The present study aims to shed light on the population history of the Israeli Druze and assess the findings in light of three hypotheses advocating Arabian, Iranian-Iraqi or Near Eastern roots (Table 1) while examining claims that the Druze are a ‘genetic isolate’. Considering the Druze admixture components, biogeographical affinity, paternal and maternal haplogroups and genetic similarity to neighbouring populations allows us to tentatively reconstruct their history and explain some of their habitual preferences.

Evaluating the evidence for the biogeographical affinity of Druze

Although predicted in part to Syria (Fig. 3[A1]), like Palestinians, Lebanese and Syrians (Fig. 3[B–D]), only a minority of the Druze (Fig. 3[A2]) could be considered to be highly localised to the Levantine. The mixed population structure of the Druze has two biogeographical affinities: a southeast Turkish-northern Iraqi one overlapping the Zagros Mountains and close to Mount Ararat and a southeast Syrian one, close to Mount Hauran. Though the Turkish affinity of the Druze can be observed for a smaller fraction of Druze, likely due to on-going gene exchange with Syrians (Fig. 3[A1]), it can still be recognised as the primary affinity of nearly 80% of Druze (Fig. 3[A2]), suggesting its antiquity compared to the Syrian affinity. Such a conclusion is in agreement with our ancient DNA analysis since, in relation to ancient individuals (12,000–1000 B.C.), a third of the Druze appear like ancient Armenians, whereas the remaining exhibit nearly 80% ancient Armenian ancestry compared to less than 15% ancient Levantine ancestry (Fig. 5). Altogether these findings suggest that the proto-Druze were from tribes who resided around the Zagros and surrounding mountains and Syrian tribes with whom they exchanged genes (Fig. 3[A1]) subsequent to, and after, their migration to Palestine. We speculate that the gene exchange events with non-Druze were uneven across the population, which helped retain some of the Near Eastern admixture signature that distinguishes Druze from other Levantine populations (Figs 3[A2–E2] and 5). Consequently, the majority of Druze are genetically closer to Syrians than to other Levantine populations (Fig. 4) and share a genetic similarity with Arabians as well as Near Eastern populations (Figure S2). These results are in agreement with those of Elhaik21, reporting Southern Turkish and Northern Syrian biogeographical affinities in support of the Near Eastern hypothesis for the emergence of Druze over alternative hypotheses that fail to explain the mixed biogeographical affinities of the Druze (Figs 3 and 4).

Evaluating the evidence for the biogeographical affinity of non-Druze Levantine populations

The biogeographical affinities of the Druze are unique compared with neighbouring Levantine populations. Only a minute fraction of Lebanese and Syrians share a Turkish affinity (Fig. 3), and both Syrians and Palestinians are highly localised to the Levant. While these results do not rule out a partial Turkish ancestry for some of the Syrians, they suggest that any genetic evidence for such an ancestry has decayed over time due to on-going gene exchange with Levantine populations and the absence of large inflows of migrants with relatively distinct population structure. The biogeographical affinity of Palestinians concurs with previous studies employing uniparental markers33 and historical records, which suggest that they descended, at least in part, from local Israelite inhabitants who converted to Islam following the Muslim conquest in the early 7th century6,34.

Fascinatingly, most Lebanese individuals were predicted along the northwestern Incense Route leading from southern Arabia to the Mediterranean, used by merchants between the 4th century B.C. and the 2nd century A.D. This multi-origin of the Lebanese (Fig. 3[C1]) may be explained either by the 7th century Arabian expansion, which saw a large scale movement of Arabian tribes from the Arabian Peninsula into the Middle East, or by the northern expansion of nomadic Bedouin tribes known as the Nabataeans. By the end of the fourth century the Nabataeans had established an empire which occupied Northern Arabia and the Southern Levant for four hundred years, making migration into Lebanon at this time highly probable35. However, as both Nabatean and late Arab conquerors inhabited the same geographical regions and emerged around similar historical periods, they likely share the same genetic background. Therefore, the exact ancestry of Lebanese cannot be properly deciphered without ancient DNA from the potential ancestral populations, currently unavailable.

Reconstruction of Druze population history

When combined with historical and anthropological records, our findings allow a cautious reconstruction of certain aspects of Druze population history. First recorded as “mountain dwellers” as early as the 12th century A.D.4, the Druze exhibit a consistent propensity for residing in the highest mountains whether in Israel (Mounts Hermon and Carmel), Syria (Mount Hauran) or Lebanon (Mounts Lebanon and Shuf)5. These mountains provide the Druze with protection and allow them to maintain the close societal structure that is integral to their religious practices. This critical aspect of Druze life has been neglected by many previous studies on the origin of Druze. Our GPS analyses localised most Druze to the highest and largest mountainous Regions of southeast Turkey and northern Iraq and the remaining individuals close to the Syrian Mount Hauran, where most Druze reside today. Our analyses also indicated an on-going mixture between these two groups. These findings hint at a tantalizing possibility that, over time, at least some of the proto-Druze may have developed a genetic adaptation to high altitudes, such as has been reported in several other mountainous populations36. Our findings are in agreement with the results obtained by fineSTRUCTURE where populations were clustered into clades based on their population structure similarity27. Druze were clustered into the “West Asian” clade together with Adygei, Armenian, Cypriot, Georgian, Iranian, Lezgin and Turkish populations. Such findings are also in agreement with a recent ancient DNA study28, where Druze exhibited genetic similarity to Chalcolithic and Bronze Age Armenians and a Chalcolithic Anatolian. In that study, Druze clustered remotely from all Bronze Age and Neolithic Levantines, whereas Palestinians, Bedouins, Syrians and a few Lebanese clustered with Levantine populations.

The most parsimonious explanation for our findings is that some of the proto-Druze emerged from Armenian-Turkish tribes residing in the Zagros and surrounding mountains, prior to the end of the first millennium A.D. (Figs 3[A1,A2] and 5). It is unclear when these tribes migrated to the Levant, as there have been several small migrations of Turkish people into the region throughout the Middle Ages, and only some of these have left a detectable DNA hallmark27. However, the most significant Turkish migration was the expansion of the Seljuk Turkish Empire into the region in the years following the Battle of Manzikert, north of Lake Van (1071 A.D.). By 1079 A.D., the Seljuqs had reached Syria and Palestine and settled in Iran, Anatolia and Syria37. The Druze were first recorded in that region ~150 years later4. It is therefore possible that the proto-Druze population was part of this early Seljuk expansion. This explanation is supported by the short genetic distances found between the Druze and several Near Eastern populations reported here (Figure S2) and elsewhere12 and ancient DNA evidence indicating that this similarity has roots in the Chalcolithic and Bronze Age28. During their residence in Syria, and prior to or during, their admission into Druzism, these migratory tribes have probably experienced uneven gene exchanges with Syrians and Lebanese or Arabian tribes dwelling along the Incense route (Fig. 3[A1]), which increased their genetic diversity. Yet we venture that they retained some of their habitual preferences and continued residing in mountains.

Such a scenario, however, may be at odds with accounts of the official closing of the religion to new adherents in 1043 A.D., thirty years prior to the Seljuk expansion38. To resolve this contradiction, we speculate that the sealing of Druzism did not necessarily mark the de facto sealing of the faith, nor its closure to Middle Eastern proselytes. Although not actively encouraged by religious authorities, old and modern historical records, along with our genetic findings suggest that it is very likely that some conversions to the Druze faith were allowed after the 11th century A.D. For example, Betts8 alludes to several notable instances over the past millennium where non-Druze have been admitted into the religion; such as the Jumblatt family, one of the leading Druze political clans of Lebanon. Furthermore, our dating analysis suggests that the major gene exchanges that shaped the Druze genome continued at least until the early 12th century A.D. Since other Levantine populations who do not live in seclusion have similar admixture dates, the admixture date cannot be interpreted as evidence that gene exchanges with neighbouring populations stopped, but rather that no population-wide admixture event with a population that is genetically relatively dissimilar to Levantine populations had occurred27.

By the 10th century A.D., the Fatimid dynasty ruled Syria, Lebanon, Palestine, Jordan, Egypt and North Africa, which afforded Al-Hakim, the sixth Fatimid caliph and one of the founders of Druzism, the opportunity to spread his ideas throughout the Middle East. Adherents could have developed their own division of Druzism that incorporated both the original beliefs of Cairo Druze and other early monotheistic religious and philosophical ideas with those which they were previously familiar, including those that may have allowed conversions. Indeed, the Druze religion incorporates eclectic fundamental religious ideas from throughout the Middle East5, and the Druze themselves proclaim a diverse descent from Yemenite, Tanukh, Kurdish and Iranian tribes4,35. Such a heterogeneous Middle Eastern descent is supported by their high haplogroup diversity compared to neighbouring populations (Fig. 3[A1–E1]).

It is therefore not unreasonable to consider that Druze proselytization in Middle Eastern communities endured after the oppression of the Cairo sect. Conversion efforts may have continued on a small scale until such regional operations drew the unwanted attention of local governments, forcing Druze leaders to halt further conversion efforts5.

The matter of gene exchange between Druze and non-Druze should be addressed with caution, as marriage to a non-Druze can lead to ostracism from the community39 and is still considered a fundamental characteristic of Druze identity40 in the Middle East and the diaspora1. In 2002, a survey of the Israeli Central Bureau of Statistics reported that the proportion of atheists among Israeli Druze is the highest of all Israelis (48%), including Jews (44%), Arabs (18%), Muslims (12%), and Christian Arabs (35%)41. An independent study examined the 145 officially recorded cases of Israeli Druze ‘straying’ from the religion, often motivated in part by a desire to marry outside the community39. Despite the excommunication fears, there has been a growing practice of exogamous marriages amongst Druze, particularly in the United States42 where inter-religious marriages, especially between Druze men and non-Druze women, are becoming more commonplace. These are becoming increasingly widespread in Israel43. However, such practices are expected to change according to the regional marriage laws that may be very strict. For example, in Lebanon, civil marriages are not allowed44, whereas in the US fewer prohibitions on marriage exist. With a lack of updated information regarding Druze marital practices, it is reasonable to conclude that the practice of exogamy is on the rise among the Druze, although it is difficult to assess whether this also entails a decline in the number of “religious” Druze due to the changing nature of this term. Secularisation processes, including the decline of strict religious practices such as endogamy5, especially among the younger generation40, can be expected to intensify the gene exchanges with neighbouring populations over time. For instance, our admixture analysis (Fig. 4) singled out a Druze individual whose admixture signature closely resembles a Palestinian one, probably due to a very recent gene exchange event. Though it may appear insignificant, we note that this individual was found in the HDGP cohort, carefully curated and then analysed thousands of times.

Misconception of genetic isolates

Evaluating whether Druze are a ‘genetic isolate’ necessitates an understanding of this concept. An ideal genetically isolated population is an endogamous group dating back to ancient times that derived from a small number of individuals who became isolated after a founding event. Such communities would be characterised by minimal mixing and reduced gene flow with neighbouring populations or their potential progenitors, facilitated by strict societal practices, effective geographical barriers or both45. Following Cann’s definition, isolated populations are expected to exhibit a small effective population size (Ne) in the range of 10–100 individuals (<80 for the New World founding population)46,47, highly homogeneous genomes in terms of allele frequencies, high inbreeding coefficients and longer runs of homozygosity compared with panmictic populations32. Sufficiently long isolation, which has persisted for hundreds of generations, may also generate novel combinations of alleles that could contribute towards otherwise rare genetic disorders becoming more prevalent in the isolated population46. A conclusion of genetic isolation can therefore be reached only after extensive genetic comparisons of the putative isolated population with its neighbouring populations and potential progenitors and after excluding artefacts that may lead to such an impression, like small sample sizes, studying insufficient numbers of markers and questionable study designs.

In reality, we estimate that less than 20% of the worldwide populations (estimated at 6,000 populations48) have been fully genetically tested, which raises concerns about whether claims of genetic isolation have been sufficiently substantiated. Moreover, in practice, most human populations living inland are not ideal ‘population isolates’ since they have never lived in true isolation nor seclusion. Studies of the apportionment of human genetic variation have long established that most human variation is within population groups and that the additional variation between population groups is small but greatest when comparing different continental populations49. The number of actual genetic isolates or even relative isolates is therefore likely to be far lower than the number of populations professed to be so (e.g.50,51).

Some authors have considered the Druze to be a ‘population isolate’ and a ‘genetic refugium’ based on little or dubious genetic evidence, which fails to meet the above criteria. For example, Shlush et al.12 stated that the “social structure has turned the Druze into transnational isolates – a population which remains genetically isolated largely through the social practice of endogamy and consanguinity.” The authors also argued that the relatively high frequency of mtDNA X, H and K haplogroups are indicative of isolation (“the refugium hypothesis based on mtDNA haplogroup X analysis was corroborated by the finding of high diversity for the Druze mtDNA haplogroups H and K, with the added finding of novel lineages not shared with nearby populations.”). However, we found that both H and K maternal haplogroups show similar frequencies in Druze and Lebanese (Table S5) and that the X haplogroup variation occurs largely between villages12,52, which could be a product of genetic drift. Likewise, the lack of paternal haplogroup K in neighbouring populations was misinterpreted as evidence of isolation (“The finding of the enrichment of the [non-recombining Y] NRY haplogroup K among the Galilee Druze with no detection in samples from other subregions, further supports the relative isolation of this region, even among the Druze”), although it is also found among Palestinians (4.6%), Syrians (3.2%) and Lebanese (0.3%) (Table S4). Since variation in haplogroup frequencies is typical between and within human groups, variation in haplogroups alone cannot be taken as an incontestable indicator of genetic isolation. Higher rates of endogamy among Druze are likely to increase the frequency of certain haplogroups through genetic drift.

Zidan et al.15 have studied Israeli Druze that trace all four grandparents to the same communities in Syria and Lebanon. The authors argued that the Druze are a ‘population isolate’ based on two analyses. First, a PC analysis portrayed Druze as clustered separately from “any other population” enveloped by genetic nothingness and immersed in a genetic vacuum. This statement is peculiar since not only were several populations for which genetic data were available not tested, but some of the populations included in latter analyses were excluded from this analysis, critically Lebanese, who, like Eurasian Jews, have been repeatedly shown to cluster with the Druze in other PC analyses17,21,53,54. Second, an identical-by-descent (IBD) analysis yielded no shared segments between Druze and non-Druze. However, the IBD segments used for that analysis were 3 cM, 15 times higher than the recommended threshold55. Had the authors applied a more reasonable threshold of 1 cM, as shown in Fig. 6, they would have likely obtained a much higher IBD sharing between the Lebanese Druze and Lebanese non-Druze, as can be expected from the Lebanese origins of the Druze included in their cohort.

Figure 6 Proportion of total IBD sharing between Druze and different populations. The maximal IBD between each Druze and an individual from each population are summarised in box plots. Lines pass through the mean values. Full size image

Not only does the genetic isolation theory remain unsupported by prior genetic studies but strong genetic evidence exists to the contrary. The Druze inbreeding coefficient and runs of homozygosity are typical of Levantine populations, like Palestinians and Bedouins16,56, none of which have ever been considered a ‘population isolate’ on these grounds. Levantine populations showed higher inbreeding coefficients and longer runs of homozygosity compared to Africans and Europeans, but lower compared to Central Asian and American populations. These results are to be expected given the high level of consanguinity among Druze (47%), Muslim Arabs (41.7%) and Bedouins (60.1%)57. The Druze’s effective population size (5,700 ± 300) is much higher than would be expected for a population isolate and is within the same order of magnitude as Palestinians (7,000 ± 300) and Bedouins (6,500 ± 300)58.

Our results further challenge isolation perceptions on several grounds: first, the Druze admixture signature is very similar to that of neighbouring Levantine populations (Figs 1 and 4 27), indicating the existence of gene flow between them. Second, the genetic distances within Druze are at the low 20th percentile (Figure S1), and none of the populations exhibiting shorter distances have been denoted a “genetic isolate”. Third, the Druze exhibit high genetic diversity (as evident from their GPS results) (Fig. 3[A1]), whereas a population isolate would be expected to be highly clustered and genetically homogenous. We have shown that the Near Eastern genetic signature of the Druze decays (Figs 1 and 3[A1,A2]) likely due to gene exchange with other Levantine populations. Finally, the Druze have a largely similar haplogroup diversity to other Levantine populations (Fig. 3).

Stereotyping populations as ‘genetic isolates’ has been criticised by geneticists and non-geneticists alike. Lipphardt50 demonstrated that biologists and geneticists use historical, social and administrative data to promote the notion of population isolates. While true genetic isolates are very useful in studying evolutionary, genetic and past demographic processes, their misidentification can have harmful consequences that could actively push a population towards isolation due to the stigma and discrimination such a label could entail. An extreme example of the detrimental impact of divisive research on vulnerable populations is documented in Kyllingstad’s59 study on the research conducted on the Scandinavian Sami people. Throughout the mid- to late-19th century scientists used a range of problematic methods to argue that the Sami people were isolated from the Norwegian minority, often noting their purportedly distinct genetic ancestry. This assumption had many negative consequences for the Sami people, impacting on their territorial and political rights while contributing to the justification of wide-spread and systematic discrimination at the hands of governments. It is fundamental that any attempt at classifying a population, such as the Druze, as ‘genetic isolates’ is approached with caution and is founded on irrefutable genetic evidence as well as historical, sociological and administrative data.

Limitations

Our study has several limitations. First, the modest sample size of the Israeli Druze may have obscured a more complex population structure that exists within and between Israeli and non-Israeli Druze communities, as noted by12. Second, because GPS uses the average of all an individual’s ancestors to infer geographic origin the results could reflect either the actual origin or a mid-point of many origins. We emphasise that the biogeographical analysis that relies on deriving inferences from the geographical locations of modern-day populations10 is inherently limited to the time these populations obtained their concurrent population structure, which may be as old as several centuries in the Middle East (see ref. 25 on how to interpret the results of biogeographical tools). This limitation presents difficulties when inferring the population history of the Druze and requires confirmation using ancient DNA from the relevant time periods. While the ancient DNA findings are in general agreement with our results (e.g., Fig. 5 and ref. 28), the ancient individuals predate the known emergence of the Druze. Therefore, further validation using ancient individuals from the first millennium is necessary to confirm our conclusions. Finally, in the absence of religious information about the Syrian and Lebanese individuals of this study we cannot exclude the possibility that they may include Druze individuals and introduce a certain bias into our interpretations.