Biology subjects

Halgren, A. S.

Publications and source records attributed to Halgren, A. S..

3 recordsLinked to original sources

bioRxiv2022

The Selection Landscape and Genetic Legacy of Ancient Eurasians

The Holocene (beginning [~]12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical, and mental health of present-day populations. Using a dataset of >1600 imputed ancient genomes 1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify major selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported, and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in >400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic, and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, while risk alleles for diabetes and Alzheimers disease are enriched for Western Hunter-gatherer ancestry. Our results suggest that ancient selection and migration were major contributors to the distribution of phenotypic diversity in present-day Europeans.

evolutionary biology↗

bioRxiv2022

Population Genomics of Stone Age Eurasia

Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. To investigate the cross-continental impacts we shotgun-sequenced 317 primarily Mesolithic and Neolithic genomes from across Northern and Western Eurasia. These were imputed alongside published data to obtain diploid genotypes from >1,600 ancient humans. Our analyses revealed a Great Divide genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers (HGs) were highly genetically differentiated east and west of this zone, and the impact of the neolithisation was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacements of HGs in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, while east of the Urals relatedness remained high until [~]4,000 BP, consistent with persistence of localised HG groups. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive but we demonstrate that HGs from the Middle Don region contributed ancestry to them. Yamnaya-groups later admixed with individuals associated with the Globular Amphora Culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a Neolithic steppe cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

evolutionary biology↗

bioRxiv2020

Multielectrode Cortical Stimulation Selectively Induces Unidirectional Wave Propagation in Biophysical/Neural Model

Cortical stimulation is emerging as an experimental tool in basic research and a promising therapy for a range of neuropsychiatric conditions. As multielectrode arrays enter clinical practice, the possibility of using spatiotemporal patterns of electrical stimulation to induce desired physiological patterns has become theoretically possible, but in practice can only be implemented by trial-and-error because of a lack of predictive models. Experimental evidence increasingly establishes travelling waves as fundamental to cortical information-processing, but we lack understanding how to control wave properties despite rapidly improving technologies. This study uses a hybrid biophysical-anatomical and neural-computational model to predict and understand how a simple pattern of cortical surface stimulation could induce directional traveling waves via asymmetric activation of inhibitory interneurons. It reveals local circuit mechanisms to control spatiotemporal cortical dynamics and predicts interventions that can be developed to treat a broad range of cognitive disorders.

neuroscience↗