Published December 20, 2022 | Version v1
Journal article Open

Modeling the spatiotemporal spread of beneficial alleles using ancient genomes

Description

Ancient genome sequencing technologies now provide the opportunity to study natural selection in unprecedented detail. Rather than making inferences from indirect footprints left by selection in present-day genomes, we can directly observe whether a given allele was present or absent in a particular region of the world at almost any period of human history within the last 10,000 years. Methods for studying selection using ancient genomes often rely on partitioning individuals into discrete time periods or regions of the world. However, a complete understanding of natural selection requires more nuanced statistical methods which can explicitly model allele frequency changes in a continuum across space and time. Here we introduce a method for inferring the spread of a beneficial allele across a landscape using two-dimensional partial differential equations. Unlike previous approaches, our framework can handle time-stamped ancient samples, as well as genotype likelihoods and pseudohaploid sequences from low-coverage genomes. We apply the method to a panel of published ancient West Eurasian genomes to produce dynamic maps showcasing the inferred spread of candidate beneficial alleles over time and space. We also provide estimates for the strength of selection and diffusion rate for each of these alleles. Finally, we high-light possible avenues of improvement for accurately tracing the spread of beneficial alleles in more complex scenarios.

Data availability

The current manuscript is a computational study, therefore no data have been generated for this manuscript. Software code along with publicly available data used for this study are deposited to GitHub: https://github.com/RasaMukti/stepadna/tree/main/reproducibles (copy archived at swh:1:rev:d024767648d873f329a8e17fcaf6034c99157120).

The following previously published data sets were used:

Reich D Mallick S (2019) Allen Ancient DNA ID AADR. Allen Ancient DNA Resource (AADR). https://reich.hms.harvard.edu/allen-ancient-dna-resource-aadr-downloadable-genotypes-present-day-and-ancient-dna-data

Bergström A McCarthy SA Hui R Almarri MA Ayub Q Danecek P Chen Y Felkel S Hallast P Kamm J Blanché H Deleuze JF Cann H Mallick S Reich D Sandhu MS Skoglund P Scally A Xue Y Durbin R Tyler-Smith C (2020) EMBL-EBI ID HGDP. Human Genome Diversity Panel. http://ftp.1000genomes.ebi.ac.uk/vol1/ftp/data_collections/HGDP/

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Additional details

Identifiers

DOI
10.7554/eLife.73767
Other
oai:uchicago.tind.io:9860

Funding

Villum Fonden
00025300
Lundbeckfonden
R302-2018-2155
Novo Nordisk Fonden
NNF18SA0035006
Carlsbergfondet
CF19-0712
National Institutes of Health
R01 GM132383
Novo Nordisk Fonden
NNF22OC0076816
European Research Council
951385

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Human Genetics