Inferring genome-wide correlations of mutation fitness effects between populations.
Molecular biology and evolution
The effect of a mutation on fitness may differ between populations depending on environmental and genetic context, but little is known about the factors that underlie such differences. To quantify genome-wide correlations in mutation fitness effects, we developed a novel concept called a joint distribution of fitness effects (DFE) between populations. We then proposed a new statistic w to measure the DFE correlation between populations. Using simulation, we showed that inferring the DFE correlation from the joint allele frequency spectrum is statistically precise and robust. Using population genomic data, we inferred DFE correlations of populations in humans, Drosophila melanogaster, and wild tomatoes. In these species, we found that the overall correlation of the joint DFE was inversely related to genetic differentiation. In humans and D. melanogaster, deleterious mutations had a lower DFE correlation than tolerated mutations, indicating a complex joint DFE. Altogether, the DFE correlation can be reliably inferred, and it offers extensive insight into the genetics of population divergence.
View details for DOI 10.1093/molbev/msab162
View details for PubMedID 34043790
Human-Genetic Ancestry Inference and False Positives in Forensic Familial Searching.
G3 (Bethesda, Md.)
In forensic familial search methods, a query DNA profile is tested against a database to determine if the query profile represents a close relative of a database entrant. One challenge for familial search is that the calculations may require specification of allele frequencies for the unknown population from which the query profile has originated. Allele-frequency misspecification can substantially inflate false-positive rates compared to use of allele frequencies drawn from the same population as the query profile. Here, we use ancestry inference on the query profile to circumvent the high false-positive rates that result from highly misspecified allele frequencies. In particular, we perform ancestry inference on the query profile and make use of allele frequencies based on its inferred genetic ancestry. In a test for sibling matches on profiles that represent unrelated individuals, we demonstrate that false-positive rates for familial search with use of ancestry inference to specify the allele frequencies are similar to those seen when allele frequencies align with the population of origin of a profile. Because ancestry inference is possible to perform on query profiles, the extreme allele-frequency misspecifications that produce the highest false-positive rates can be avoided. We discuss the implications of the results in the context of concerns about the forensic use of familial searching.
View details for DOI 10.1534/g3.120.401473
View details for PubMedID 32586848