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Lookup NU author(s): Dr Jere KoskelaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Recent breakthroughs have enabled the accurate inference of large-scale genealogies. Through modelling the impact of recombination on the correlation structure between genealogical local trees, we evaluate how this structure is reconstructed by leading approaches. Despite identifying pervasive biases, we show that applying a simple correction recovers the desired distributions for one algorithm, Relate. We develop a statistical test to identify clades spanning unexpectedly long genomic regions, likely reflecting regional suppression of recombination in some individuals. Our approach allows a systematic scan for inter-individual recombination rate variation at an intermediate scale, between genome-wide differences and individual hotspots. Using genealogies reconstructed with Relate for 2 504 human genomes, we identify 50 regions possessing clades with unexpectedly long genomic spans (p < 1・10−12). The strongest signal corresponds to a known inversion on chromosome 17. The second strongest uncovers a novel 760kb inversion on chromosome 10, common (21%) in S. Asians and correlated with GWAS hits for a range of phenotypes. Other regions indicate additional genomic rearrangements: inversions (8), copy number changes (2), or other variants (12). The remaining regions appear to reflect recombination suppression by previously unevidenced mechanisms. They are enriched for precisely spanning single genes (p = 5・10−10), specifically those expressed in male gametogenesis, and for eQTLs (p = 2・10−3). This suggests an extension of previously hypothesised crossover suppression within meiotic genes, towards a model of suppression varying across individuals with different expression levels. Our methods can be readily applied to other species, showing that genealogies offer previously untapped potential to study structural variation and other phenomena impacting evolution
Author(s): Ignatieva A, Favero M, Koskela J, Sant J, Myers SR
Publication type: Article
Publication status: Published
Journal: Molecular Biology and Evolution
Year: 2025
Volume: 42
Issue: 9
Print publication date: 01/09/2025
Online publication date: 06/08/2025
Acceptance date: 07/07/2025
Date deposited: 19/08/2025
ISSN (electronic): 1537-1719
Publisher: Oxford University Press
URL: https://doi.org/10.1093/molbev/msaf190
DOI: 10.1093/molbev/msaf190
ePrints DOI: 10.57711/beg9-1095
Data Access Statement: Code implementing DoLoReS is publicly available at github.com/a-ignatieva/dolores. Scripts used to produce and analyse the simulated and 1KGP data are publicly available at github. com/a-ignatieva/dolores-paper. Simulated data and 1KGP results are publicly available at doi.org/10.6084/m9.figshare.29256770.v1.
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