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Keywords:

  • BK virus;
  • human migration;
  • northeast Asia;
  • phylogenetic analysis

ABSTRACT

  1. Top of page
  2. ABSTRACT
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

BKV is widespread among humans, infecting children asymptomatically and then persisting in renal tissue. Based on the serological or phylogenetic method, BKV isolates worldwide are classified into four subtypes (I–IV), with subtypes I and IV further divided into several genetically-distinct subgroups. Since, similarly to JCV, a close relationship exists between BKV lineages and human populations, BKV should be useful as a marker to trace human migrations. To elucidate ancient human migrations in northeast Asia, urine samples were collected from immunocompetent elderly patients in Shanghai, China; Anyang, South Korea; and various locations in Japan. Partial and complete BKV genomes from these samples were amplified and sequenced using PCR, and the determined sequences were classified into subtypes and subgroups by phylogenetic and SNP analyses. In addition, based on an SNP analysis, the major subtype I subgroup (I/c) was classified into two subdivisions, I/c/Ch and I/c/KJ. The distribution patterns of BKV subgroups and subdivisions among the three regions were compared. Some aspects of the subgroup and subdivision distribution were more similar between Korea and Japan, but others were more similar between China and Korea or between China and Japan. Based on these findings, we inferred various northeast Asian migrations. Most of the JCV-based inferences of northeastern Asian migrations were consistent with those based on BKV, but the previously suggested migration route from the Asian continent to the Japanese archipelago seemed to need revision.

List of Abbreviations: 
BKV

BK polyomavirus

EDTA

ethylenediaminetetraacetic acid

BP

bootstrap probability

JCV

JC polyomavirus

NJ

neighbor-joining

PCR

polymerase chain reaction

SNP

single nucleotide polymorphism

BKV was originally isolated in 1971 from the urine of a renal allograft recipient (1) and is ubiquitous in essentially all human populations worldwide (2). Asymptomatic infection with this virus occurs during early childhood and leads to its life-long persistence in the kidney (3). Renal BKV infection is usually subclinical (3). Diseases caused by BKV infection are linked to a decline in immunologic activity (4); for example, BKV may cause graft dysfunction and graft loss in renal transplant recipients undergoing immunosuppression (5). BKV has four subtypes (I to IV) distinguishable by immunological and genotyping methods and circulating independently in the human population (2). BKV is mainly transmitted horizontally within a local community (6).

Recently, we found that, if highly sensitive PCR is performed with highly concentrated urinary DNA, BKV DNA sequences could frequently be amplified from the urine of non-immunocompromised individuals (7). Using this method, we amplified BKV sequences from urine samples collected around the world, and conducted phylogeographic studies with the obtained BKV sequences. These studies divided subtype I (the most prevalent subtype throughout the world) and subtype IV (the second-most prevalent subtype with a biased distribution toward Asia and Europe) into subgroups, each having unique geographic distribution, as described below. Subtype I is divided into four subgroups (I/a, I/b1, I/b2 and I/c), each of which has a unique geographic distribution pattern: I/a is most prevalent in Africa, I/b1 in Southeast Asia and China, I/b2 in Europe, and I/c in northeast Asia (8–10). Subtype IV is subdivided into six subgroups (IV/a1, IV/a2, IV/b1, IV/b2, IV/c1 and IV/c2) based on phylogenetic analyses (11). Most subtype IV subgroups, excluding c2, are found in distinct areas of East Asia, but c2 is prevalent mainly in Mongolia and Europe, suggesting that the subtype IV of BKV now prevalent in modern humans is derived from a virus that infected ancestral Asians (11).

The geographic distribution patterns of subtype-I and -IV subgroups suggest a close relationship between BKV and human populations. Indeed, co-migration of BKV and human populations has recently been shown by identifying similar distribution patterns for BKV subtypes and subgroups for Europeans and European-Americans (12). Thus, it can be assumed that, similarly to JCV (13–15), BKV could serve as a means of tracing human migrations on earth. To elucidate ancient human migrations in northeast Asia, here we compared the patterns of distribution of BKV subtypes and subgroups in Shanghai, China; Anyang, South Korea; and various locations in Japan. A previous study by Zheng et al. (10) has shown that BKV subtype profiles are roughly similar among the three countries, subtype I occurring at the highest rates followed by subtype IV. Therefore, a more detailed comparison of BKV lineages among the three countries is needed to gain an insight into the dispersals of northeastern Asians. In this study, we subdivided subtype I into four subgroups (I/a, I/b1, I/b2 and I/c) and subtype IV into six subgroups (IV/a1, IV/a2, IV/b1, IV/b2, IV/c1 and IV/c2). In addition, we sub-classified subgroup I/c into two subdivisions, I/c/Ch and I/c/KJ. We hoped that comparison of the distribution patterns of BKV subgroups and subdivisions among the three countries would allow us to make inferences regarding the dispersals of northeast Asians.

MATERIALS AND METHODS

  1. Top of page
  2. ABSTRACT
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Urine samples

Urine samples were collected in various geographic regions of Japan (Fukuoka, Hirosaki, Kazuno, Koromogawa, Nagareyama, Nara and Okinawa), Shanghai, China, and Anyang, South Korea (Fig. 1). The Chinese specimens were collected from non-immunosuppressed patients at the Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Korean specimens from healthy Koreans inhabiting Anyang, Gyeonggi-do; and the Japanese specimens from general patients without immunosuppression in various regions of Japan. The Chinese and Korean specimens were collected in this study, while the Japanese specimens had been collected previously (16, 17). The urine donors were native inhabitants of each region aged 60 years or older. All urine specimens were collected with informed consent.

image

Figure 1. Map showing the geographic regions of urine collection.

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DNA extraction

Urine was subjected to differential centrifugation to generate two pellets, PPT-I containing cell-associated viruses and PPT-2 containing cell-free viruses, as previously described (12). These pellets were resuspended in 1.3 ml of 10 mM Tris-HCl and 10 mM EDTA (pH 7.6) and were processed as previously described (12). PPT-1 were used to extract DNA in the Chinese and Korean specimens, and PPT-2 were used to extract DNA from the samples from Japan. It had previously been confirmed that identical BKV DNA sequences are detected in PPT-1 and PPT-2 from the same urine samples (12).

Amplification and sequencing of partial genomes of BKV

Using PCR, 287-bp and 470-bp VP1 regions of BKV were amplified from the DNA samples extracted from urine as described previously (8, 11). The 287-bp region contained the whole effective sequence within the previously used 327-bp typing region (18). The 470-bp region spanned nt 1731–2200 in the BKV (TW-3) genome (19) and contained multiple SNP among various subtype IV subgroups. Amplified fragments were sequenced as described (11, 12).

Amplification and sequencing of the entire genome of BKV

The entire BKV genome was PCR-amplified and sequenced as previously described (20).

Phylogenetic analysis

The typing-region sequences of BKV determined in this study and those reported previously (10, 19, 21, 22), together with that of SA12 (a baboon polyomavirus closely related to BKV) (23), were aligned using the CLUSTAL W program (24). The complete BKV DNA sequences determined in this and previous studies (10, 11, 19, 21, 22), together with that of SA12, were aligned similarly. Phylogenetic relationships among DNA sequences were evaluated using the NJ method (25). NJ analysis was performed by Kimura's 2-parameter distance method (26) using the baboon polyomavirus SA12 sequence as an out-group, and the phylogenetic tree was visualized using the NJplot program (27). To assess the confidence level of the phylogenetic tree, BP were estimated with 1000 bootstrap replicates (28).

Statistical analysis

Statistical analysis was performed using the χ2 test or Fisher's exact test. The significance level was set at 5%.

RESULTS

  1. Top of page
  2. ABSTRACT
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Classification of BKV isolates based on 287-bp typing-region sequences

We amplified and sequenced 287-bp typing regions from the urine of non-immunocompromised individuals in Shanghai, China (n= 78) and Anyang, South Korea (n= 68) (sites of sample collection are shown in Fig. 1). We constructed an NJ phylogenetic tree (25) from these sequences (Table 1), together with 17 reference sequences (Table 2). According to the resultant phylogenetic tree (Fig. 2), the BKV isolates in the two geographic regions were classified into four major clusters, previously designated subtypes I to IV (8, 10, 18), with BP ranging from 82% (for subtype III) to 100% (for subtype I), allowing unequivocal classification of the BKV isolates in the Chinese and Korean samples into subtypes I to IV.

Table 1.  BKV isolates whose complete or typing DNA sequences were analyzed in this study
Geographic regionIsolates for which typing DNA sequences were analyzedIsolates for which complete DNA sequences were analyzed
  1. Sequences have been deposited in DDBJ/EMBL/GenBank under accession numbers AB465043 to AB465188.

  2. Sequences have been deposited in DDBJ/EMBL/GenBank under accession numbers AB365158 to AB365178 and AB464953 to AB464963.

Shanghai, ChinaSHA-1 to -78SHA-4, -7, -9, -10, -13, -19, -22, -23, -25, -28, -30, -38, -40, -41, -43, -47, -55, -56, -62, -70, -72, -78
Anyang, South KoreaANY-1 to -68ANY-2, -3, -7, -13, -29, -32, -33, -38, -56, -57, -63
Table 2.  BKV isolates whose complete and VP1-region DNA sequences were used as the reference sequences in the phylogenetic analysis
Subtype/subgroupIsolateClinical stateGeographic originGenBank accession no.§
  1. Isolates used only for the phylogenetic analysis based on complete genome sequences, while the other isolates were used not only for the phylogenetic analysis based on complete genome sequences but also for the phylogenetic analysis based on VP1 region sequences.

  2. AT, acute tonsillitis; BMT, bone marrow transplant; NIS, non-immunosuppressed; RT, renal transplant; SLE; systemic lupus erythematosus; WAS, Wiskott-Aldrich syndrome.

  3. §Accession numbers for complete genome sequences are shown (VP1 region sequences were excised from complete genome sequences).

I/aDUNWASUSANC_001538
I/aKEN-1NISKenyaAB263926
I/b1DikATThe NetherlandsAB211369
I/b1WWRTSouth AfricaAB211371
I/b2JLBMTThe NetherlandsAB211370
I/b2FNL-12NISFinlandAB263918
I/cMTSLEJapanAB211372
I/cTW-1RTJapanAB211381
I/cRYU-2RTJapanAB211377
IIETH-3NISEthiopiaAB263916
IIGBR-12NISUKAB263920
IIIASPregnantUKM23122
IIIKOM-3BMTJapanAB211386
IV/a1VNM-7NISVietnamAB269869
IV/a1PHL-8NISPhilippinesAB269859
IV/a2RYU-3RTJapanAB211389
IV/a2MMR-1NISMyanmarAB269841
IV/b1THK-8RTJapanAB211390
IV/b1TW-3RTJapanAB211391
IV/b2KOM-2BMTJapanAB211387
IV/b2JPN-15NISJapanAB269834
IV/c1MON-1NISMongoliaAB269846
IV/c1SWC-1NISChinaAB269863
IV/c2GRC-4NISUKAB269830
IV/c2ITA-4NISItalyAB269833
image

Figure 2. NJ phylogenetic tree classifying BKV isolates from Shanghai, China and Anyang, Korea into subtypes and subgroups. The 287-bp typing-region sequences detected in Shanghai, China (n= 68) and Anyang, Korea (n= 78) (Table 1) plus 17 reference sequences (Table 2) were used to reconstruct this NJ phylogenetic tree, using the corresponding sequence of the baboon polyomavirus SA12 as the out-group. The phylogenetic tree was visualized using the NJplot program. Subtypes and subtype-I subgroups are indicated to the right of the tree. Isolates shown in bold were also used for phylogenetic analysis based on complete genome sequences (Fig. 3). Symbols for isolates are described in Table 1. The isolates used as references are shown in italics. The numbers at nodes are BP (%) obtained for 1000 replicates (shown only for major nodes).

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We identified some sub-clusters of subtype I which were judged to correspond to subgroups I/a, I/b1, I/b2 and I/c from the reference sequences representing individual subgroups (Fig. 2). However, the BP for these sub-clusters were not significantly high (57%, 56%, 78%, and <50% for I/a, I/b1, I/b2 and I/c, respectively). In addition, two subtype I isolates, SHA-38 and -49, were not included in any subgroups. Therefore, to sub-classify the Chinese and Korean isolates belonging to subtype I, we also used SNP within the 287-bp VP1 region (9). The SNP patterns of most isolates, including the two Chinese isolates (SHA-38 and -49) not sub-classified by the phylogenetic analysis (Fig. 2), were identical with that of I/b1, I/b2 or I/c, which allowed sub-classification of these isolates.

Phylogenetic analysis based on complete genome sequences

To ascertain the branching of BKV based on partial BKV genome sequences, the complete DNA sequences of 22 isolates from Shanghai, China and 11 isolates from Anyang, South Korea were determined, and an NJ phylogenetic tree was constructed from these sequences (Table 1) together with the 25 reference sequences (Table 2). In the phylogenetic tree (Fig. 3), BKV sequences were divided into three major clusters with high BP (100%), corresponding to subtypes I, (II and III), and IV. Subtypes (II and III) were further divided into two sub-clusters with high BP (100%), subtype I was subdivided into four sub-clusters with high BP (100%), corresponding to I/a, I/b1, I/b2 and I/c, and subtype IV was subdivided into six subclusters with high BP (89–100%), corresponding to IV/a1, IV/a2, IV/b1, IV/b2, IV/c1 and IV/c2. In short, phylogenetic analysis based on complete sequences confirmed both the classification of the BKV isolates into subtypes and the sub-classification of subtypes I and IV into subgroups.

image

Figure 3. NJ phylogenetic tree showing relationships among complete BKV DNA sequences. The complete sequences determined in this study (Table 1) plus 25 reference sequences (Table 2) were used to reconstruct the NJ phylogenetic tree. The baboon polyomavirus SA12 was used as the out-group. The phylogenetic tree was visualized using the NJplot program. Subtypes and subgroups are indicated to the right of the tree. Symbols for isolates are described in Table 1. The isolates used as references are shown in italics. The numbers at nodes are BP (%) obtained for 1000 replicates.

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Distribution of BKV subtypes in northeast Asia

Table 3 shows the numbers of isolates classified as belonging to each subtype for Shanghai, China; Anyang South Korea; and various regions of Japan (subtype identification was based on phylogenetic analysis, as noted above). The Japanese data were taken from a reference (17). The findings can be summarized as follows.

Table 3.  BKV subtype profiles in various regions of northeast Asia
Geographic regionNo. (%) of isolates classified as indicated subtypesTotal
IIIIIIIV
  1. *P < 0.05 vs. various regions, Japan (as compared to subtype I).

Shanghai, China49 (63)0029 (37)*78 (100)
Anyang, Korea51 (75)02 (3)15 (22)68 (100)
Various regions, Japan191 (73)06 (2)66 (25)263 (100)
  • 1
    Subtype I was prevalent in all the three geographic areas, with incidences varying from 63% to 75%.
  • 2
    Subtype IV occurred at the second-highest frequency in all of the areas. The detection rate for subtype IV as compared with subtype I was significantly higher in Shanghai, China than in various regions of Japan (P < 0.05).
  • 3
    Subtypes II and III rarely occurred in any of the geographic areas.

Distribution of subtype I subgroups in northeast Asia

Table 4 shows the numbers of isolates classified as belonging to each subtype I subgroup for the three geographic areas (subgroup identification was based on both phylogenetic and SNP analyses, as noted above). The findings can be summarized as follows.

Table 4.  Distribution of subtype I subgroups in various regions of northeast Asia
Geographic regionNo. (%) of isolates classified as indicated subgroupTotal
I/aI/b1I/b2I/cUC
  1. Unclassified.

  2. *P < 0.01 vs. Anyang, Korea or various regions, Japan (as compared to I/c).

Shanghai, China013 (27)*1 (2)35 (71)049 (100)
Anyang, Korea003 (6)48 (94)051 (100)
Various regions, Japan010 (5)5 (3)174 (91)2 (1)191 (100)
  • 1
    In each geographic area, subgroup I/c [the subgroup prevalent in northeast Asia (10)] occurred at the highest incidence, ranging from 71% to 94%.
  • 2
    I/b1 [the subgroup prevalent in Southeast Asia and South China (10)] occurred at the second highest rate (27%) in Shanghai, China, while it was not found in Anyang, South Korea (0%) and rarely occurred at various sites in Japan (5%). The differences in the incidence of I/b1, as compared to I/c, between Shanghai, China and Anyang, South Korea and between Shanghai, China and various sites, Japan were all statistically significant (P < 0.01).
  • 3
    Subgroup I/a [the subgroup prevalent in Africa (10)] and subgroup I/b2 [the subgroup prevalent in Europe (10)] did not occur, or rarely occurred, in each geographic area.

Distribution of subtype IV subgroups in northeast Asia

In the geographic areas studied, there were many subtype IV isolates that were not sub-classified based on complete genomic sequences. To sub-classify these isolates, we used the 470-bp VP1 region that contains SNP with which to sub-classify subtype IV isolates (11). The number of isolates classified into each subgroup of the IV subtype is shown in Table 5 for each geographic area. The findings are summarized as follows.

Table 5.  Distribution of subtype IV subgroups in various regions of northeast Asia
Geographic regionNo. (%) of isolates classified as indicated subgroupTotal
IV/a1IV/a2IV/b1IV/b2IV/c1IV/c2
  1. *P < 0.05 vs. Anyang, Korea and P < 0.01 vs. various regions, Japan (as compared to IV/b2).

  2. **P < 0.01 vs. Shanghai, China, and P < 0.05 vs. various regions, Japan (as compared to IV/b2).

  3. ***P < 0.05 vs. Shanghai, China (as compared to IV/a2).

Shanghai, China2 (10)*4 (19)02 (10)13 (62)021 (100)
Anyang, Korea00**011 (85)2 (15)013 (100)
Various regions, Japan08 (25)10 (31)***14 (44)0032 (100)
  • 1
    In Shanghai, China, IV/c1 occurred at the highest rate (62%), and IV/a2 occurred at the second highest rate (19%); the other subgroups (i.e. IV/a1, IV/b1, IV/b2 and IV/c2) rarely occurred or were not detected.
  • 2
    In Anyang, South Korea, IV/b2 occurred at the highest rate (85%), with rare detection (15%) of IV/c1; the other four subgroups (i.e. IV/a1, IV/a2, IV/b1 and IV/c2) were not detected.
  • 3
    For various sites, Japan, three subgroups (IV/a2, IV/b1 and IV/b2) occurred at similar rates (25–44%). All seven isolates classified as belonging to subgroup IV/a2 were detected in Okinawa, the southernmost island of Japan.
  • 4
    The above-noted distribution patterns for subtype IV subgroups were significantly different between geographic areas (P<0.01 or P<0.05) (Table 5).

Geographic distribution of the subdivisions of subgroup I/c

The phylogenetic tree (Fig. 3) based on complete genome sequences revealed a cluster of eight Korean isolates together with two reference sequences from Japan (BP, 74%). This observation suggested that the I/c subgroup might be classified into a few regionally distinct subdivisions. To detect nucleotide polymorphisms that can distinguish such I/c subdivisions, we examined the aligned complete I/c sequences detected in the three northeast Asian countries, and found that nucleotide polymorphisms at three positions (nucleotides 503, 1767, and 2361; the nucleotide numbering is that of a typical I/c isolate, TW-1) were useful to subdivide I/c. Two major combinations of nucleotide at the three positions were (G, A, C) and (C, C, G) (Table 6), with some minor combinations probably derived from the major ones by single nucleotide substitution. A subdivision of I/c carrying the (G, A, C) combination together with two minor combinations probably derived from (G, A, C) was designated I/c/Ch, since this subdivision was mainly found in China (Table 6). Similarly, a subdivision of I/c carrying the (C, C, G) combination and three minor combinations probably derived from (C, C, G) was designated I/c/KJ, since it was mainly found in Korea and Japan (Table 6).

Table 6.  Distribution of the subdivisions of subgroup I/c in various regions of northeast Asia
SubdivisionNucleotides at indicated positionsGeographic areasNo. of isolates
nt 503nt 1767nt 2361
  1. The nucleotide numbering is that of a typical I/c isolate, TW-1.

I/c/ChGACChina (Shanghai)12
    Japan (Nagareyama, Okinawa)4
     4
 GATKorea (Anyang)1
 CACKorea (Anyang)2
I/c/KJCCGKorea (Anyang)8
    Japan (northeast, Nara, Fukuoka, Okinawa)13
     13
 GCGJapan (Nara)1
 CCAJapan (Okinawa)2
 CCCJapan (Okinawa)1

DISCUSSION

  1. Top of page
  2. ABSTRACT
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Ancient human migrations from the Korean Peninsula to the Japanese Archipelago

It is generally accepted that modern Japanese were developed from two distinct ethnic groups; the Jomon people (“Jomonese”) who colonized Japan in the Neolithic period, and later immigrants (the Yayoi immigrants) who came from the Asian continent during the Aeneolithic Yayoi and the prehistoric Kofun periods (reviewed in 29). Using the JCV method, Zheng et al. (30) examined the route by which the Yayoi immigrants migrated to the Japanese Archipelago. Two JCV lineages, MY and CY, are mainly distributed in the Japanese Archipelago, with CY linked to the Yayoi immigrants and MY linked to the Jomonese (16, 31). Based on nucleotide variations in the JCV genome, Zheng et al. (30) classified CY into two sub-lineages, CY-a and CY-b, and found that the ratio of CY-a to CY-b diverged among northeast Asian populations, with CY-a more abundant in Chinese and Japanese populations, and CY-b more abundant in Koreans. This finding, suggesting a closer affinity between Chinese and Japanese than between Koreans and Japanese, was considered to provide support for the hypothesis that the Yayoi immigrants migrated directly from China to Japan rather than through the Korean Peninsula (30). However, an alternative hypothesis: that the Yayoi immigrants came from the Korean Peninsula, has been suggested by studies in different disciplines, that is, archaeology (29) and genetic anthropology (32), and therefore the hypothesis remained to be confirmed by other approaches using symbiotic microorganisms, which could include BKV.

In this study, we found that Korea and Japan shared two features with respect to the distribution of BKV lineages. First, a subdivision (I/c/KJ) of subgroup I/c was mainly detected in Korea and Japan, whereas another subdivision (I/c/Ch) occurred predominantly in China. Second, of various subtype IV subgroups, IV/b2 occurred predominantly or at the highest rate in Korea and Japan, whereas it rarely occurred in China. Since BKV co-migrated with the human race (12), the present findings on BKV lineages support a migration route through the Korean Peninsula (29, 32).

If the BKV lineage data obtained in this study accurately represent the population history of northeast Asia, it follows that the ratio of CY-a to CY-b is not necessarily a reliable marker with which to evaluate the affinity among human populations. These sub-lineages of CY were estimated to have been separated about 10 000 years ago (30), and it is conceivable that, after such a long time, the ratio of CY-a to CY-b in present-time populations may have significantly drifted from the original ratio.

Other northeast Asian migrations based on BKV data

Various northeast Asian migrations inferred on the basis of the present findings are illustrated in Figure 4. Migration from Korea to Japan was inferred based on the findings regarding subdivision I/c/KJ and subgroup IV/b2 as described in the preceding section. Other migrations shown in Figure 4, except for the one based on IV/b1 (see below for a discussion on the origin of IV/b1), were inferred by assuming that migration occurred from the homeland (i.e. the major domain of a subgroup or subdivision) to an adjacent area where the subgroup or subdivision was detected less frequently. These included a migration from China to Korea inferred based on subdivision I/c/Ch or subgroup IV/c1; a migration from China to Japan based on subdivision I/c/Ch, subgroup I/b1 or subgroup IV/a2; and a migration from Southeast Asia to China based on subgroup I/b1, subgroup IV/a1 or subgroup IV/a2.

image

Figure 4. Migrations of northeast Asian populations carrying various BKV lineages as inferred from the findings of this study.(a)Migrations based on subtype I subgroups; (b)migrations based on subtype IV subgroups.

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We emphasize that the migrations from Southeast Asia to China and from China to South Japan, both based on BKV lineages (see above), are consistent with those based on JCV lineages, as explained in the following. A JCV lineage named SC is prevalent in South China and Southeast Asia. Saruwatari et al. (33), who conducted a detailed phylogeographic analysis of SC isolates worldwide, found that although isolates belonging to a sub-lineage (SC-f) of SC are widespread in the world, most non-SC-f isolates, (excluding SC-x spread in the Philippines), are restricted to an area of mainland Southeast Asia including Myanmar and Thailand. From these observations, they inferred that in an area of Southeast Asia including Myanmar and Thailand, an ancestral human population carrying proto-SC may have diverged into various populations, each carrying a distinct variant of SC, and that of these human populations, only two (those carrying SC-f and SC-x) migrated out of the area. Thus, based on SC-f, a migration from Southeast Asia to South China is inferred. In addition, since SC-f occurs in South Japan at a low frequency, a minor migration from China (probably Taiwan) to South Japan is also inferred.

Since IV/b1 has not been detected in geographic regions other than Japan, the origin of this subgroup remains unclear. As all subtype IV subgroups, excluding IV/b1, occur in the Asian continent, it seems reasonable to assume that IV/b1 originated in the continent and migrated from there to Japan. IV/b1 may have been associated with the indigenous people in Japan, the Jomonese, who are probably derived from the Upper Paleolithic northeast Asians (34), since no BKV lineage has been implicated with this ethnic group (17).

ACKNOWLEDGMENTS

  1. Top of page
  2. ABSTRACT
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

We thank Ayako Shibuya for excellent technical assistance. We are grateful to all the urine donors. This study was supported in part by grants from the Ministry of Health, Labor and Welfare, Japan.

REFERENCES

  1. Top of page
  2. ABSTRACT
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES
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