. Proc Natl Acad Sci USA 86:9350 –
9354.
Vigilant L, Stoneking M, Harpending H, Hawkes K, Wilson AC.
1991. African populations and the evolution of human mitochondrial DNA. Science 1991 253:1503–1507.
Ward RH, Frazier BL, Dew-Jager K, Pääbo S. 1991. Extensive
mitochondrial diversity within a single Amerindian tribe. Proc
Natl Acad Sci USA 88:8720 – 8724.
Watson E, Bauer K, Aman R, Weiss G, von Haeseler A, Pääbo S.
1996. mtDNA sequence diversity in Africa. Am J Hum Genet
59:437– 444.
Wells RS, Yuldasheva N, Ruzibakiev R, Underhill PA, Evseeva I,
Blue-Smith J, Jin L, Su B, Pitchappan R, Shanmugalakshmi S,
Balakrishnan K, Read M, Pearson NM, Zerjal T, Webster MT,
Zholoshvili I, Jamarjashvili E, Gambarov S, Nikbin B, Dostiev
A, Aknazarov O, Zalloua P, Tsoy I, Kitaev M, Mirrakhimov M,
Chariev A, Bodmer WF. 2001. The Eurasian heartland: a continental perspective on Y-chromosome diversity. Proc Natl
Acad Sci USA 98:10244 –10249.