DOI: 10.5061/dryad.qnk98sfnv
title: Main model fits and substitution rate predictions for: A quantitative genetic model of background selection in humans

description: Across the human genome, there are large-scale fluctuations in genetic
 diversity caused by the indirect effects of selection. This can be thought
 of as a “linked selection signal" that reflects the impact of
 selection varying according to the placement of functional regions and
 recombination rates along the genome. Previous work has shown that
 negative selection against the steady influx of new deleterious mutations
 into conserved regions is the predominant mode of selection in humans.
 However, the theoretic model that underpins these results, classic
 Background Selection theory, is only applicable when new mutations are so
 deleterious that they cannot fix in the population. Here, we develop a
 statistical method based on a quantitative genetics view of the linked
 selection, which models the effects of weak draft created according to how
 polygenic additive fitness variance is distributed along the genome. We
 use a recent model that jointly predicts the equilibrium fitness variance
 and substitution rates due to both strong and weakly deleterious
 mutations, we estimate the distribution of fitness effects (DFE) and
 mutation rate across three human populations. While our model can
 accommodate weaker selection, we initially find evidence across three
 human populations of very strong selection against deleterious mutations
 consistent with previous work. However, the corollary predicted
 substitution rates for conserved regions are unreasonably low, and in
 disagreement with observed rates. We hypothesize this could be due to
 selected sites experiencing a further diminished population size due to
 selective interference. When we account for this in our method, we find
 evidence of weakly deleterious mutations in conserved regions which brings
 the predicted substitution rate into agreement with observations. However,
 these models lead to implausibly large mutation rate estimates. Overall,
 while our model of the genomic linked selection signal brings us a step
 towards uniting population and quantitative genetic selection models with
 the substitution process, our work suggests considerable uncertainty
 remains about the processes generating fitness variance in humans.
description: These Python pickle files contain the model outputs from bgspy
 (http://github.com/vsbuffalo/bprime/) for the CADD 6%, CADD 8%, PhastCons Priority, and Feature Priority Models.
description: # Main model fits and substitution rate predictions for: A quantitative
 genetic model of background selection in humans ## Usage Notes All files
 are in in standard Python file formats. To load the pickle files, install
 the accompanying [bprime software available on
 GiHub](https://github.com/vsbuffalo/bprime). Note that all TSV files here
 were written by analyses in Jupyter notebooks that are available on the
 [bprime GitHub page.](http://github.com/vsbuffalo/bprime) ##
 Files ### Model Fits There are pickle files of model results,
 generated by `bgspy collect`. * `cadd6__decode__altgrid.pkl`: CADD 6% *
 `cadd8__decode__altgrid.pkl`: CADD 8% *
 `CDS_genes_phastcons__decode__altgrid.pkl`: Feature Priority *
 `phastcons_CDS_genes__decode__altgrid.pkl`: PhastCons Priority ## Files
 Produced by Sims *
 `empiricalB_chr10__expansion_false__h_0.5__results.npz`: simulation B
 "empirical" B maps for fixed demography *
 `empiricalB_chr10__expansion_1.004_9.3__h_0.5__results.npz`: simulation B
 "empirical" B maps for expansion *
 `bmap_rescaled_hg38_sims_1e-8w_1e-3t_10000step_chr10.pkl`: rescaled B maps
 *
 `bmap__conserved_cds_utrs_phastcons_merged__hapmap__fixed_empiricalB.pkl`:
 theoretic B and B' maps, generated by bgspy ### Files Produced by
 Notebooks ### `main_fits.ipynb` * `main_fits_summary.tsv`: all LOCO R2,
 R2, etc. ### `diversity_data.ipynb` * `accessibilty.tsv`: genome wide
 accessibility stats ### `region_simulations.ipynb` *
 `figure_1_bmap_data.pkl`: Python pickle file of the B maps in Figure 1 *
 `region_simulation_data.tsv.gz`: simulation data containing ratchet rates,
 VA, etc * `region_theory_data.pkl`: theoretic predictions for segments *
 `simulation_ratchet_data.tsv.gz`: simulation ratchet data *
 `theory_simulation_comparison.tsv`: joined table for comparison ###
 `substitution.ipynb` * `phylofit_by_feature.tsv`: divergence data from
 PhyloFit. Also, all raw files are in `data/phylo/pfests_by_feature`. ###
 `method_evaluation.ipynb` * `mle_sim_evaluation_results.tsv`: the joined
 MLE/simulation results for method evaluation figure ### Predicted B'
 maps for the CADD 6% model * `cadd6_summary.tsv`: contains predicted
 B' maps at Mb scale for each population, with pairwise diversity and
 average recombination rates.