The biased distribution of D-M174 bears the different possible inferences of the human population prehistory in view of the origin and migratory pattern in East Asia. The hypothesis of northern origin of D-M174 is not supported by our data because D-M174 is rare in Central Asian populations (Table 1) and the few Central Asian D-M174s are all located at the peripheral positions of the Y-STR network (Figure 3). Our data also disapproves the notion of Indian origin since no D-M174 was detected in the 996 individuals across India. The sporadic occurrence of D-M174 in northeastern Indians (two D-M174s in 232 individuals tested) is because those populations are in fact Sino-Tibetan speaking populations (Table 1). The lack of gene flow between Tibet and India is likely due to the efficient geographic separation by the Himalayas .
On the other hand, the aborigines living on Andaman Island are genetically isolated in view of their Y chromosome haplotypes. Though phenotypically different from other Southeast Asian populations, the Andaman Islanders posses most of the major East Asian specific Y chromosome lineages including D-M174, O3-M122 and O2-M95, a strong indication of a relic Paleolithic population . Also, the Daic and Hmong-Mien speaking populations are ancient southern populations in view of linguistic and archaeological evidences . The network analysis indicates a clear divergence of D1-M15 between northern (Tibeto-Burman) and southern (Daic and Hmong) populations (Figure 3). Hence, the alternative explanation of northern origin of D-M174 is unlikely considering the absence of YAP+ in North Asia  and the sporadic appearance of D-M174 in Central Asia . Consequently, the southern origin of D-M174 can be established, which is consistent with the proposed initial settlement of modern humans in mainland Southeast Asia and the migration pattern of other Y chromosome lineages [8, 9, 13].
There were studies arguing against the southern origin of East Asian, in which higher gene diversity was observed in northern populations compared with southern populations [14, 30]. As we discussed in our previous report, the data from Karafet et al.  suggested a false impression of the high diversity of northern populations without taking the recent admixture from Central Asia into consideration . The study of Xue et al.  has the similar drawback though both Y-SNP and Y-STR data were used. In Xue et al (2006), the high gene diversity was claimed for Mongolian, Uygure and Manchurian, and all of them have recorded recent extensive admixture with Central Asian and Han Chinese populations . In addition, the southern populations studied in Xue et al. (2006) were limited and the within population bottleneck effect caused by long-time geographic isolation might have a great impact on gene diversity estimation. When plenty southern populations were studied, we observed a higher diversity in those populations compared with the northern populations [8, 9].
The gene diversity based on the STR data in the southern populations is comparable with those in the northern populations. Tibetan has the highest diversity (0.525 ± 0.294), followed by Daic (0.484 ± 0.272), Japanese (0.419 ± 0.239) and Hmong Mien (0.347 ± 0.206). Gene diversity of other East Asian populations was not calculated due to small sample size. The higher diversity in Tibetan is largely due to the much larger effective population size of D-M174 in Tibetan compared with other populations. Tibetan and Japanese lived in two geographically far away regions and their D-M174 lineages belong to two different sub-haplogroups. These two sub-haplogroups all have a short-distanced and star-like network structure, which indicates a long-term local existence and recent population expansion (Figure 3). It should be noted that the estimation of gene diversity is subject to potential bias, e.g. the age difference of the D-M174 sub-lineages. The finding of two DE* in Tibet, which was only observed in Africa, supports the antiquity of D-M174 and suggests that the D-M174 lineage is among the earliest modern human settlers in East Asia. Additionally, the biased distribution of D-M174 and its ancient coalescent time suggests an independent Paleolithic migration of modern humans in East Asia.
Our previous data on the O3-M122 lineage suggested a prehistorically northward migration (about 25,000–30,000 years ago) of modern humans in East Asia, which explains the current phylogeography of the major East Asian specific Y chromosome lineages (O3-M122, O2-M95 and O1-M119) [8, 9, 13]. However, the data on D-M174 cannot be explained by the hypothesized migration pattern. Firstly, D-M174 is rare in the central part of eastern Asia, especially in Han Chinese populations. Though this could be explained by genetic drift, assuming D-M174 moving along with O3-M122 during the proposed northward migration, the prevalence of D-M174 in Tibet and Japan requires recurrent mutations or independent random enrichment of D-M174, which is unlikely. An independent earlier northward migration is more reasonable in explaining the current distribution of D-M174 in East Asia. We speculate that due to the later northward migration of O3-M122 and the Neolithic expansion of Han Chinese, the trace of the D-M174 migration in the heartland of East Asia was wiped out by the later and likely much larger migration of O3-M122. The current peripheral distribution pattern of D-M174 in East Asia is consistent with the proposed notion. Also, the age estimation supports that the northward migration of D-M174 may predate the migration of O3-M122.
The East African megadroughts (about 135–75 thousand years ago) during the early late-Pleistocene was suggested compelling modern humans out of Africa . And the early modern human could occupy coastal areas and exploited the near-shore marine food resource by that time . Then, modern humans was suggested expanding along the tropical coast, and the earliest modern human fossil found out of Africa was about 100,000 years ago . The period of 80,000–10,000 years ago during the last glacial might have a huge impact on modern human migration, and the sea level had fallen 50–200 meters below present , which resulted in larger dry lands and possibility for human migration between currently separated lands by ocean, e.g. between Japan and the mainland.
Human fossil records and previous genetic data suggested that the earliest modern human settlement in East Asia likely occurred less than 60,000 years ago [8, 9, 13, 21, 35]. For example, the oldest Australian fossil (Lake Mungo 3) was dated about 45,000 ± 3,000 – 62,000 ± 6,000 years ago [36, 37], and the mitochondrial DNA and Y chromosome analysis of current Australian ethnic populations suggested the colonization of Australia about 50,000–70,000 years ago . Our age estimation of the D-M174 lineages is consistent with this notion though there might be independent migrations of modern humans into East Asia and into Australia .
The estimated ages of the D-M174 lineages are older than those previously reported based on both Y chromosome and mtDNA variations in East Asia [8, 9, 21]. To see whether it is over-estimated, using the same method, we calculated the divergence time between DE* and E-M40. The estimated age is 27,176 years, which is much younger than the D-M174 lineage, but consistent with the previous estimation (27,800–37,000 years ago) . Hence, the antiquity of D-M174 likely reflects the true prehistory of human populations in East Asia. The age estimation model developed by Zhivotovsky (2001) is not sensitive to effective population size and recent population expansion though the effect of population substructure cannot be totally ruled out. The antiquity of D-M174 was also supported by a previous study in which the origin of D-M174 was estimated more than 50,000 years ago .
The divergence time of haplogroup D is about 60,000 years ago, considering the wide though fragmented geographic distribution of D-M174, the proposed Paleolithic migration would be the first northward population movement of modern humans after their initial settlement in southern East Asia. As the last glacial occurred during 80,000–10,000 years ago, the northward migration of D-M174 is consistent with the proposed notion that modern humans might exploit the food of "Mammoth Steppe" . Besides the later population expansion, the cold weather during the last glacial may also contribute to the current fragmented distribution of D-M174. Interestingly, a recent archaeological finding supported that modern humans explored the Tibetan plateau about 30,000–40,000 years ago, which is much earlier than previously suggested , but consistent with our hypothesis. The after-glacial sea level rise eventually led to the separation between Japan and the main continent, which explains the relic distribution of D-M174 in current Japanese populations. The archaeological data suggested that the initial colonization of modern humans in Japan occurred about 30,000 years ago [41, 42], consistent with our age estimation of D2-M57 (37,678 ± 2,216 years ago). Taken together, the current Tibetan and Japanese populations are probably the admixture of two ancient populations represented by D-M174 and O3-M122 respectively [7, 10, 16].