OPEN

Journal of Human Genetics (2016), 1–9
Ofﬁcial journal of the Japan Society of Human Genetics
www.nature.com/jhg

ORIGINAL ARTICLE

A partial nuclear genome of the Jomons who lived
3000 years ago in Fukushima, Japan
Hideaki Kanzawa-Kiriyama1,2,9, Kirill Kryukov3, Timothy A Jinam1,2, Kazuyoshi Hosomichi1,4,10, Aiko Saso5,6,
Gen Suwa5,6, Shintaroh Ueda6, Minoru Yoneda5, Atsushi Tajima7, Ken-ichi Shinoda8, Ituro Inoue1,4 andNaruya Saitou1,2,6
The Jomon period of the Japanese Archipelago, characterized by cord-marked ‘jomon’ potteries, has yielded abundant humanskeletal remains. However, the genetic origins of the Jomon people and their relationships with modern populations have notbeen clariﬁed. We determined a total of 115 million base pair nuclear genome sequences from two Jomon individuals (male andfemale each) from the Sanganji Shell Mound (dated 3000 years before present) with the Jomon-characteristic mitochondrial
DNA haplogroup N9b, and compared these nuclear genome sequences with those of worldwide populations. We found that the
Jomon population lineage is best considered to have diverged before diversiﬁcation of present-day East Eurasian populations,with no evidence of gene ﬂow events between the Jomon and other continental populations. This suggests that the Sanganji
Jomon people descended from an early phase of population dispersals in East Asia. We also estimated that the modern mainland
Japanese inherited o20% of Jomon peoples’ genomes. Our ﬁndings, based on the ﬁrst analysis of Jomon nuclear genome
sequence data, ﬁrmly demonstrate that the modern mainland Japanese resulted from genetic admixture of the indigenous Jomon
people and later migrants.
Journal of Human Genetics advance online publication, 1 September 2016; doi:10.1038/jhg.2016.110

INTRODUCTION
Genome-wide single-nucleotide polymorphism (SNP) data analyses1,2
support the dual-structure model3,4 for the formation of modern
Japanese populations, in which indigenous Jomon people admixed
with later migrants who brought rice agriculture. The Jomon culture
geographically ranged from Hokkaido to the Okinawa islands, and theJomon people inhabited the Japanese Archipelago from ~ 16000 to2500 years before present (YBP).5,6 The origins and phylogenetic
relationships of the Jomon people, however, are still elusive.
Ancient DNA sequences of the Jomon people provide direct
evidence of their genetic characteristics. Mitochondrial DNA(mtDNA) sequences of the Jomon people and their haplotypes havebeen determined for many individuals.7–12 Haplogroup N9b, whose
frequency is generally low in modern East Eurasians,13,14 was found to
be quite frequent in the mtDNA of the Jomons.9–11 This suggests a
long-term isolation of the Jomons from continental populations.
However, inferring human population history only from mtDNA
data are insufﬁcient because of their limited genetic information.
Thanks to new technologies, it is now possible to analyze nuclear
genome sequences of ancient human remains15–23 and those ofmodern human individuals.24 We therefore determined the nuclear
genome sequences of two Jomon individuals and compared them withavailable data so as to infer the origin of modern Japanese.
MATERIALS AND METHODSDNA extraction, library preparation, sequencing and sequence
mapping
We extracted DNA from the teeth of Jomon individuals kept at the University
Museum, the University of Tokyo. These samples were originally excavated at
the Sanganji Shell Mound in the 1950s.25 This shell mound is located in thenorthern part of Fukushima Prefecture, Tohoku region, Japan (Supplementary
Figure 1). The mtDNA haplotypes of four Sanganji Jomon individuals werepreviously genotyped.11 We designate two DNA extracts of the Sanganji
131421-3 individual, one extracted by Kanzawa-Kiriyama et al.,11 and theother newly extracted for this study, as A1 and A2, respectively. The DNA
extract from sample 131464 is referred to as B. The new DNA extract (A2) was
prepared using Adachi et al.’s12 protocol with some modiﬁcations(Supplementary Methods S1). Three DNA libraries for A1, A2 and B wereprepared from the DNA solution extracted from their molars (Supplementary
Methods S1). The GAIIx platform was used for library A1, and 120-bp pairedend sequence reads were generated following the manufacturer’s protocol.

1
Department of Genetics, School of Life Science, SOKENDAI (Graduate University for Advanced Studies), Mishima, Japan; 2Division of Population Genetics, National Institute of
Genetics, Mishima, Japan; 3Department of Molecular Life Science, School of Medicine, Tokai University, Isehara, Japan; 4Division of Human Genetics, National Institute of
Genetics, Mishima, Japan; 5The University Museum, The University of Tokyo, Tokyo, Japan; 6Department of Biological Sciences, Graduate School of Science, The University ofTokyo, Tokyo, Japan; 7Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan and
8
Department of Anthropology, National Museum of Nature and Science, Tsukuba, Japan
9Current address: Department of Anthropology, National Museum of Nature and Science, Tsukuba, Japan.
10Current address: Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan.
Correspondence: Professor N Saitou, Division of Population Genetics, National Institute of Genetics, 1111 Yata, Mishima 411-8540, Japan.
E-mail: saitounr@nig.ac.jp
Received 16 May 2016; revised 22 July 2016; accepted 26 July 2016

Jomon nuclear genome
H Kanzawa-Kiriyama et al2
We used Hiseq2000 to generate 100-bp paired-end sequence reads for libraries
of DNA samples A2 and B. Sequence mapping was then conducted(Supplementary Methods S2). PCR duplicates, which were produced duringlibrary preparations, were removed using MarkDuplicates from Picard program(https://broadinstitute.github.io/picard/) as well as PickingBases, newly
developed by one of us (KK) (see Supplementary Perl Scripts S1).

DNA authenticity checking and error rate estimation
To clarify the authenticity of the mapped sequence reads, we checked thefrequency of post-mortem misincorporation and depurination, which arecharacteristic of ancient DNA. As it is difﬁcult to remove all modern human
DNA contaminations that come from reagents and experimental rooms, it isalso essential to estimate the frequency of endogenous DNA from Jomon
individuals. To estimate the frequency of contamination, we focused onsequence reads mapped to mtDNA and estimated ratio of mismatched reads
to each mtDNA haplogroup, which were previously classiﬁed into N9b11(Supplementary Methods S3).
We estimated error rate using the method of Reich et al.16 Genome
sequences of chimpanzee,26 14 present-day humans19,24 and two ancientindividuals19,22 (see Supplementary Table S1 for their list) were used toestimate the degree of post-mortem changes in the Sanganji Jomon. The ﬁrst
and last few bases of sequence reads that harbor many post-mortem changes
speciﬁc to ancient genomes were removed in the Denisovan,19 Altai
Neanderthal22 as well as Sanganji Jomon sequences using bamUtil (http://
genome.sph.umich.edu/wiki/BamUtil) to minimize their effect in downstream
statistical analyses. For the Sanganji Jomon sequences, different numbers ofbases were trimmed in each sample based on transition rates; in sample A1, we
trimmed the ﬁrst and last 10 bases because this sample had more transversion
substitutions at the end of sequence reads compared with sample A2 and B,
whereas we trimmed only ﬁve bases in sample A2 and B. For the archaic
humans, we trimmed ﬁve bases. See Supplementary Methods S4 for details.

Principal component analysis (PCA)
SNPs observed in modern human populations were used to examine thegenetic relationship between individuals through PCA. Four data sets from the1000 Genomes Project Consortium,24 the Human Genome Diversity Project(HGDP),27 the HapMap Project28 and the Japanese Archipelago Human
Population Genetics Consortium data,1 were used. First, three ﬁlters,
Hardy–Weinberg equilibrium (HWE) po1e-10, minor allele frequencyo0.01,
genotype call rateo0.95, were applied using PLINK.29 These ﬁlters wereapplied in all downstream analyses. For each individual, we randomly chose
one nucleotide at each site and duplicated it to create homozygous diploid
genotypes to compensate for the fact that no heterozygous/homozygous states
could be ascertained in the Jomon genome data due to the low coverage.30 This
step evens the data condition between modern samples and ancient samples.
We then merged the modern human data sets with the Sanganji Jomon
sequence. We used only sites where the Jomon genome sequences hadcoverage. Finally, we performed PCA based on the overlapping SNPs by using
the smartpca program in the EIGENSOFT.31

Allele-sharing analysis
Because the number of individuals is limited in the Sanganji Jomon data set, it
is not suitable to interpret population differentiation between Jomon andmodern populations based on Fst values. We investigated the frequency of allele
sharing between Sanganji Jomon individuals and modern populations to infer
the degree of genetic similarity between them. We used array-based genomewide SNP data, and the original genotype data were used for the analysis insteadof the homozygous diploid data sets for PCA. For the Sanganji Jomon,
we created homozygous diploid genotypes to compare those with modern
populations by using PLINK-freq option. We counted the number of sharedallele with Sanganji Jomon and calculated the proportion of shared allele ineach individual. We then took the average and calculated the standard error ineach population.
Journal of Human Genetics

Phylogenetic analysis
We used TreeMix,32 neighbor-joining33 and Neighbor-Net34 to estimate
phylogenetic relationships among ancient and modern humans(Supplementary Methods S5). All substitution sites data or transversion-only
substitution sites data were used for the analysis, and we compared those results
to check the effect of post-mortem changes. For HGDP data,27 we used the all
substitution data only because of limited number of SNPs. In addition, we used
modern human genome data from Papuan and Karitiana16 and ancient humangenome from Mal’ta (MA1) dating to ~ 24 000 YBP,23 Ust’-Ishim dating to
45 000 YBP21 and Denisovans19 to the analyses.

D-statistics to detect gene ﬂow

D-statistics analysis16 can infer gene ﬂow without invoking demographic
models, and is based on the number of shared alleles between three individuals
of interest (H1, H2 and H3) and one outgroup (O). At any particular locus, thepattern ABBA is where H2 and H3 share the derived allele ‘B’, whereas H1 andO share the ancestral allele ‘A’. Conversely, BABA is where the derived allele isshared between H1 and H3 and the ancestral allele is shared between H2 andO. We basically used only transversion substitution sites to minimize errors inour data sets except for HGDP because of data limitation. The number of
BABA and ABBA patterns, nBABA and nABBA, is used to calculate the D-value
and Z-score with ADMIXtools.35 We added data of SGVP Malay population in
Singapore36 to HGDP data sets for the D-statistics analysis.

RESULTS
Dating, mapping and assignment of sequence reads
The Jomon pottery of the Sanganji Shell Mound site belong to the late
to ﬁnal Jomon period.25 The Jomon skeletal remains were dated by
one of us (MY) using the radiocarbon method to be ~ 3000 YBP(Supplementary Table S2), corresponding to the ﬁnal Jomon period.
The mapped sequence reads from three DNA libraries A1, A2 and B
covered 21, 39 and 58 million nucleotides (0.46–2.18%) of the humangenome build hg19, respectively (Supplementary Table S3). These low
ratio of endogenous human DNA are typically observed in ancient
samples.15,20 In the DNA library treated with two restriction enzymes,
the frequency of sequence reads mapped to hg19 was ~ 50% higher
than the frequency obtained from the untreated library (1.30% and0.87%, respectively). Many reads appear to be derived from bacteria,
but ~ 50% of the reads were not assigned uniquely to speciﬁc species
or groups in BLASTN (Supplementary Figure S2), consistent withprevious studies.15,20
We deposit all short read sequences produced for this study
to DDBJ Sequence Read Archive (http://trace.ddbj.nig.ac.jp/dra/).
Sequence data are available for download thorough SRA accession
number DRA004001.
Damage estimates and DNA sequence authenticity
Average DNA lengths of mapped sequences reads were 94.5, 102.2 and76.9 bp, respectively. Read length distribution for each library is shownin Supplementary Figure S3. From the ratio of sequence reads mapped
to X and Y chromosomes, we concluded that individuals A and B weremale and female, respectively. This identiﬁcation is consistent withmorphological observation of these individuals.25 We observed
characteristic features of ancient DNA degradation, including C to
T misincorporation at high frequencies in 3′ and 5′ ends and anincreased fraction of purines close to sequence read termini(Supplementary Figures S4 and S5, respectively), indicating that thosesequence reads most likely contain endogenous Jomon DNAs.
Sample A1, however, has more transversion substitutions than samples
A2 and B. We cannot explain the reason, but after mtDNA capturing
and the sequencing with MiSeq, the pattern disappeared.

Jomon nuclear genome
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Although contamination frequency (3.03%; 0.0–7.17%, 95%
conﬁdence interval) of DNA sample A2 based on captured mtDNA
sequence reads was low (Supplementary Results S1), the frequency(11.3%; 2.8–19.9%, 95% conﬁdence interval) based on simple shotgun
sequencing was high compared with the other two DNA samples. We
thus used sequence data for only samples A1 and B in the downstream
analyses to minimize the effect of the cross contaminations. Aftermerging the data of A1 and B for downstream analyses, ~ 77.7 million
nucleotide positions were available for analysis.
We estimated error rates in 16 modern/archaic humangenomes16,19,22 as well as in Sanganji Jomon. Although the error rateof the Sanganji Jomon sequence was 0.828–0.848% over all sites, theerror rate was only 0.011–0.015% in the transversion sites, which iscomparable with the rate in modern humans (Supplementary
Table S7). PickingBases (PB) removed more errors compared with
MarkDuplicates (Supplementary Table S7). We found more transition
substitutions (A/G or C/T) in Sanganji Jomon than in other modern
humans, which appears to be caused by post-mortem changes
characteristic of ancient DNA (Supplementary Tables S8-S9). We also
would like to note that Jomon-speciﬁc transversion substitutions(0.0129%) and unreported transversions in dbSNP 141(0.0113%)
were comparable (Supplementary Table S7). Similar values were also
observed in modern human data, and this comparison strengthens
the low error rate of the Sanganji Jomon nucleotide sequences.
Interestingly, the number of SNPs reported in dbSNP was small in
Sanganji Jomon compared with other non-Africans; for example, 4169
and 5270 in Sanganji Jomon and Han, respectively (Supplementary
Table S7). This observation is consistent with our expectation thatmany Jomon SNPs are unreported in dbSNP. We conﬁrmed thereliability of PB in PCA, and the result using PB are concordant withthat of MarkDuplicates, and are not biased (Figure 1a andSupplementary Figure S7). Because of smaller sequence error rates
of PB than that of MarkDuplicates, we used data sets treated with PB
for further analyses. In total, 28 288 sites were masked as N with PB.
Genetic relationship between Sanganji Jomon and other modern
and archaic humans
We investigated the genetic relationships between Sanganji Jomon andmodern humans from different parts of the world, including Africans,West Eurasians, East Eurasians, Native Americans and Sahulians37(descendants of people who migrated to Sahul land); see the map
shown in Supplementary Figure S1.
PCA. When worldwide populations are compared, PCA illustrates
the genetic similarity of Sanganji Jomon and East Eurasians comparedwith African, European, Sahulian and Native American peoples(Figure 1a, Supplementary Figures S7-S11). However, Sanganji Jomon
is located slightly closer to the center of the three major populationgroups in Figure 1a. This indicates the genetic uniqueness of Sanganji
Jomon among East Eurasians, and/or the effect of post-mortem
changes in ancient DNA, although the latter is unlikely because theresult using only transversion sites showed very similar results(Supplementary Figures S8 and S10). Next, we investigated the genetic
relationship between the Sanganji Jomon and East Eurasians. Comparison with 1000 Genomes Project24 East Asians (JPT (JapaneseTokyo), CHB (Han Chinese in Beijing), CHS (Southern Han
Chinese), CDX (Chinese Dai in Xishuangbanna, China) and KHV(Kinh in Ho Chi Minh City, Vietnam)) based on 46 158 SNP sites
show that the Sanganji Jomon is located quite apart from the othermodern East Eurasians, and modern Japanese are situated between
the Sanganji Jomon and continental East Eurasians (Figure 1b).

Although the Sanganji Jomon data were merged for sequence dataof A1 and B, the PCA plot location of the Sanganji Jomon was similar
to Figure 1b when A1 and B were independently analyzed(Supplementary Figure S13). We therefore surmise that the merged
data are reliable for further analyses. The uniqueness of the Sanganji
Jomon was also observed when only transversion sites were used
(Supplementary Figure S12), again indicating that the uniqueness was
not the result of post-mortem changes.
The comparison with the genome-wide SNP data of HGDP
populations27 also showed the unique status of the Sanganji Jomon,
who was positioned far apart from all modern East Eurasians in PC2
and PC3, although only 6864 SNPs were used. (Figure 2a,
Supplementary Figure S14). The uniqueness of the Sanganji Jomon
within East Eurasians is consistent with the results including
Europeans and Africans. When the Ainu, the mainland Japaneseand the Ryukyuan from the Japanese Archipelago1 and CHB28 werecompared with Sanganji Jomon, PC1 separated the Ainu and Sanganji
Jomon from the other populations (Figure 2b). The population closest
to the Sanganji Jomon was the Ainu, followed by the Ryukyuan andthen the mainland Japanese. It appears that PC1 corresponds to thedegree of genetic contribution from the Jomon people to the otherJapanese Archipelago populations, whereas PC2 separated the Ainu
from Sanganji Jomon. When the genomic data of 1000 Genomes
Project East Asians24 were included in the PCA analysis (Figure 2b),
PC3 separated the Ainu from the Sanganji Jomon (Supplementary
Figure S15).
Allele sharing analysis. Allele sharing analysis using 5392 SNP sites(Figure 3a) showed that the Ainu had the highest percentage of allele
sharing with the Sanganji Jomon, followed by the Ryukyuan, themainland Japanese and CHB, similar to the projection of PC1 in
Figure 2b. Using the HGDP East Eurasian data set with 7081 SNP sites(Figure 3b), the mainland Japanese had the highest allele sharing
with the Sanganji Jomon. Interestingly, southern East Eurasians (greenbars) had slightly higher allele-sharing percentages than northern East
Eurasians (blue bars), although we have to be careful with the effect of
post-mortem changes.
TreeMix analysis. We constructed maximum-likelihood population
trees (ML tree) using TreeMix to investigate the phylogenetic
relationship and the presence of admixture events between Sanganji
Jomon and other human populations. When three migration eventswere assumed, the gene ﬂow from Sanganji Jomon to JPT (modern
Japanese) appeared (Figure 4) (bootstrap probability = 42%). The
directionality of this gene ﬂow event was as expected, however, theinferred gene ﬂow from Karitiana to Mal’ta MA1 (Supplementary
Results S2; Supplementary Figures S16b-j and S17c-j), was in thereverse direction to what was reported by Raghavan et al.23 who used amuch larger sequence data. This result might have been caused byusing a relatively small SNP data set. We therefore used only modern
human data, and reran TreeMix. We used a much larger 0.7 million
SNP loci data. However, the resulting tree showed some anomalous
gene ﬂow directions; from Papuans to Denisovans (bootstrap probability = 98%) and CEU to Papuans (bootstrap probability = 86%),
whereas the tree topology was consistent with that of Figure 4 (seeSupplementary Figure S19). The reason for this anomaly may be thatsome ﬁltering steps between our analyses and Reich et al.16 and Meyer
et al.19 are different, and/or homozygous diploid genotypes inindividual genome (that is, Denisovan, Papuan and so on) were usedinstead of their original genotype, though gene ﬂow from Mal’ta MA1
to Karitiana correctly appeared in both all sites and transversion only
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Jomon nuclear genome
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Figure 1 Principal component analysis with genome sequence data. (a) Sanganji Jomon and 1000 Genomes Project worldwide humans based on 68 542
SNPs with PB. (b) Sanganji Jomon and 1000 Genomes Project East Eurasians based on 46 158 SNPs with PB.

when we add Mal’ta MA1, Karitiana and Ust’-Ishim to the large SNPloci data (data not shown).
Distance matrix-based analysis. We constructed neighbor-joining
trees (Figure 5a and Supplementary Figure S20) from distancematrices, and the Native American diverged after the divergence of
the Sanganji Jomon from the modern East Eurasians in these trees.
This is consistent with Figure 4, although the bootstrap probability tosupport this branching pattern was only 64% in Figure 5a. We also
drew a Neighbor-Net network using the same distance matrix(Figure 5b and Supplementary Figure S21). Major splits are consistent
with the neighbor-joining tree (Figure 5a), and split X clustered theSanganji Jomon and JPT. This split conﬁrms the admixed nature of
the mainland Japanese inferred from the PCA and TreeMix analyses.
See Supplementary Results S3 for more detailed analysis using
Neighbor-Net.
D-statistic analysis. In agreement with the PCA and TreeMix results,
the D-statistic test also suggested genetic afﬁnity of the Sanganji Jomon
with the East Eurasians, especially with the mainland Japanese,compared with non-East Eurasians (Figure 6a and b). This reﬂects
the genetic continuity between the Jomon and the mainland Japanese,and support the hypothesis of an early divergence of the Jomon withthe ancestor of modern East Eurasians (Supplementary Figure S23).
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See also Supplementary Results S4 for additional analyses using
D-statistics.
The genetic relationship between Sanganji Jomon and the archaic
humans were then investigated. Genetic afﬁnities between Neanderthal
and non-African, and between Denisovan and Sahulian werepreviously reported.15,16,19,22 The test of ((Sanganji Jomon, San), Altai
Neanderthal) implies genetic afﬁnity of the Jomon people with
Neanderthals, but the degree was not much different from the othernon-Africans (Supplementary Figure S31). Compared with the other
East Eurasians, Sanganji Jomon did not show additional similarities
with the Denisovans.
DISCUSSION
This is the ﬁrst study on the ancient nuclear genome of the Neolithic
hunter-gatherers who lived on the Japanese Archipelago. We observed
more post-mortem changes in the Sanganji Jomon sample than in
two other archaic human examples (~0.8% in Sanganji Jomon,
Supplementary Table S7). Environmental conditions (for example,
temperature, humidity, pH value, geochemical properties of soil) or
use of different sample treatments may affect the condition of theancient DNA. We did not treat the ancient DNA with uracil DNA
glycosylase and endonuclease VIII, which remove C to T misincorporation from the sequence reads. This is to reduce the numberof experimental steps so as to minimize the risk of contamination inJomon nuclear genome
H Kanzawa-Kiriyama et al5library preparations. We also chose to see the post-mortem damage
speciﬁc to ancient DNA to more clearly evaluate the ancient origin of
the extracted DNA. This may be the reason that the DNA damage washigh in Sanganji Jomon sequences.
PCA and phylogenetic analyses revealed the genetic relationships
between the Sanganji Jomon and the modern human populations that

Figure 2 Principal component analysis with genome-wide SNP data.
(a) Sanganji Jomon and HGDP East Eurasians based on 6864 SNPs with
PB. (b) Sanganji Jomon, individuals of three populations inhabiting theJapanese Archipelago (Ainu, mainland Japanese and Ryukyuan), andChinese Beijing (CHB) based on 5392 SNP sites with PB.

we compared. We found that Sanganji Jomon was genetically quitedistinct from the other modern East Eurasians. Our Jomon genotypes
are still mostly based on a single read per SNP site, whereas the 1000
Genomes Project data24 had at least 4–6 × coverage. We need to becareful about the effect of genotype error rate even if we use onlytransversion sites (error rate = 0.0129%). However, PCA plots using allsites (Figure 1 and Supplementary Figures S7 and S9) and those usingtransversion only (Supplementary Figures S8) are more or less thesame, and TreeMix trees using all sites (Figure 4 and Supplementary
Figures S16 and S18) and those using transversion only
(Supplementary Figure S17) also showed similar positions for the
Sanganji Jomon. Therefore, we believe that the phylogenetic relationship of the Sanganji Jomon can still be reliably estimated with
our data.
Some cranial metric and dental analyses suggested that the ancestral
population of the Jomon people originated from Southeast Asia,3,39–43
whereas other morphological analyses44,45 and mtDNA sequence data9
suggested that their ancestors were of Northeast Asian origin.
However, neither hypothesis was supported from our analysis using
direct Jomon nuclear genome sequences. Our results suggest that the
Jomon people were descendants of an ancestral East Eurasian
population prior to population diversiﬁcations recognizable today.
The possibility that the Sanganji Jomon ancestors diverged before
the Native Americans was also inferred through the maximumlikelihood tree, neighbor-joining tree, and the D-statistic tests, but
this is still inconclusive because of the small number of SNPs in theanalyses. However, all the results suggest a deep Jomon divergencewithin East Asia, close to the Native American split. The effect ofgenotype errors also need to be taken into account in interpreting theapparent deep divergence of the Jomon people. A relatively large
amount of genotype errors in the Jomon data set would induce theirlong tree branch and/or genetic similarity between the Jomon andoutgroups (for example, non-East Eurasians and archaic humans) as
artifacts, placing the Jomon closer to the root of outgroup-East
Eurasian splits and/or showing gene ﬂow between Jomon and thoseoutgroups. However, since we did not observe any of those artifacts,

Figure 3 Allele sharing between Sanganji Jomon and modern humans. Vertical line indicates the frequency of having the same allele with the Sanganji
Jomon. (a) Comparison with Japanese Archipelago populations and Chinese Beijing (CHB) based on 5392 SNP sites with PB, (b) comparison with HGDP
East Eurasians, Sahulians and Native Americans based on 7081 SNP sites with PB. Colors blue, green, brown and violet indicate northern East Eurasians,
southern East Eurasians, Sahulians and Native Americans, respectively.
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Figure 4 Phylogenetic analysis I. TreeMix tree with gene ﬂows. A comparison of Sanganji Jomon, 1000 Genomes Project worldwide populations, Papuan,
Karitiana, Mal’ta MA1, Ust’-Ishim and Denisovan based on 43 310 all sites. Denisovan was used as the outgroup, and three gene ﬂow events were
estimated. The tree was drawn by using MEGA6.38 Red colored values (only those higher than 90% are shown) are bootstrap probabilities (%) for theiradjacent internal branch. Arrows were manually added to this tree, and colors of migration weight (ratio of gene ﬂow) follow TreeMix outputs. Values insidearrows are the ratio of gene ﬂow. Bootstrap probabilities (%) of the gene ﬂow from Sanganji Jomon to JPT, Karitiana to the root of European and Mal’ta MA1,and LWK to European, estimated out of 1000 bootstrap replicate TreeMix outputs, are 42%, 86% and 0.4%, respectively.

Figure 5 Phylogenetic analysis II. Distance-based. A total of 15 519 transversion sites were used for computing distances. (a) Neighbor-joining tree.
(b) Neighbor-net network. Branches for populations starting with `B' were shortened for clarity.

and the inferred genotype error rate in the transversion-only sites(0.0129%) is quite small, it is unlikely that the Jomon was erroneously
located at the basal position of East Eurasians. The ages of the mostrecent common ancestors of mitochondrial DNA haplogroups N9b
and M7a (considered indigenous to Jomon and modern Japanese, andcalled the Jomon haplotype), were estimated to be 22 000 YBP and
23 000 YBP, respectively.10 These estimates also support a deep
divergence of the Jomon people.
We also examined whether the uniqueness of the Sanganji Jomon in
East Eurasia was the result of gene ﬂow from non-East Eurasians, but
the evidence for this was not suggested (Supplementary Figures S22,
S24 and S25). This indicates that the ancestor of the Sanganji Jomon
had been genetically isolated from continental populations after theirdivergence. However, our results do not deny a possibility of small
fraction of gene ﬂow between the Jomon people and the non-East
Eurasians, which might not be detected in the current study becauseof the small amount of the determined Jomon genome sequences.
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The TreeMix tree and the D-statistic tests also conﬁrm the lack of
non-East Eurasian contaminations in the Jomon data via reagents
because if there were such contamination during experiments, theeffect would be artiﬁcially detected as gene ﬂow in those analyses.
Genetic afﬁnity between modern East Eurasians and Melanesiancompared with Sanganji Jomon was inferred, but these results werealso ambiguous because of the data limitation. Further genomic
sequencing of Jomon genomes in future studies will clarify suchquestions.
Our results show that the populations genetically closest to Sanganji
Jomon are those that live on the Japanese Archipelago. The current
Japanese population is widely accepted to be a result of admixture ofindigenous Jomon and later migrant people, whereby the latter wereagricultural people that came from continental Asia into the JapaneseArchipelago probably via the Korean Peninsula during and after the
Yayoi era. Until now, this hybridization scenario has not been veriﬁed
directly at the genomic level. Our result based on PCA, TreeMix andJomon nuclear genome
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Figure 6 D-statistic tests of Sanganji Jomon and worldwide humans.
(a) Comparison of Sanganji Jomon, 1000 Genomes Project worldwide
populations, Mal’ta MA1 and Ust’-Ishim based on 15 549 transversion sites.
(b) Comparison with HGDP East Eurasians and Native Americans and SGVP
Malay population based on 7439 SNPs.

neighbor-joining trees, Neighbor-Net networks, and D-statistic tests
clariﬁed that the Jomon people genetically contributed to the modern
Japanese Archipelago populations. The genetic similarity would not be
explained by contamination from Japanese archipelago populations
during experiments, because the direction of gene ﬂow estimated in
TreeMix tree was from Jomon to JPT, not from JPT to Jomon(Figure 4), and the D((KHV or CHS, CHB) Jomon) value in
D-statistic tests (Figure 6a) was not negative with signiﬁcant Z-score(JPT was genetically closer to CHB than to CHS or KHV).
Furthermore, if there was contamination from modern Japanese, theJomon would be genetically closer to CHB than to CHS and KHV,
leading to negative D-values and probably signiﬁcant Z-scores.
Therefore, we can conclude that the modern Japanese Archipelago
populations are the admixture of the Jomon people and otherpopulations with genetic afﬁnities with modern Northeast Asians.
This result is consistent with the conclusion based on the genetic
analyses of modern human populations.1 However, it is difﬁcult to

pin-point the geographic origins of the candidate populations becauseof lack of genetic data of relevant ancient populations.
The amount of genetic contribution from the Jomon people variedamong the Japanese Archipelago populations (Figures 2b and 3a andSupplementary Figure S15). The Ainu and the Ryukyuan share morealleles with the Jomon than the mainland Japanese, suggesting smaller
genetic contributions from continental populations in those two
populations than for the mainland Japanese, in agreement withprevious ﬁndings.1,2,4,13,46–50 This supports the dual-structure modelof Hanihara,3,50 which is a widely accepted theory that explains thehistory of the three current populations that inhabit the JapaneseArchipelago, and which predicts that the mainland Japanese are more
admixed with agricultural continental people than the Ainu and the
Ryukyuan, with major admixture occurring in and after the Yayoi
period.
PC1 values of some Ainu individuals were similar to that ofSanganji Jomon, whereas PC2 separated the Ainu people from
Sanganji Jomon (Figure 2b). It is probable that the ancestors of the
Ainu people experienced admixture with other population(s) (forexample, continental population(s) not used in the current study) after
the Jomon period, and they are thus genetically differentiated from the
Jomon people.51 The candidate population is the Okhotsk people, who
inhabited the Northeastern costal area of the Hokkaido region, Japan,
from the 5th to 13th century. They were morphologically close tomodern southern Siberians such as the Nivkhi and Ulchi people,52–55
who were not included in the current study. Recent studies suggestthat the descendants of the Hokkaido Jomon people had admixed with
the Okhotsk people and became ancestors of the modern Ainu.56–59
Jinam et al.2 recently estimated the proportion of the Jomon
ancestry in the mainland Japanese using the f4-ratio test35 under aspeciﬁed phylogenetic scenario. The estimated proportion of Jomon
ancestry differs depending on the compared populations and were
within the range of 13–21%. Jinam et al.2 also used ADMIXTURE60
and found that the mainland Japanese was best explained by twoancestry components. One of them has very high proportions in many
Ainu individuals, and is considered to be Jomon ancestry if we assume
that the Ainu people are largely descendants of the Jomon. The
average proportion of this Jomon component in the mainland
Japanese was 17%, which is within the range of f4-ratio test results.2
The same genome-wide SNP data were also used for ABC analysis,
and the highest likelihood model estimated the admixture proportion
from the Jomon ancestry to the mainland Japanese to be 36%(22–53%, 95% conﬁdence interval).50 We used TreeMix for estimating
Jomon ancestry proportions in this study, and the frequency was 12%
as shown in Figure 4. We note that it is possible that the frequency
was underestimated if the Jomon people had some population
substructure and the northern Jomon including the Sanganji Jomon
only indirectly contributed to the modern Japanese, and/or if there arecontamination during experiments from the Japanese Archipelago
populations. Previously, the proportion of the Jomon component in
the modern mainland Japanese was estimated to be 35% based onpartial mtDNA sequences of modern human populations46 and
23–40% based on application of a demographic model of population
admixture.61 Although the Jomon admixture proportion is still
debatable, we would like to conclude that the Jomon component in
the mainland Japanese is probably lower than 20%.
One remaining question is whether or not the ancestors of the
Jomon people experienced any gene ﬂow with archaic humans. The
ancestor of modern humans who moved out of Africa admixed with
Neanderthals,15,22 whereas Denisovan DNA sequences were shown toshare some similarity with the modern East Eurasians and Sahulians,
Journal of Human Genetics

Jomon nuclear genome
H Kanzawa-Kiriyama et al8especially with Papuan, Melanesian, Australian Aboriginal andSoutheast Asian islanders.16,17,19,62 The result of D-statistic tests
implies that there was no additional gene ﬂow with archaic humans
observed in the Sanganji Jomon compared with the other East
Eurasians (Supplementary Figure S31).
In conclusion, this is the ﬁrst report describing the genetic
relationships between the prehistoric Jomon and modern and otherarchaic human populations based on nuclear genome sequences, andreveals new insights on population history in East Eurasia. This report
is a starting point for future studies.
CONFLICT OF INTEREST
The authors declare no conﬂict of interest.
ACKNOWLEDGEMENTS
We thank Drs Y Shirakibara, T Baba and K Yanagihara of National Institute of
Genetics for their kind permissions of using their experimental rooms,
Mr T Kakuda of National Museum of Nature and Science for helping DNA
extraction, Mrs M Mizuguchi for writing three perl scripts, and Mr I Babarinde
and Ms Nilmini Hettiarachchi of Saitou Laboratory at National Institute of
Genetics for helping computational analyses. We also thank Asian DNA
Repository Consortium for use of the genome-wide SNP data for the Ainu
population. This study was supported by a grant-in-aids of Ministry of
Education, Culture, Sports, Science and Technology (MEXT) of Japan toKS (25251043) and by SOKENDAI Strategic Interdisciplinary Research Project‘Comprehensive study on creation of genetic and cultural diversity throughmodern human dispersal’ to NS.

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