Genetic Origins of the Kalash People

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Genetic Origins of the Kalash People Nov 20, 2015 7:49:49 GMT

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Post by Admin on Nov 20, 2015 7:49:49 GMT

Figure 1 Population Structure and Isolation of the Kalash

(A) Geographic location of the three Pakistani villages where the Kalash samples were collected.

(B) Principal-component analysis (PCA) of Eurasian populations shows the first two components superimposed with the spatial kriging interpolation of the admixture coefficient of the Kalash genetic cluster. The proportion of admixture is indicated by color: orange represents the maximum level of admixture, and black represents the lowest. There is no gradient into the proportion of admixture with the Kalash cluster, suggesting a low level of gene flow between nearby populations and a high degree of isolation.

(C) Admixture analysis in which the lowest cross-validation error (k = 7) shows the unique Kalash cluster (dark green).

We assessed the genetic relatedness between three ancient genomes and modern human populations, including the Kalash, by computing outgroup f3 statistics. The measure circumvents potential bias from classical genetic relatedness tests, such as PCA (which has sample-size bias) and FST (which is sensitive to genetic drift that has occurred since divergence of the test populations), when using ancient genomes. According to outgroup f3 statistics, the Kalash share a high level of genetic drift with MA-1, a Paleolithic Siberian hunter-gatherer skeleton dated to ∼24,000 years ago, but not a very high level with La Braña 1, the Mesolithic European hunter-gatherer (skeletal remains dated to ∼7,000 years ago) or the European farmers represented by Ötzi, the Tyrolean Iceman dated to ∼5,300 years ago (Figure 3). Similar to Native Americans, the Kalash share a high proportion of genetic drift with MA-1. In comparison with other populations from Pakistan and India, the Kalash also share a higher proportion of genetic drift with La Braña 1 and Ötzi. The level of drift shared with La Braña 1 and Ötzi is comparable to that of other North European populations (Figure 3B). We also used TreeMix to estimate the proportion of Neandertal ancestry from the high-coverage archaic Altai Neandertal who lived ∼50,000 years ago. The jackknife estimate of Neandertal-to-Kalash gene flow was 2.4% ± 0.48%.

The Kalash represent a unique branch in the South Asian population tree and appear to be the earliest population to split from the ancestral Pakistani and Indian populations, indicating a complex scenario for population origins in the sub-continent rather than just the ancestral northern and southern Indian components identified previously.35 These Indo-European speakers were possibly the first migrants to arrive in the Indian sub-continent from northern or western Asia. This is supported by the higher level of shared genetic drift between the Kalash and the Paleolithic Siberian hunter-gatherer skeleton (MA-1) than between MA-1 and the other South Asian populations.

Figure 3 Shared Genetic Drift with Ancient Genomes

(A) Proportion of shared genetic drift (measured as f3 statistics) between extant world-wide HGDP-CEPH populations (including the Kalash) and the ancient Siberian hunter-gatherer (MA-1). The magnitude of the computed f3 statistics is represented by the graded heat key. The proportion of genetic drift shared between the Kalash and MA-1 is comparable to that shared between MA-1 and the Yakut, Native Americans, and northern European populations.

(B) Ternary plot of shared genetic drift with three ancient genomes: MA-1 (left), La Braña 1 (middle), and Ötzi, the Tyrolean Iceman (right). The high proportion of genetic drift shared between the Kalash and MA-1 is comparable to that shared between MA-1 and Native Americans. In comparison with other populations from South Asia, the Kalash also share a higher proportion of genetic drift with La Braña 1 and Ötzi.

Whereas the Kalash have recently been reported to have European admixture, postulated to be related to Alexander’s invasion of South Asia,6 our results show no evidence of admixture. Although several oral traditions claim that the Kalash are descendants of Alexander’s soldiers, this was not supported by Y chromosomal analysis in which the Kalash had a high proportion of Y haplogroup L3a lineages, which are characterized by having the derived allele for the PK3 Y-SNP and are not found elsewhere.7 They also have predominantly western Eurasian mitochondrial lineages and no genetic affiliation with East Asians.4

We observed that the Kalash share a substantial proportion of drift with a Paleolithic ancient Siberian hunter-gatherer, who has been suggested to represent a third northern Eurasian genetic ancestry component for present-day Europeans.36, 37 This is also supported by the shared drift observed between the Kalash and the Yamnaya, an ancient (2,000–1,800 BCE) Neolithic pastoralist culture that lived in the lower Volga and Don steppe lands of Russia and also shared ancestry with MA-1.36, 37 Thus, the Kalash could be considered a genetically drifted ancient northern Eurasian population, and this shared ancient component was probably misattributed to recent admixture with western Europeans.

We also looked at how this long-term separation, isolation, and low effective population size affected the patterns of genetic variation in the Kalash. One striking example is the frequency of the derived allele for rs4988235, which has been linked to lactose tolerance. The Kalash, like the MA-1, are fixed for the ancestral allele for this variant, whereas their neighbors in Pakistan have been observed to have moderate frequencies of the derived allele. Although this supports their long-term isolation, it is surprising in other ways because the Kalash have no reported lactose intolerance and indeed celebrate a “milk day” during their annual spring rituals.38 This suggests that there might be additional derived lactase-persistence alleles in the LCT-MCM6 (MIM: 601806) region in this population.

Another example is the extremely high frequency (93%) of the stop-gain ACTN3 variant (rs1815739) associated with normal variation in human muscle strength and speed.39 This variant was picked up as an outlier in the PBS test for selection in the Kalash. Simulations indicated that such a high frequency of the derived allele in the Kalash can only be obtained under a scenario that includes positive selection. The variant might be relevant in cardiovascular conditioning and muscle strength related to climbing up and down high mountain passes. Although ACTN3 has not been associated with adaptation to high altitude, RYR2, another gene with an intronic outlier variant (rs2992644) in PBS, has.40

It has been postulated that South Asia, which is now a densely occupied land, was encountered by the first populations of modern humans that ventured out of Africa more than 50,000 years ago. The exact route taken by these earliest settlers is not known, although it has been suggested that they traveled via a southern coastal route.41, 42 The genetically isolated Kalash might be seen as descendants of the earliest migrants that took a route into Afghanistan and Pakistan and are most likely present-day genetically drifted representatives of these ancient northern Eurasians. A larger survey that includes populations from their ancestral homeland in Nuristan, Afghanistan, would provide more insights into their unique genetic structure and origins and help explain the complex history of the peopling of South Asia.

www.cell.com/ajhg/fulltext/S0002-9297(15)00137-8

Last Edit: Sept 13, 2021 21:05:32 GMT by Admin

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Genetic Origins of the Kalash People Jan 22, 2019 3:53:38 GMT

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Post by Admin on Jan 22, 2019 3:53:38 GMT

The recent paper “The Kalash Genetic Isolate: Ancient Divergence, Drift, and Selection”, by Ayub et al1 (AJHG 2015, 96:1-9) suggests that the Kalash people of present-day Pakistan experienced “no detectable gene flow from their geographic neighbors in Pakistan or from other extant Eurasian populations” since their split from those populations over 8000 years ago. They note that this finding of apparent genetic isolation contradicts the results of Hellenthal et al2, who inferred DNA introgression dated to 910-220BCE in an overlapping sample of Kalash individuals. Hellenthal et al2 inferred the (unknown) source of this DNA to have genetic similarities to a wide range of modern-day groups from West Asia and Europe, including Germany-Austria and Turkey, for example. Ayab et al apply methods using two fundamental sources of information, which differ in the types of admixture they are designed to detect. The first source of information, leveraged by ALDER, a method developed in work involving several of us3, is unique patterns of linkage disequilibrium generated by admixture. Ayub et al claim that ALDER “showed no evidence of gene flow into the Kalash”1.

However, this is an error, as the ALDER results reported in their Table S4 show highly significant
evidence (p-value < 10-10) in the Kalash when using Armenia and Chamar as surrogates. Eight other
pairings of surrogates give p-values < 10-5. In all cases, the surrogate pairs include one group from
South Asia (Chamar, Kol) and the other from West Eurasia (Armenia, Adygei, Brahui, Hungarians,
Palestinians, Tuscans), consistent with admixture from a West Eurasian source as reported in 2.
The admixture date point estimates range from 92-125 generations ago (with standard errors < 20),
consistent to that inferred in Hellenthal et al using GLOBETROTTER (95% CI: 76-101 generations)2.
Indeed, the original ALDER paper also found a highly significant signal of mixture in the Kalash
(Table 1 of that paper)3.

.
The second source of information is based on tests for population mixture, as implemented in the
ADMIXTOOLS4 and TREEMIX5 software, that model allele frequency correlation patterns among
populations but not correlation patterns along the genome. The authors fail to detect a signal using
these methods, although previous work has shown that signals of population mixture using such
methods can be masked by the effects of genetic drift3,6 or model mis-specification3. In detail, the
negative f3-statistic test implemented in ADMIXTOOLS measures the correlation in allele frequency
differences between a sampled group C and two other groups A and B. A significantly negative
f3(C;A,B)—indicating that the frequencies of alleles in population C tend to be intermediate between A
and B—can only arise if population C descends from a mixture of populations related (anciently) to A
and B4. However, as the developers of the negative f3-statistic test note, “a history of admixture does
not always result in a negative f3(C; A,B)-statistic. If population C has experienced a high degree of
population-specific drift (perhaps due to founder events after admixture), it can mask the signal so that
f3(C; A,B) might not be negative”4,6. In other words, allele frequencies in population C will have drifted
enough that they will no longer tend to be intermediate between those of A and B. As Ayub et al.
showed and has been reported previously, the Kalash experienced strong drift effects – among the
highest of Eurasian populations studied to date1,3,7–9. Thus, the failure to observe a negative f3-statistic
does not provide meaningful evidence against admixture.

TREEMIX5 also does not provide evidence of admixture in the Kalash according to the analyses
reported in Ayub et al. However, this may be explained by the enormous search space necessary to
explain all potential population merges, split times and migrations among the 30 sampled populations
considered in Figure S3 of Ayub et al1 . In the original TREEMIX paper, those authors speculate that “in
graphs with complex structure ... several different histories will be compatible with the data” 5. As an
example, that paper notes how the well-documented admixture from Neanderthals into non-African
populations10 is missed when applying TREEMIX to data from Neanderthals, Denisovans, and the 53
world-wide populations of the Human Genome Diversity Panel (HGDP)5. These observations indicate that,
contrary to the claim of Ayub et al. that the ancestors of the Kalash have been isolated from the ancestors
of other extant populations for over 8,000 years, there is in fact strong evidence that they have not been
isolated over this time-frame. Hellenthal et al2 also inferred a similar signal of ancient admixture from a West Eurasian source into several populations from neighboring regions to the Kalash (the Balochi, Brahui, Makrani, Pathan, Sindhi), suggesting this introgression may be shared as part of a broader signal (though they note the Kalash event appeared to involve a more European-like source relative to the other groups). Whether or not this admixture event involved the armies of Alexander the Great is an unresolved question. One promising direction for future insight is ancient DNA analysis of skeletal remains from northern Pakistan. Further studies of this unique group11 are important, and we hope that future studies will shed light on the contributing populations.

Genetic analysis of Y-chromosome DNA (Y-DNA) by Firasat et al. (2007) on Kalash individuals found high and diverse frequencies of these Y-DNA Haplogroups: L3a (22.7%), H1* (20.5%), R1a (18.2%), G (18.2%), J2 (9.1%), R* (6.8%), R1* (2.3%), and L* (2.3%). The prevalent mtDNA Haplogroups (Quintana-Murci et al. 2004) are U4 (34%), R0 (23%), U2e (16%), and J2 (9%), which are mostly of West Eurasian origin. A study by Ayub et al. (2015) found no evidence of the claimed descent from soldiers of Alexander, which would have involved Haplogroup E1b1b common in Greece and North Africa. The study also found that they shared a significant portion of genetic drift with MA-1, a 24,000 year old Paleolithic Siberian hunter-gatherer fossil and the Yamnaya culture. The shared drift was observed between the Kalash and the Yamnaya, ancient (2,000–1,800 BCE) Neolithic pastoralists, who also shared ancestry with MA-1. Thus, the Kalash could be considered a genetically drifted ancient northern Eurasian population descended from MA-1. Moreover, recent admixture with the Yamnaya steppe herders would have introduced R1a, G and J2 to the Kalash around 4,000 years ago, while Y haplogroup R* or R1* is indigenous to the Kalash, which was inherited from MA-1 who carried the same haplogroup. The MA-1 mitochondrial genome of MA-1 belongs to haplogroup U. However, the Kalash population's mtDNA haplogroups (U4, U2e) were introduced by the Yamnaya pastoralists who carried these mtDNA haplogroups. In sum, the Kalash are an admixed population between ANE and the Yamnaya. Their ancient northern Eurasian (ANE) ancestors migrated to north Pakistan around 11,800 years ago, followed by the Yamnaya pastoralists 2,000–1,800 BCE. This admixture event would not have involved the armies of Alexander the Great.

Last Edit: Jan 25, 2019 18:18:46 GMT by Admin

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Genetic Origins of the Kalash People Jan 23, 2019 19:32:15 GMT

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Post by Admin on Jan 23, 2019 19:32:15 GMT

The Kalash represent an enigmatic isolated population of Indo-European speakers who have been living for centuries in the Hindu Kush mountain ranges of present-day Pakistan. Previous Y chromosome and mitochondrial DNA markers provided no support for their claimed Greek descent following Alexander III of Macedon's invasion of this region, and analysis of autosomal loci provided evidence of a strong genetic bottleneck. To understand their origins and demography further, we genotyped 23 unrelated Kalash samples on the Illumina HumanOmni2.5M-8 BeadChip and sequenced one male individual at high coverage on an Illumina HiSeq 2000. Comparison with published data from ancient hunter-gatherers and European farmers showed that the Kalash share genetic drift with the Paleolithic Siberian hunter-gatherers and might represent an extremely drifted ancient northern Eurasian population that also contributed to European and Near Eastern ancestry. Since the split from other South Asian populations, the Kalash have maintained a low long-term effective population size (2,319–2,603) and experienced no detectable gene flow from their geographic neighbors in Pakistan or from other extant Eurasian populations. The mean time of divergence between the Kalash and other populations currently residing in this region was estimated to be 11,800 (95% confidence interval = 10,600−12,600) years ago, and thus they represent present-day descendants of some of the earliest migrants into the Indian sub-continent from West Asia.

Figure 1
Population Structure and Isolation of the Kalash

(A) Geographic location of the three Pakistani villages where the Kalash samples were collected.

(B) Principal-component analysis (PCA) of Eurasian populations shows the first two components superimposed with the spatial kriging interpolation of the admixture coefficient of the Kalash genetic cluster. The proportion of admixture is indicated by color: orange represents the maximum level of admixture, and black represents the lowest. There is no gradient into the proportion of admixture with the Kalash cluster, suggesting a low level of gene flow between nearby populations and a high degree of isolation.

(C) Admixture analysis in which the lowest cross-validation error (k = 7) shows the unique Kalash cluster (dark green).

The Kalash Are an Ancient Genetic Isolate
PSMC analysis applied to the high-coverage Kalash, three African genomes (YRI, LWK, and MKK), and six non-African genomes showed that the Kalash, like other non-Africans, experienced a severe bottleneck 50,000–70,000 years ago. The Kalash recovered slightly after the bottleneck but never achieved an effective population size above 20,000, as observed in the GIH (the other South Asian genome) and other non-African genomes, except the MXL (Figure 2A). The Kalash have maintained a low effective size below 10,000 for more than 20,000 years before the present. This pattern of unusually small effective population size in the Kalash is also supported by the estimate from the decay of LD, which was significantly lower (p = < 2 × 10−14) than that of neighboring populations from Pakistan (Figure 2B), although the estimated absolute sizes differed between the two approaches.

Figure 2
Kalash Demographic History

(A) PSMC analysis shows a low effective population size for the Kalash.

(B) Kalash effective population size estimated from LD analysis.

(C) MSMC analysis of the time of the split between the Kalash and African genomes (YRI, LWK, and MKK) and non-African genomes from East Asia (CHB and JPT), Europe (CEU and TSI), South Asia (GIH), and America (MXL).

(D) A UPGMA (unweighted pair group method with arithmetic mean) dendrogram shows the LD-estimated time of divergence between populations. The mean time of divergence between the Kalash and other populations from the Indian sub-continent is estimated to be 11,800 years ago (dashed red line).

To examine the time of divergence between the Kalash and other genomes, we used multiple sequentially Markovian coalescent (MSMC) analysis on phased high-coverage genomes. The estimates based on pairs of genomes showed that the Kalash split first from Africans (LWK, MKK, and YRI) and then from East Asians (CHB and JPT). The split from Europeans (CEU and TSI) and South Asians (GIH) appears to have happened around the same time (Figure 2C), approximately 8,000 years ago. Examination based on LD decay in genotyping data also showed that the Kalash were the first population to split from the Central and South Asian cluster around 11,800 (95% CI = 10,600–12,600) years ago (Figure 2D). This estimate was obtained by UPGMA (unweighted pair group method with arithmetic mean) phylogenetic analysis comparing the structure of the tree in the Kalash and other South and Central Asian populations. This split time remained constant even after the addition of the YRI population. We also estimated these split times by using different subsets of non-African populations. The resulting UPGMA trees were not strongly affected by different subsets of European or South Asian populations (Figure S5), and the split times between the Kalash and other populations ranged from 9,600 to 12,600 years ago.

Last Edit: Jan 23, 2019 19:33:44 GMT by Admin

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Genetic Origins of the Kalash People Jan 24, 2019 18:45:53 GMT

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Post by Admin on Jan 24, 2019 18:45:53 GMT

The Kalash Share Genetic Drift with Paleolithic Siberian Hunter-Gatherers
We assessed the genetic relatedness between three ancient genomes and modern human populations, including the Kalash, by computing outgroup f3 statistics. The measure circumvents potential bias from classical genetic relatedness tests, such as PCA (which has sample-size bias) and FST (which is sensitive to genetic drift that has occurred since divergence of the test populations), when using ancient genomes. According to outgroup f3 statistics, the Kalash share a high level of genetic drift with MA-1, a Paleolithic Siberian hunter-gatherer skeleton dated to ∼24,000 years ago, but not a very high level with La Braña 1, the Mesolithic European hunter-gatherer (skeletal remains dated to ∼7,000 years ago) or the European farmers represented by Ötzi, the Tyrolean Iceman dated to ∼5,300 years ago (Figure 3). Similar to Native Americans, the Kalash share a high proportion of genetic drift with MA-1. In comparison with other populations from Pakistan and India, the Kalash also share a higher proportion of genetic drift with La Braña 1 and Ötzi. The level of drift shared with La Braña 1 and Ötzi is comparable to that of other North European populations (Figure 3B). We also used TreeMix to estimate the proportion of Neandertal ancestry from the high-coverage archaic Altai Neandertal who lived ∼50,000 years ago. The jackknife estimate of Neandertal-to-Kalash gene flow was 2.4% ± 0.48%.

Figure 3
Shared Genetic Drift with Ancient Genomes

(A) Proportion of shared genetic drift (measured as f3 statistics) between extant world-wide HGDP-CEPH populations (including the Kalash) and the ancient Siberian hunter-gatherer (MA-1). The magnitude of the computed f3 statistics is represented by the graded heat key. The proportion of genetic drift shared between the Kalash and MA-1 is comparable to that shared between MA-1 and the Yakut, Native Americans, and northern European populations.

(B) Ternary plot of shared genetic drift with three ancient genomes: MA-1 (left), La Braña 1 (middle), and Ötzi, the Tyrolean Iceman (right). The high proportion of genetic drift shared between the Kalash and MA-1 is comparable to that shared between MA-1 and Native Americans. In comparison with other populations from South Asia, the Kalash also share a higher proportion of genetic drift with La Braña 1 and Ötzi.

Consequences of Ancient Isolation
We also examined the effect of the inferred long-term isolation on genetic drift and natural selection in the Kalash. Our PBS analysis showed evidence of possible positive selection on 1,709 SNPs, of which 762 lie within 548 genes, including RYR2 (MIM: 180902) and ACTN3 (MIM: 102574) (Table S5). IPA showed an enrichment of selection signals in 28 genes associated with cardiovascular physiology and disease pathways (Fisher’s exact test p value = 4.61 × 10−9).

Two variants that were highly differentiated between the Kalash and the neighboring Pakistani populations stood out. One variant, rs4988235 (c.−13910C>T), which influences lactase (LCT [MIM: 603202]) expression and confers lactose tolerance, is fixed for the ancestral lactose-intolerant allele in the Kalash. The derived allele, however, is reported to be present at a moderate frequency (average 29%) in Pakistan.32 Forward-time simulations demonstrated that the observed pattern cannot easily be explained by recent genetic drift, given that only 0.1% of the 1,000 simulations achieved fixation for the ancestral allele after 500 generations (Figure 4A).

Figure 4
Consequences of Drift and Selection in the Kalash

(A) A nonsense variant in ACTN3 (rs1815739) is present at a higher frequency (left) in the Kalash than in their neighbors in Pakistan. Forward-time simulations (right) show that such a high frequency of the derived allele in the Kalash (dashed blue line) is only observed in a scenario that considers positive selection acting on the variant. The lower line represents the observed mean frequency of the derived allele in the Pakistani population, the orange lines represent the simulated allele frequency of the derived allele in each replicate in the scenario without selection, and the dark red lines represent each replicate in the scenario with positive selection. The observed frequency of the derived allele in Kalash population is reached only in the scenario with selection and only after 400 generations of drift (∼10,000 or 11,200 years ago if we assume a generation time of 25 or 28 years, respectively), suggesting that the observed pattern for this stop gain on ACTN3 can best be explained by selection acting in ancient times and not by any recent population split.

(B) The Kalash are fixed for the ancestral allele of the MCM6 intronic variant (rs4988235) that is associated with lactose intolerance. The derived allele that is associated with lactase persistence is present at moderate frequency in populations from Pakistan (left panel and upper dashed line in the right panel). Forward-time simulations (right panel) suggest that recent isolation and genetic drift cannot explain the observed pattern for this functional polymorphism in the Kalash population. Only 1/1,000 replicates (represented by orange lines) reach fixation after 500 generations of drift (∼12,500 years ago if we assume a generation time of 25 years).

The second variant, rs1815739 (c.1729C>T [p.Arg577Ter]), is a natural knockout variant in ACTN3 and has been associated with elite athletic performance.33 The derived T allele is present at a very high frequency (93%) in the Kalash. The average frequency in the remaining Pakistani populations is 47%. Using this (47%) frequency as a starting point for the forward-time simulations, we found that the very high frequency for this variant in the Kalash cannot be explained by genetic drift alone, even after 500 generations (Figure 4B). A selection signal (selection coefficient s = 0.01) achieved the observed frequency in 80% of the simulations after 500 generations. Both of these results support the long-standing isolation of the Kalash.

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Genetic Origins of the Kalash People Jan 25, 2019 18:17:39 GMT

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Post by Admin on Jan 25, 2019 18:17:39 GMT

The ancient separation of the Kalash from a common Eurasian ancestor is supported by PSMC and MSMC analyses, which estimated that the Kalash split from East Asians (CHB and JPT as proxy) prior to splitting from Europeans and other South Asian populations. The split from Europeans (CEU and TSI) and South Asians (represented here by GIH) appears to have occurred during the Neolithic period, which is also supported by the decay of LD. LD decay showed that the Kalash were the first population to split from the other Central and South Asian cluster around 11,800 (95% CI = 10,600−12,600) years ago. This estimate remained constant even after the addition of an African (YRI) population or when the Kalash were compared with different subsets of non-African populations. The pairwise times of divergence with other Pakistani populations ranged from 8,800 years ago with the Burusho to 12,200 years ago with the Hazara. Although migration and undetected admixture in reference populations could bias our estimate of the time of divergence, using different subsets of population revealed no strong bias in the split between the Kalash and South Asians, which occurred after the split between Europeans and South Asian populations.

Since this split, the Kalash have maintained a low Ne of around 2,500 (95% CI = 2,300–2,600), estimated from LD decay with no evidence of admixture. These Ne estimates are lower than those obtained from PSMC analysis because the latter method gives a single estimate of the cross-coalescence rate from the present to 24,000 years ago, whereas the linkage-based method gives us several estimates over the past 10,000 years. It is likely that PSMC analysis could not detect that the Kalash population suffered a continuous decline in effective population size. Taking into account the expected differences in Ne between autosomes and the Y chromosome, this is in agreement with the reported Ne of 237–1,124, which was estimated with observed and evolutionary mutation rates for Y chromosomal STRs.34

The Kalash represent a unique branch in the South Asian population tree and appear to be the earliest population to split from the ancestral Pakistani and Indian populations, indicating a complex scenario for population origins in the sub-continent rather than just the ancestral northern and southern Indian components identified previously.35 These Indo-European speakers were possibly the first migrants to arrive in the Indian sub-continent from northern or western Asia. This is supported by the higher level of shared genetic drift between the Kalash and the Paleolithic Siberian hunter-gatherer skeleton (MA-1) than between MA-1 and the other South Asian populations.

Whereas the Kalash have recently been reported to have European admixture, postulated to be related to Alexander’s invasion of South Asia,6 our results show no evidence of admixture. Although several oral traditions claim that the Kalash are descendants of Alexander’s soldiers, this was not supported by Y chromosomal analysis in which the Kalash had a high proportion of Y haplogroup L3a lineages, which are characterized by having the derived allele for the PK3 Y-SNP and are not found elsewhere.7 They also have predominantly western Eurasian mitochondrial lineages and no genetic affiliation with East Asians.4

We observed that the Kalash share a substantial proportion of drift with a Paleolithic ancient Siberian hunter-gatherer, who has been suggested to represent a third northern Eurasian genetic ancestry component for present-day Europeans.36,37 This is also supported by the shared drift observed between the Kalash and the Yamnaya, an ancient (2,000–1,800 BCE) Neolithic pastoralist culture that lived in the lower Volga and Don steppe lands of Russia and also shared ancestry with MA-1.36,37 Thus, the Kalash could be considered a genetically drifted ancient northern Eurasian population, and this shared ancient component was probably misattributed to recent admixture with western Europeans.

We also looked at how this long-term separation, isolation, and low effective population size affected the patterns of genetic variation in the Kalash. One striking example is the frequency of the derived allele for rs4988235, which has been linked to lactose tolerance. The Kalash, like the MA-1, are fixed for the ancestral allele for this variant, whereas their neighbors in Pakistan have been observed to have moderate frequencies of the derived allele. Although this supports their long-term isolation, it is surprising in other ways because the Kalash have no reported lactose intolerance and indeed celebrate a “milk day” during their annual spring rituals.38 This suggests that there might be additional derived lactase-persistence alleles in the LCT-MCM6 (MIM: 601806) region in this population.

Am J Hum Genet. 2015 May 7; 96(5): 775–783.

Last Edit: Sept 13, 2021 21:11:46 GMT by Admin