qpAdm is a statistical tool that is often used for testing large sets of alternative admixture models for a target population. Despite its popularity, qpAdm remains untested on 2D stepping stone landscapes and in situations with low prestudy odds (low ratio of true to false models). We tested high-throughput qpAdm protocols with typical properties such as number of source combinations per target, model complexity, model feasibility criteria, etc. Those protocols were applied to admixture graph-shaped and stepping stone simulated histories sampled randomly or systematically. We demonstrate that false discovery rates of high-throughput qpAdm protocols exceed 50% for many parameter combinations since: (1) prestudy odds are low and fall rapidly with increasing model complexity; (2) complex migration networks violate the assumptions of the method; hence, there is poor correlation between qpAdm P-values and model optimality, contributing to low but nonzero false-positive rate and low power; and (3) although admixture fraction estimates between 0 and 1 are largely restricted to symmetric configurations of sources around a target, a small fraction of asymmetric highly nonoptimal models have estimates in the same interval, contributing to the false-positive rate. We also reinterpret large sets of qpAdm models from 2 studies in terms of source-target distance and symmetry and suggest improvements to qpAdm protocols: (1) temporal stratification of targets and proxy sources in the case of admixture graph-shaped histories, (2) focused exploration of few models for increasing prestudy odds; and (3) dense landscape sampling for increasing power and stringent conditions on estimated admixture fractions for decreasing the false-positive rate.

• Klíčová slova
• qpAdm, admixture graphs, archaeogenetics, genetic admixture, simulation, stepping stone models,
• MeSH
• lidé MeSH
• modely genetické * MeSH
• populační genetika * metody   MeSH
• software * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Located in the southwestern corner of Europe, the Iberian Peninsula is separated from the rest of the continent by the Pyrenees Mountains and from Africa by the Strait of Gibraltar. This geographical position may have conditioned distinct selective pressures compared to the rest of Europe and influenced differential patterns of gene flow. In this work, we analyse 704 whole-genome sequences from the GCAT reference panel to quantify gene flow into Spain from various historical sources and identify the top signatures of positive (adaptive) selection. While we found no clear evidence of a 16th-century admixture event putatively related to the French diaspora during the Wars of Religion, we detected signals of North African admixture matching the Muslim period and the subsequent Christian Reconquista. Notably, besides finding that well-known candidate genes previously described in Eurasians also seem to be adaptive in Spain, we discovered novel top candidates for positive selection putatively associated with immunity and diet (UBL7, SMYD1, VAC14 and FDFT1). Finally, local ancestry deviation analysis revealed that the MHCIII genomic region underwent post-admixture selection following the post-Neolithic admixture with Steppe ancestry.

• Klíčová slova
• Demography, Human adaptation, Positive selection, Post-admixture selection, Selection scan, Spanish population,
• MeSH
• demografie MeSH
• fyziologická adaptace * genetika   MeSH
• genom lidský MeSH
• kohortové studie MeSH
• lidé MeSH
• populační genetika MeSH
• selekce (genetika) MeSH
• tok genů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Španělsko MeSH

The Yamnaya archaeological complex appeared around 3300 BC across the steppes north of the Black and Caspian Seas, and by 3000 BC it reached its maximal extent, ranging from Hungary in the west to Kazakhstan in the east. To localize Yamnaya origins among the preceding Eneolithic people, we assembled ancient DNA from 435 individuals, demonstrating three genetic clines. A Caucasus-lower Volga (CLV) cline suffused with Caucasus hunter-gatherer1 ancestry extended between a Caucasus Neolithic southern end and a northern end at Berezhnovka along the lower Volga river. Bidirectional gene flow created intermediate populations, such as the north Caucasus Maikop people, and those at Remontnoye on the steppe. The Volga cline was formed as CLV people mixed with upriver populations of Eastern hunter-gatherer2 ancestry, creating hypervariable groups, including one at Khvalynsk. The Dnipro cline was formed when CLV people moved west, mixing with people with Ukraine Neolithic hunter-gatherer ancestry3 along the Dnipro and Don rivers to establish Serednii Stih groups, from whom Yamnaya ancestors formed around 4000 BC and grew rapidly after 3750-3350 BC. The CLV people contributed around four-fifths of the ancestry of the Yamnaya and, entering Anatolia, probably from the east, at least one-tenth of the ancestry of Bronze Age central Anatolians, who spoke Hittite4,5. We therefore propose that the final unity of the speakers of 'proto-Indo-Anatolian', the language ancestral to both Anatolian and Indo-European people, occurred in CLV people some time between 4400 BC and 4000 BC.

• MeSH
• běloši genetika   dějiny   MeSH
• dějiny starověku MeSH
• Evropané MeSH
• fylogeneze MeSH
• haplotypy MeSH
• lidé MeSH
• migrace lidstva * dějiny   MeSH
• mitochondriální DNA analýza   MeSH
• populační genetika * MeSH
• řeky MeSH
• starobylá DNA analýza   MeSH
• tok genů MeSH
• Check Tag
• dějiny starověku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• Názvy látek
• mitochondriální DNA MeSH
• starobylá DNA MeSH

qpAdm is a statistical tool that is often used for testing large sets of alternative admixture models for a target population. Despite its popularity, qpAdm remains untested on two-dimensional stepping-stone landscapes and in situations with low pre-study odds (low ratio of true to false models). We tested high-throughput qpAdm protocols with typical properties such as number of source combinations per target, model complexity, model feasibility criteria, etc. Those protocols were applied to admixture-graph-shaped and stepping-stone simulated histories sampled randomly or systematically. We demonstrate that false discovery rates of high-throughput qpAdm protocols exceed 50% for many parameter combinations since: 1) pre-study odds are low and fall rapidly with increasing model complexity; 2) complex migration networks violate the assumptions of the method, hence there is poor correlation between qpAdm p-values and model optimality, contributing to low but non-zero false positive rate and low power; 3) although admixture fraction estimates between 0 and 1 are largely restricted to symmetric configurations of sources around a target, a small fraction of asymmetric highly non-optimal models have estimates in the same interval, contributing to the false positive rate. We also re-interpret large sets of qpAdm models from two studies in terms of source-target distance and symmetry and suggest improvements to qpAdm protocols: 1) temporal stratification of targets and proxy sources in the case of admixture-graph-shaped histories; 2) focused exploration of few models for increasing pre-study odds; 3) dense landscape sampling for increasing power and stringent conditions on estimated admixture fractions for decreasing the false positive rate.

• Klíčová slova
• admixture graphs, archaeogenetics, genetic admixture, qpAdm, simulation, stepping-stone models,
• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

The Yamnaya archaeological complex appeared around 3300BCE across the steppes north of the Black and Caspian Seas, and by 3000BCE reached its maximal extent from Hungary in the west to Kazakhstan in the east. To localize the ancestral and geographical origins of the Yamnaya among the diverse Eneolithic people that preceded them, we studied ancient DNA data from 428 individuals of which 299 are reported for the first time, demonstrating three previously unknown Eneolithic genetic clines. First, a "Caucasus-Lower Volga" (CLV) Cline suffused with Caucasus hunter-gatherer (CHG) ancestry extended between a Caucasus Neolithic southern end in Neolithic Armenia, and a steppe northern end in Berezhnovka in the Lower Volga. Bidirectional gene flow across the CLV cline created admixed intermediate populations in both the north Caucasus, such as the Maikop people, and on the steppe, such as those at the site of Remontnoye north of the Manych depression. CLV people also helped form two major riverine clines by admixing with distinct groups of European hunter-gatherers. A "Volga Cline" was formed as Lower Volga people mixed with upriver populations that had more Eastern hunter-gatherer (EHG) ancestry, creating genetically hyper-variable populations as at Khvalynsk in the Middle Volga. A "Dnipro Cline" was formed as CLV people bearing both Caucasus Neolithic and Lower Volga ancestry moved west and acquired Ukraine Neolithic hunter-gatherer (UNHG) ancestry to establish the population of the Serednii Stih culture from which the direct ancestors of the Yamnaya themselves were formed around 4000BCE. This population grew rapidly after 3750-3350BCE, precipitating the expansion of people of the Yamnaya culture who totally displaced previous groups on the Volga and further east, while admixing with more sedentary groups in the west. CLV cline people with Lower Volga ancestry contributed four fifths of the ancestry of the Yamnaya, but also, entering Anatolia from the east, contributed at least a tenth of the ancestry of Bronze Age Central Anatolians, where the Hittite language, related to the Indo-European languages spread by the Yamnaya, was spoken. We thus propose that the final unity of the speakers of the "Proto-Indo-Anatolian" ancestral language of both Anatolian and Indo-European languages can be traced to CLV cline people sometime between 4400-4000 BCE.

• Publikační typ
• časopisecké články MeSH
• preprinty MeSH