simDominanceModifier

Our simulation model builds off of Porter et al. (2017) and is based on the premise that transcription factors (TF) and binding sites behave according to the thermodynamic and kinetic properties of molecular interactions.

Our diploid model consists of two unlinked interacting genes, A and B. The alternative alleles of Gene A codes for TFs that have opposite effects on the expression of Gene B, and Gene B’s expression is under additive sexually antagonistic selection. Gene A’s experession is determined by cis-regulatory binding site that can mutate/evolve toward being a better binder of either the male- or female-limited regulatory stimuli, approximating sex-limited hormones. Gene B's expression is determined by cis-regulatory binding site that can mutate/evolve toward being a better binder to either of the TFs expressed by Gene A. Finally, fitness is determined by the expression of Gene B, where females and males benefit from increased and decreased expression, respectively. There is no dominance coefficient; sex-specific dominance reversal for fitness between Gene A's alleles evolves at the genotype-expression level as an emergent property of their fractional occupancy of Gene B’s binding site. Populations are simulated following the standard Wright-Fisher model with discrete, non-overlapping generations undergoing mutation, reproduction and selection.

Please refer to our publication (Grieshop et al. 2024) and supplementary documents for a detailed description of the model and its parameters.

Dependencies

• Python 3.10.9 (https://www.python.org/)
• Pandas 1.5.2 (https://pandas.pydata.org/)
• Numpy 1.23.5 (https://numpy.org/)

Usage

usage: simDominanceModifier.py [-h] -n NPROC -p PARFILE

options:
  -h, --help            show this help message and exit
  -n NPROC, --NPROC NPROC
                        Number of processes to run simultaneously
  -p PARFILE, --PARFILE PARFILE
                        CSV file containing parameters for simulations

Input parameter file

The script requires a CSV file containing parameters for each run (-p PARFILE). Each row of the parameter file represents an independent simulation. Each row must contain all the parameters listed below. Please refer to example_parameter_file.csv for guidance.

Output files

Three CSV files are output for each run of the similation in the directory specificied by DIR of the parameter file. The output of each run with be prefixed with {NAME}.{replicate number} as specified by NAME and REP in the parameter file.

Summary results of simulation run: {NAME}.{replicate number}.general.csv

The file outputs a variety of summary statistics for the population every 10^th generation of the simulation. Refer to the table below for descriptions of each column in the file.

Distribution of values for the binding and protein coding sites: {NAME}.{replicate number}.dist.csv

This file outputs the occurence for each allelic value of the binding site at gene A and the binding site of gene B for every 10^th generation of the simulation. It also outputs the number of females and males binned by their standardized expression levels of Gene B. Refer to the table below for descriptions of each column in the file.

Genotype and phenotype of each individual: {NAME}.{replicate number}.indiv.csv

This file outputs properties for each individual at the final generation of the simumlation. Each row of this file represents a separate individual. Refer to the table below for descriptions of each column in the file.

References

Porter AH, Johnson NA, Tulchinsky A. (2017) A New Mechanism for Mendelian Dominance in Regulatory Genetic Pathways: Competitive Binding by Transcription Factors. Genetics 205, 101–112.

Grieshop K, Ho EKH, Kasimatis KR. (2024) Dominance reversals: the resolution of genetic conflict and maintenance of genetic variation. Proceedings of the Royal Society B, 291(2018), p20232816. (doi: 10.1098/rspb.2023.2816)