Tailoring Parameters

When using Bvalcalc to study populations beyond the pre-built templates, it’s important to tailor the popgen parameters to your population of interest.

To save a local copy of one of the templates, see Generate Parameters and open up the Params.py file in your text editor of choice.

Core parameters

x

Scaling factor that modifies N, u, r, and g. Keep as 1 for empirical analysis, only relevant for calculating B to compare against rescaled simulations

Nanc

Ancestral population size, often reported in literature. Can be roughly estimated from nucleotide diversity at neutrally evolving sites, given a mutation rate and no demography (Nanc = pi/4u).

r

Recombination (crossover) mean rate per bp, per generation (sex-averaged), often reported in literature from direct measurement (recombination in pedigrees) or inferred from sequence data. Note you can add a crossover rate map that can modify r across the genome with --rec_map.

u

Mutation mean rate per bp, per generation, often reported in literature from mutation accumulation experiments. Note that the point mutation rate is typically used, though all mutation types with selective effects may contribute to BGS similarly, if considering different mutation types with different DFEs, see Multiple DFEs.

g

Gene conversion initiation mean rate per bp, per generation. Note that on occasion the g * k value is reported in the literature rather than the initiation rate, in which case, the value should be divided by the tract length (k). You can add a gc initiation rate map that can modify g across the genome with --gc_map.

k

Gene conversion tract length (bp). Note that Bvalcalc takes only a single mean value and so does not model a distribution of tract lengths.

DFE parameters

A distribution of fitness effects (DFE) describes the probability of different selective effects for new mutations when they arise. Bvalcalc models a discretized deleterious DFE consisting of four uniform distributions ranging from effectively neutral (f0), to strongly deleterious (f3); beneficial mutations are currently not supported.

See Figure 1 in Johri et al. 2020 for a more detailed explanation of the discretized DFE.

To specify a DFE, provide f0, f1, f2, f3 proportions that represent the DFE for all annotated regions in the BED/GFF input. Note that the proportions must sum to 1, i.e. f0+f1+f2+f3 = 1.

f0

Proportion of effectively neutral mutations with 0 <= | 2*Nanc*s | < 1.

Note that 2*Nanc*s < 5 does not contribute to BGS, see Johri et al. 2020, Bvalcalc will exclude the f0 proportion from BGS calculations.

f1

Proportion of weakly deleterious mutations with 1 <= | 2*Nanc*s | < 10

f2

Proportion of moderately deleterious mutations with 10 <= | 2*Nanc*s | < 100

f3

Proportion of strongly deleterious mutations with 100 <= | 2*Nanc*s |

h

Dominance coefficient of selected alleles. Keep at 0.5 (additive effects) unless literature suggests otherwise

DFE parameters may be reported in the literature as a gamma distribution. Bvalcalc can take gamma distribution parameters which is converted to a discretized DFE to overwrite f0, f1, f2, f3 when --gamma_dfe is specified:

mean, shape, proportion_synonymous

The mean and shape parameters of the gamma DFE, and the proportion of strictly neutral sites in the annotated regions (e.g. synonymous in exon regions).

Demography

Historical population size change as a single step-function can be accounted for with Bvalcalc by adding the --pop_change flag, and setting the following parameters:

Ncur

Current population size, i.e. in the current epoch.

time_of_change

Time in Nanc generations ago that effective population size went from Nanc to Ncur.

Selfing species

Self-fertilizing (selfing) species have different evolutionary dynamics from obligate outcrossers which impact BGS (i.e., B).

The parameters file can be modified for selfing populations by altering population size (Nanc/Ncur), crossover rate (r), gene conversion rate (g) and dominance coefficient by an additional parameter: f, which is Wright’s inbreeding coefficient (F). F can be calculated from the selfing rate (F = S/(2-S)), see Nordborg 2000. Note that the arabidopsis and pfalciparum default templates have the inbreeding parameter included.

For analysis of selfing populations, we recommend tailoring parameters from the selfing template.

Bvalcalc --generate_params selfing