Mait Metspalu; Toomas Kivisild; Ene Metspalu; Jüri Parik; Georgi Hudjashov; Katrin Kaldma; Piia Serk; Monika Karmin; Doron M Behar; M Thomas P Gilbert; Phillip Endicott; Sarabjit Mastana; Surinder S Papiha; Karl Skorecki; Antonio Torroni; Richard Villems

“ Recent advances in the understanding of the maternal and paternal heritage of south and southwest Asian populations have highlighted their role in the colonization of Eurasia by anatomically modern humans. ”

“ The spread of haplogroup R2 in Europe is restricted to a few populations in the Volga basin where it is represented by nodal haplotypes and by a region-specific subclade characterized by the HVS-I motif 16037–16172 [37] . The coalescence estimate of this sub-clade is 11,400 ± 9,000 ybp. However, its wide error range prevents us from drawing any firm conclusions.
To summarize, the West and South Asian phylogeography of haplogroups W, U7 and R2 can be viewed as a genetic continuum that spans from the Near East into India, extending north into Central Asia. ”

“ A large-scale immigration – carrying these haplogroups – could have introduced a substantial fraction of the diversity already present within the putative source areas. This would explain the deep coalescence times of these haplogroups in India, while their actual arrival could have occurred later. Alternatively, the coalescence estimates may indeed reflect a deeper autochthonous history of these mtDNA clades in India. It is worthwhile to stress that while in India the share of U7, R2 and W in the West Eurasian-specific mtDNAs mounts to nearly a third, in Iran it stays below 15%. ”

“ We also compared the mtDNA variation in India and Iran with that of Europe, China, and Thailand. The overall aim was to improve our understanding of the origins and composition of the Indian and Iranian gene pools and to determine the nature and the extent of gene flow between these regions. Through the analyses of the genetic variation of extant Southwest and South Asian populations we took an endeavor to envisage the exodus of anatomically modern humans from Africa. ”

“ With the exception of the diverse set of largely Indian-specific R lineages, the most frequent mtDNA haplogroup in India that derives from the phylogenetic node N is haplogroup W [19] . The frequency peak of haplogroup W is 5% in the northwestern states – Gujarat, Punjab and Kashmir. Elsewhere in India its frequency is very low (from 0 to 0.9%) (Table 2) forming a significant spatial cline (Figure 4) .
At 15% among the caste and 8% among the tribal populations haplogroup U is the most frequent sub-clade of R in India (Table 12, see Additional file 7) . ”

“ Awaiting further information from complete mtDNA sequences, we defined haplogroup M18 by using the transversion at np 16318. This star-like cluster (Figure 9) is spread at low frequencies across India, with the exceptions of the very north and the coast of the Arabian Sea (Figure 2, panel M18) . The high incidence (33%) of the M18 nodal haplotype among the Austro-Asiatic speaking Lodha of West Bengal (Table 10, see Additional file 5) suggests a possible founder effect in this population. ”

“ In relatively small and isolated groups (e.g. tribal groups) random genetic drift might seriously affect the haplogroup frequencies, which may become uninformative when a whole region (e.g. state) is considered (e.g. M18 among the Lodha, see below) . Therefore, the tribal data were excluded from the haplogroup isofrequency maps calculation. When illustrating the spread of mtDNA haplogroups native to West Eurasia, East Eurasia and India (Figure 11, panel D) we present these data as pie diagrams. The respective sample size and origin are indicated adjacent to the diagrams. ”

“ Most numerous sub-groups of macro-haplogroup N in India are the Indian-specific variants of the phylogenetic node R including haplogroups R5, R6, U2 (a, b, c) [ [6] , [19] , [20] .
The overwhelming majority of the Iranian mtDNAs have been shown to lie in the West Eurasian domain of the global human mtDNA pool [20] , [21] . Here we focus on the analysis of mtDNA lineages that are shared between Indians and Iranians and bear signals of pre-Holocene expansion in the region. ”

“ In Central Asia the frequency of haplogroup W stays below 2%.
Many European populations are lacking haplogroup U7 [7] , but its frequency climbs over 4% in the Near East and up to 5% in Pakistan, reaching nearly 10% level in Iranians (Table 9, see Additional file 4) . In India, haplogroup U7 frequency peaks at over 12% in Gujarat, in the westernmost state of India, while for the whole of India its frequency stays around 2%. ”

“ Furthermore, the lack of L3 lineages other than M and N (indeed, L3M and L3N) in India is more consistent with the African launch of haplogroup M. On the other hand, one also observes that: i) M1 is the only variant of haplogroup M found in Africa; ii) M1 has a fairly restricted phylogeography in Africa, barely penetrating into sub-Saharan populations, being found predominantly in association with the Afro-Asiatic linguistic phylum – a finding that appears to be inconsistent with the distribution of sub-clades of haplogroups L3 and L2 that have similar time depths. ”

“ In the western States of India and in Pakistan their share is greater, reaching over 30% in Kashmir and Gujarat, nearly 40% in Indian Punjab, and peaking, expectedly, at approximately 50% in Pakistan (Table 11, see Additional file 6, Figure 11, panel A) . These frequencies demonstrate a general decline (SAA p < 0.05 Figure 4) towards the south (23%, 11% and 15% in Maharashtra, Kerala and Sri Lanka, respectively) and even more so towards the east of India (13% in Uttar Pradesh and around 7% in West Bengal and Bangladesh) . ”

“ MtDNA sequence variation in a total of 796 Indian samples most of which are held in a collection at Newcastle University [42] was analyzed. The samples cover a wide geographical range that spans from Himachal Pradesh in the north, Sri Lanka in the south, West Bengal in the east and Gujarat in the west (Table 1) .
Tribal populations constitute 15% of the total sample size. The Lodha (n = 56) live mostly in the western part of Midnapore district of West Bengal where they are also known as Kheria or Kharia. Their total population size was ~59000 according to the 1981 census. ”

“ Thus, mtDNA data are consistent with an ancestral origin of the Tibeto-Burman speaking tribal populations outside (east of) India in the neighboring Tibet and Myanmar [ [23] , [41] .
Haplotype sharing between populations
The majority (70%) of the 1136 mtDNA haplotypes found among continental Indians (including Pakistan and Bangladesh) are singletons and 41% of those that occur more than once are restricted to a single population. Only a few haplotypes are shared among five or more populations. ”

“ The corrected value is comparable to the M2 frequency (>3%) in tribal populations speaking Indo-European languages of Punjab and Uttar Pradesh, but is significantly lower than its frequency (>14%) among the Dravidic-speaking tribal groups of Andhra Pradesh (Table 8, see Additional file 3) .
Language families present today in India, such as Indo-European, Dravidic and Austro-Asiatic, are all much younger than the majority of indigenous mtDNA lineages found among their present-day speakers at high frequencies (see Additional file 9) . ”

“ Circle areas are proportional to haplotype frequencies. Variant bases of the HVS-I are numbered as in (Anderson et al. 1981) minus 16,000 and shown along links between haplotypes. The diagnostic R5 coding region marker 8594 is shown in bold and numbered as in (Anderson et al. 1981) . Character changes are specified only for transversions. ”

“ U7 is more predominant in Iran, Pakistan, northwestern India and the Arabian peninsula, while W is more frequent in the western Near-East, Anatolia and the Caucasus. The coalescence ages of the Indian- and Iranian-specific U7 clades suggest that the time-window of this continuum was closed by ca. ”

“ Macaulay, V & Torroni, A (2003) , Extensive female-mediated gene flow from sub-Saharan Africa into near eastern Arab populations, vol. 72, pp. 1058–1064, 1262959810.1086/374384, pmid:12629598, DOI 10.1086/374384 1 2 Tambets, K; Kivisild, T; Metspalu, E; Parik, J; Kaldma, K; Laos, S; Tolk, H-V; Gölge, M; et al. (2000) , The topology of the maternal lineages of the Anatolian and Trans-Caucasus populations and the peopling of the Europe: some preliminary considerations, Cambridge: Cambridge University Press, pp. ”

“ Facchini, F; et al. (1998) , Trading genes along the silk road: mtDNA sequences and the origin of Central Asian populations, vol. 63, pp. 1824–1838, 983783510.1086/302133, pmid:9837835, DOI 10.1086/302133 ↑ Sambrook, J; Fritsch, EF & Maniatis, T (1989) , Molecular cloning: a laboratory manual., (2 ed.) , Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press ↑ Kaessmann, H; Heissig, F; von Haeseler, A & Paabo, S (1999) , DNA sequence variation in a non-coding region of low recombination on the human X chromosome, vol. ”