Genetic heterogeneity of Berber peoples as a result of differential migration and admixture patterns

Trabajo presentado en la Annual Meeting of the Society for Molecular Biology and Evolution (SMBE 2015), celebrada en Viena del 12 al 16 de julio de 2015.The genome-wide structure of North African populations has been describe d as an amalgam of autochthonous, Middle Eastern, European and Sub-Saharan ancestries. The indigenous North African genetic ancestry has been estimated to be derived from a "back to Africa" migration dated in pre-Holocean times, and suggested to be in high est frequency in Berber populations, which are considered the autochthonous populations of North Africa.The lack of genetic knowledge on Berber populations in the current datasets prevents the understanding of the complex population processes occurred in North Africa. We have genotyped ~900,000 genome-wide SNPs in four different Berber groups and compared the results with other North African and neighboring groups. Our research reflects the complex structure of North African populations due to multiple admixture processes. Berber groups are very heterogeneous, showing different patterns of admixture and demographic histories, such as relevant endogamy levels within groups. The analysis of haplotype structure and the ancestral relationship between individuals has allowed us to estimate historical dates for some migrations coming from the Middle East and Sub-Saharan Africa into North Africa, affecting in an heterogeneous way the populations of the region. In addition, the comparison of autosomal and sexual chromosomes has shown a sexual bias in the admixture between North African populations and their surrounding neighbors, being the North African autochthonous component mainly derived from males and the European admixture driven by women. This study brings light to the origin of Berbers and the complex admixture processes in the population of North Africa.N

Heterogeneity in palaeolithic population continuity and neolithic expansion in North Africa

North Africa is located at the crossroads of the Mediterranean Sea, the Middle East, and the Sahara Desert. Extensive migrations and gene flow in the region have shaped many different cultures and ancestral genetic components through time [1–6]. DNA data from ancient Moroccan sites [7, 8] has recently shed some light to the population continuity-versus-replacement debate, i.e., the question of whether current North African populations descend from Palaeolithic groups or, on the contrary, subsequent migrations swept away all pre-existing genetic signal in the region. In the present study, we analyze 21 complete North African genomes and compare them with extant and ancient genome data in order to address the demographic continuity-versus-replacement debate, to assess whether these demographic events were homogeneous (including Berber and Arabic-speaking groups), and to explore the effect of Neolithization and posterior migration waves. The North African genetic pool is defined as a melting pot of genetic components, including an endemic North African Epipalaeolithic component at low frequency that forms a declining gradient from Western to Eastern North Africa. This scenario is consistent with Neolithization having shaped most of the current genetic variation in the region when compared to posterior back-to-North-Africa migration waves such as the Arabization. A common and distinct genetic history of the region is shown, with internal different proportions of genetic components owing to differential admixture with surrounding groups as well as to genetic drift due to isolation and endogamy in certain populations.Serra-Vidal et al. report that human North African genomes exhibit traces of continuity from Paleolithic times in a decreasing pattern from West to East. Neolithic and posterior migrations did not erase the pre-existing Paleolithic substrate. The demographic impact of Neolithization was larger than posterior migrations, such as Arabization.This work was supported by the Spanish Agencia Estatal de Investigación (MINEICO, AEI) and Fondo Europeo de Desarollo Regional (FEDER) grants CGL-2013-44351-P and CGL2016-75389-P, the “Unidad de Excelencia Maria de Maeztu” MDM2014-0370, and Agència de Gestió d’Ajuts Universitaris i de la Recerca (grant 2014SGR866). G.S.V. was supported by an FI (2017FI_B2 00010) scholarship awarded by the Generalitat de Catalunya

The impact of recent demography on functional genetic variation in north african human groups

The strategic location of North Africa has made the region the core of a wide range of human demographic events, including migrations, bottlenecks, and admixture processes. This has led to a complex and heterogeneous genetic and cultural landscape, which remains poorly studied compared to other world regions. Whole-exome sequencing is particularly relevant to determine the effects of these demographic events on current-day North Africans' genomes, since it allows to focus on those parts of the genome that are more likely to have direct biomedical consequences. Whole-exome sequencing can also be used to assess the effect of recent demography in functional genetic variation and the efficacy of natural selection, a long-lasting debate. In the present work, we use newly generated whole-exome sequencing and genome-wide array genotypes to investigate the effect of demography in functional variation in 7 North African populations, considering both cultural and demographic differences and with a special focus on Amazigh (plur. Imazighen) groups. We detect genetic differences among populations related to their degree of isolation and the presence of bottlenecks in their recent history. We find differences in the functional part of the genome that suggest a relaxation of purifying selection in the more isolated groups, allowing for an increase of putatively damaging variation. Our results also show a shift in mutational load coinciding with major demographic events in the region and reveal differences within and between cultural and geographic groups.This work was supported by the Spanish Ministry of Science and Innovation (grant numbers I-COOP0018, PID2019-106485GB-I00, and PID2022-138755NB-I00) and “Unidad María de Maeztu” (CEX2018-000792-M) funded by the MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”

mtDNA Analyses of Molecular Variance (AMOVA) in the Algerian samples.

<p>*** P<0.0001; ns: not significant</p><p>North = Algiers, Oran (both)</p><p>South = Mozabite, Reguibate, Zenata</p><p>Arabs = Reguibate, Algiers, Oran1, Oran2</p><p>Berbers = Zenata, Mozabite</p><p>^# Arabs without the Reguibate</p><p>mtDNA Analyses of Molecular Variance (AMOVA) in the Algerian samples.</p

Y chromosome Analyses of Molecular Variance (AMOVA) in the Algerian samples.

<p>*** P<0.0001</p><p>* P<0.05; ns: not significant</p><p>North = Algiers, Oran, Tizi Ouzou</p><p>South = Mozabite, Reguibate, Zenata</p><p>Arabs = Reguibate, Algiers, Oran</p><p>Berbers = Zenata, Mozabite, Tizi Ouzou</p><p>^# Arabs without the Reguibate</p><p>Y chromosome Analyses of Molecular Variance (AMOVA) in the Algerian samples.</p

Genetic heterogeneity in Algerian human populations

The demographic history of human populations in North Africa has been characterized by complex processes of admixture and isolation that have modeled its current gene pool. Diverse genetic ancestral components with different origins (autochthonous, European, Middle Eastern, and sub-Saharan) and genetic heterogeneity in the region have been described. In this complex genetic landscape, Algeria, the largest country in Africa, has been poorly covered, with most of the studies using a single Algerian sample. In order to evaluate the genetic heterogeneity of Algeria, Y-chromosome, mtDNA and autosomal genome-wide makers have been analyzed in several Berber- and Arab-speaking groups. Our results show that the genetic heterogeneity found in Algeria is not correlated with geography or linguistics, challenging the idea of Berber groups being genetically isolated and Arab groups open to gene flow. In addition, we have found that external sources of gene flow into North Africa have been carried more often by females than males, while the North African autochthonous component is more frequent in paternally transmitted genome regions. Our results highlight the different demographic history revealed by different markers and urge to be cautious when deriving general conclusions from partial genomic information or from single samples as representatives of the total population of a region.This study was supported by the Ministerio de Economía y Competitividad grant CGL2013-44351-P and by Direcció General de Recerca, Generalitat de Catalunya grant 2014SGR866

Correlation plots of the ancestry proportions at k = 4 in the ADMIXTURE analysis comparing autosomes and X-chromosome SNPs.

<p>North African, sub-Saharan, Middle Eastern, and European ancestry proportions are shown in different plots. Solid black lines represent linear correlations between autosomal and X-chromosome components.</p

Bidimensional plots based on uniparental genomes.

<p>PC analyses based on haplogroup data for Y-chromosome and mtDNA; and MDS analyses based on Y-STR haplotype data and on mtDNA sequence data. Abbreviations: ALG/ALG1: Algiers (this study), ALG2: Algiers (Y-chromosome; [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138453#pone.0138453.ref010" target="_blank">10</a>]), ORN1: Oran (present study), ORN2: Oran (Y-chromosome, [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138453#pone.0138453.ref021" target="_blank">21</a>]; mtDNA, [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138453#pone.0138453.ref017" target="_blank">17</a>]), RGB: Reguibate, ZNT: Zenata, MZB: Mozabite, TZO: Tizi Ouzou</p

Plots for the analysis of genome-wide SNPs.

<p>PC analysis (upper figures) based on autosomal data, and X-chromosome SNPs. ADMIXTURE proportions (bottom figures) at k = 2,3, and 4 based on autosomal data and X-chromosome SNPs. Algeria, stands for general Algerian sample [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138453#pone.0138453.ref003" target="_blank">3</a>]; Mozabite, stands for the Algerian Berber Mozabites [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138453#pone.0138453.ref032" target="_blank">32</a>]; and Zenata, stands for Algerian Berber Zenata (present study).</p

Completing the genetic landscape of Nort Africa: Genomic chatracterization of berber peoples

Trabajo presentado en la 4th Meeting of the Spanish Society of the Evolutionary Biology (SESBE 2013) celebrada en Barcelona del 27 al 29 de noviembre de 2013.N