Y-Chromosome and mtDNA Genetics Reveal Significant Contrasts in Affinities of Modern Middle Eastern

**~~Kamal900~~** · 04-01-2015, 04:46 PM

Y-Chromosome and mtDNA Genetics Reveal Significant Contrasts in Affinities of Modern Middle Eastern Populations with European and African Populations

PLoS One. 2013; 8(1): e54616. Published online 2013 Jan 30.

The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations.

In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of FST's, RST's, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa.

Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations.

Results

Phylogeographic distribution of mtDNA haplogroups

A total of 185 distinct HVS-I SNPs were identified across all populations (Table S5). The distribution of mtDNA haplogroups shows systematic variation with geography.

The haplogroups' geographical distribution shows affinity between the Northern Levant (modern day Lebanon and Syria) and Europe with clear distinctions between the Levant and the Arabian Peninsula with regards to Africa (Fig. 1, Table 1). The main mtDNA haplogroups for both Europe and the Northern Levant are H and R*. The subhaplogroup H is more frequent in Europe (45%) than in the Levant (25%). Among the Levantine populations, only the Lebanese share Western Europe's overrepresentation of H.

Fisher exact tests were applied to determine when haplogroup frequency differences among populations over both Pan-Mediterranean tests (Table S6), and regional Middle Eastern tests (Table S7), were significant. They reveal patterns of significant over- and under- representation of haplogroups marking regional affinities.

In Lebanese, haplogroups H, HV, T, and K are over-represented, while Syrians are overrepresented in haplogroups T and K. Western Europeans show overrepresentation of haplogroups H, K.

By contrast, haplogroups J, R0, and M are significantly overrepresented in Saudis, and underrepresented in Western Europeans. Haplogroup J was also significantly overrepresented in Iraqis, among Palestinians, and Yemenis.

The African haplogroups L* and L3* are very rare (frequencies less than 1%) and underrepresented in Europe, noting that rarity reduces the power of these tests. In the Levant, Lebanese have the lowest frequency for these haplogroups with generally highly significant underrepresentation, The L haplogroups show rather broad penetration into Yemen, with most being significantly overrepresented, with Yemenis being the only population with an overrepresentation of L6. We have not found haplogroup L6 in our Lebanese (N = 980), Syrian (N = 234), and Jordanian samples (N = 290).

Some U subhaplogroups show regional localization, but none of them rose to sufficient frequency to make any significant contribution to the PCA. U3 appears most frequently in Jordan (Fisher's test: p = 2.39e-8), with representation throughout the Middle East. U4 (p = 1.49e-7) and U5 (p = 2.2e-16) appear to be more heavily European.

The two leading principal components displayed in Figure 2 capture 47.9% and 26.9% of the variance showing a well-defined separation between Mediterranean African populations and sub-Saharan populations (Fig 2a). There is a clear cluster of North African populations comprised of Libyans, Moroccans, and Tunisians. The Nile River marks another boundary of mtDNA differentiation within Africa, linking Egypt, Ethiopia and Kenya but also extending through to Yemen. Yemenis and Saudis both associate strongly with Egyptians, whereas the Jordanian, Lebanese, Palestinian, and Syrian populations clustered together. Thus, the Arabian Peninsula population clusters were relatively differentiated from the more northern Levantine populations.

The dendrogram based on mtDNA haplogroup frequencies (Fig 2b) reveals the strongest differentiation across the Sahara, showing the northern populations differentiated from the southern ones (with Nigeria, Kenya, Mali, Libyan South Sahara, and Burkina-Faso). Egyptian, Yemeni, Saudi Arabian, and Ethiopian populations form a cluster that is distinct from the rest of North Africa, the remaining parts of the Middle East, and Europe. Among these, Libyans, Moroccans, and Tunisians, form a cluster.

UPGMA and PCA showed Yemenis and Saudis (two of the STR predicted Hg populations) closely associated, forming a clear outlier to clusters identifying more northerly Middle Eastern populations and Europe. Slovaks (the third predicted population) also formed a distinct outlier to all of these. Africans were partitioned into northern African populations and Sahel populations, and distinct from the other populations. Burkinabe formed a very distinct outlier to every other population.

For the mtDNA HVS-I FST MDS analysis, the European populations formed a clear cluster very close to the Cypriots, Jordanians, Lebanese, Palestinians, and Syrians. Egyptian, Libyan, Moroccan, and Tunisian populations form a clear cluster. Significantly, Yemenis are on the far side of North Africans, distinct from the Levantine populations and the Libyan Sahara population stands significantly separated from the North African group. The sub-Saharan populations are clearly distinguished from the Mediterranean populations and show significant distances between them in comparison to the Mediterranean populations. The mtDNA HVS-I MDS and dendrogram show most of the Levantine and Arabian Peninsula populations clustering together. Significantly, Yemenis do not seem to cluster with proximal African populations or with Saudis. The entire Levant population seems to cluster with Western Europeans, Southeastern Europeans, and Slovaks.

In contrast to mtDNA, the Y-STR-based MDS shows a tight cluster of Cypriots, Egyptians, Jordanians, Lebanese, Palestinians, Saudis, Syrians, and Yemenis, though Libyans, Tunisians, and Moroccans extend away from this cluster. The Southeastern Europeans, Slovaks, and Western Europeans lie in the opposite direction. The dendrogram shows a European cluster closer to the Levant/Arabian Peninsula cluster and the North African cluster acting as out-group to those.

In general, the MDS plots for mtDNA and Y-STRs show general agreement of European populations extending from the Levant in one direction and North Africans tending to extend in another direction. This places the Levant as a middle ground, either by averaging of in-migration, as a source feeding both North African populations and European populations, or both. The Y and mtDNA MDS plots differ in identifying affinities of Lebanese with Europeans and Yemenis with Egyptians.

Comparative analyses of paternal and maternal lineages in the Levant

The relative distance heatmap plot (Figure 4) shows proportion of genetic distances of mtDNA vs. Y. Red colors indicate greater distance of mtDNA vs. Y, while blue colors indicate greater distance of Y vs. mtDNA. Hierarchical clustering organizes the plot relating populations showing similar profiles of Y vs. mtDNA isolation. Most striking is that Saudis, Kenyans, and Yemenis cluster together away from Lebanese, Syrians, Palestinians, Cypriots and Jordanians in terms of showing relatively high differentiation of mtDNA vs. Y-chromosome genetics.

In order to preserve normalization, common subsets comprised of the 11 populations in common in both dendrograms were included. Each of the candidate partitions marking mtDNA affinities and Y affinities formed three groups. The groups representing mtDNA affinities were: (1) Southeastern Europeans, Lebanese, Slovaks, and Western Europeans vs. (2) Cypriots, Jordanians, Palestinians, Saudis, and Syrians, vs. (3) Egyptians and Yemenis. The groups representing Y affinities were: (1) Southeast Europeans, Slovaks, and Western Europeans vs. (2) Cypriots, Lebanese, Syrians, and Yemenis, vs. (3) Egyptians, Jordanians, Palestinians, and Saudis.

These two affinity groupings were applied to both the Y and the mtDNA data, yielding results presented in Table 2. Both Y and mtDNA tend to cluster African, European, and Middle Eastern populations separately, and all combinations showed highly significant between-group vs. within-group variations. This reflects the dominating clustering distinguishing Africa, Europe, and the Middle East populations that mean-linkage clustering is picking up.

Discussion

Here we present mitochondrial characteristics of a large group of newly typed samples from five populations (Lebanese, Libyans, Jordanians, Palestinians, and Syrians) and compare their geographical affinity, distribution, and frequency with those of Y-chromosome markers from populations across the broader region of Africa, Europe and the Arabian Peninsula.

The Y-chromosome results of the current study are in agreement with previous studies, suggesting a Middle Eastern gene pool with greater affinity to Africa. Maternal lineages of the Levantine populations studied here, however, reveal stronger European genetic affinities, while not showing Arabian peninsular influences.

The contrast between the two lineages

Our results show a contrast of mtDNA affinities with previous Y-DNA results [25]. While our Y-DNA MDS and mean-linkage clustering showed a much greater proportion of East African and Near East Y-chromosomes in the Levant, evidence of much less mtDNA affinity, however, was found between the Levant and its southern neighbours.

European mtDNA affinity with the Levant was established in haplogroup frequency data through Fisher exact tests, PCA, and mean-linkage clustering based on Euclidean distances, and in HVS-I derived FST distances via MDS and mean-linkage cluster analysis. The mtDNA results are distinct from the Y-STR RST-based mean-linkage cluster analysis that showed closer affinity of the Levant populations with Cypriots, North Africans, and Yemenis, than to Europeans.

This cluster analysis suggests that the position of Lebanese relative to European Y-chromosome genetics represented in STR haplotype data is also much more ambiguous than suggested entirely by frequency analysis, revealing otherwise cryptic relationships between Lebanese's Y-STR structure and that of Europeans. Cluster analysis of Y-chromosome frequency based data shows similar partitioning of Europe, Africa, and Middle East, with the Levant much more strongly associated with the Middle East than Europe. As with mtDNA, African Y-chromosome haplogroup data also shows a clear partition between Northern populations and Sahel populations. Due to uncertainties in haplogroup inference from STRs, affinities of Yemenis with Ethiopians vs. Egyptians are uncertain, as are the relationships of Saudi Arabian haplogroups both similar to Yemenis or differentiated from Yemenis in affinity with African populations.

Arabian genetic expansions: Arabia East Africa, and North Africa

From the 7th millennium B.C.E., empire expansions and trade, including the slave trade, heavily influenced genetic migration between Yemen and East Africa. Alternatively, known trade networks linking Egypt with Yemen included those for obsidian, and later through Aksum, spices, incense and other precious materials, as well as slaves [76]–[78]. It is particularly clear from prior mtDNA studies of this region that East African migration into Arab populations involved females to an extensive degree [79]. While Ethiopian and other East African populations may appear to be better candidates for the origins of modern Yemeni populations, our PCA and MDS analyses, and their associated mean-linkage clustering of Yemen's mtDNA, show greater affinity between Yemenis, Egyptians and North Africans. They share in common haplogroups J, L0, L2, and N1. Comparison of mtDNA HVS-I FST distances also suggest that Yemen appears more similar to Egypt than Ethiopia.

It is likely the pattern of Hg J's significant penetration, and the shared underrepresentation of Hg H, tips the balance for Yemenis' mtDNA affinity with Egyptians. Given the significant underrepresentation of Hg J in East Africa, while not being significantly uncommon in Egypt, it is therefore plausible that Arabian female gene flow followed well established trade routes on the Red Sea with Egypt and North Africa while avoiding assimilation of Yemeni L6's on the way.

The most striking feature of the heat map (Fig 4) is the relative isolation of mtDNA genetics of Yemenis and Saudis from the other populations in the Middle East in comparison to Y-chromosome variation. While Yemenis appear to share overrepresented haplogroups that characterize each of its neighbouring populations, none of the African populations have become dominated by Saudi Arabian J's, nor have Middle Eastern populations been differentially dominated by the in-migration of African L's the way Yemenis have.

Whether considering haplogroup composition revealed in Fisher tests, PCA, or FST based MDS analysis of HVS-I data, mtDNA shows a much stronger affinity between Levantine populations and Europeans compared with the rest of the Middle Eastern populations, or with North Africans. While Lebanese and Yemeni mtDNA epitomize very distinct affinities to different populations and regions well outside of the Middle East, Saudi Arabia seems to display strong local over-representation haplogroup J, while Yemen is even more localized in its L6. Further, these large-scale differences in affinity between mtDNA genetics appear in sharp contrast to regional affinities seen in their Y-chromosomal counterparts. While the mtDNA signal is sharp and clear in its affinities, the Y-chromosome results show somewhat more ambiguous associations in RST based analyses, with Lebanese showing less within-group variation when organized consistently with mtDNA and demonstrating associations closer to Europeans than Africans. This would suggest that while male migrants accompanied female migrants, especially to Europe, females did not always accompany male migrants, especially into North Africa. This leaves a more ambiguous signal for male compared to female migrations.

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