Weir, B. S. | Search bioRxiv

bioRxiv2026

Allelic Association Analyses: Estimation Recommendations

We review the rich literature on the estimation of measures of inbreeding, relatedness and population structure, beginning with Sewall Wrights F-statistics and moving onto the descriptive statistics of Masatoshi Nei and Clark Cockerham. The current availability of genome-level single nucleotide variant data is allowing for sophisticated treatments of inferred identity by descent segments and inferred ancestral recombination graphs. Underlying such disparate methods is an emphasis of characterizing the descent status of alleles within and between individuals and populations and we have found allele-sharing statistics a convenient framework for examining the differences and similarities among different estimators. We have been able to resolve some long-standing reported differences among estimators, especially those involving the work of Nei. In the course of our algebraic and empirical treatment of descent measure estimation we have been able to formulate a set of five recommendations. Following the early work of Sewall Wright, we recommend 1. State that descent measures for pairs of alleles are relative to values in a reference set of allele pairs. With this view, we recommend 2. Use estimators that preserve descent measure rankings over different reference sets. Allele-sharing estimators satisfy this recommendation. Reducing genotypic data to allelic data has the benefit of reducing dimensionality, but we recommend 3. If genotypic data are available, avoid having to assume Hardy-Weinberg equilibrium by not reducing them to allelic data. Partly as a consequence of working with genotypic data, we recommend 4. Recognize that allele frequencies do not need to be estimated. Not estimating allele frequencies prevents the confounding of descent estimates for target pairs of alleles by the status of all pairs in a reference set. On the basis of both theoretical and empirical results, finally we recommend 5. Consider both inbreeding and kinship when estimating either one. It is difficult to envisage a natural population with relatedness but no inbreeding, or vice versa.

genomics↗

bioRxiv2025

Using a "one-strain-many-compounds" (OSMAC) approach to screen a collection of diverse fungi from Aotearoa New Zealand for antibacterial activity against Escherichia coli

There is an urgent need to identify new chemical compounds with novel modes of action to help manage the antimicrobial resistance crisis. Fungi are prolific producers of secondary metabolites, including those with antimicrobial properties, and contain biosynthetic gene clusters that awaken only under certain growth conditions. In recent years, a wealth of novel fungal biosynthetic pathways and compounds have been identified, suggesting fungi remain a viable source for developing new antimicrobials. The International Collection of Microorganisms from Plants (ICMP) contains thousands of fungi and bacteria primarily sourced from Aotearoa New Zealand. Here, we report the results of our efforts to screen 32 fungal ICMP isolates for activity against Escherichia coli, a leading cause of deaths attributable to antimicrobial resistance. We used a one strain-many compounds (OSMAC) approach, growing the ICMP isolates on seven different media with different pH and various carbon and nitrogen sources. We also tested the isolates for activity at various ages. Our results indicate that several of the tested fungi possess anti-E. coli activity and are suitable for further study, including the aero-aquatic Ascomycete Hyaloscypha sp. ICMP 16864. Our results also provide further strong evidence for the impact of media on both fungal growth and bioactivity.

microbiology↗

bioRxiv2018

Molecular Evolution of Pseudomonas syringae Type III Secreted Effector Proteins

Diverse Gram-negative pathogens like Pseudomonas syringae employ type III secreted effector (T3SE) proteins as primary virulence factors that combat host immunity and promote disease. T3SEs can also be recognized by plant hosts and activate an effector triggered immune (ETI) response that shifts the interaction back towards plant immunity. Consequently, T3SEs are pivotal in determining the virulence potential of individual P. syringae strains, and ultimately restrict P. syringae pathogens to a subset of potential hosts that are unable to recognize their repertoires of T3SEs. While a number of effector families are known to be present in the P. syringae species complex, one of the most persistent challenges has been documenting the complex variation in T3SE contents across a diverse collection of strains. Using the entire pan-genome of 494 P. syringae strains isolated from more than 100 hosts, we conducted a global analysis of all known and putative T3SEs. We identified a total of 14,613 T3SEs, 4,636 of which were unique at the amino acid level, and show that T3SE repertoires of different P. syringae strains vary dramatically, even among strains isolated from the same hosts. We also find that dramatic diversification has occurred within many T3SE families, and in many cases find strong signatures of positive selection. Furthermore, we identify multiple gene gain and loss events for several families, demonstrating an important role of horizontal gene transfer (HGT) in the evolution of P. syringae T3SEs. These analyses provide insight into the evolutionary history of P. syringae T3SEs as they co-evolve with the host immune system, and dramatically expand the database of P. syringae T3SEs alleles.

evolutionary biology↗

bioRxiv2016

A unified characterization of population structure and relatedness.

Many population genetic activities, ranging from evolutionary studies to association mapping to forensic identification, rely on appropriate estimates of population structure or relatedness. All applications require recognition that quantities with an underlying meaning of allelic identity by descent are not defined in an absolute sense, but instead are made \"relative to\" some set of alleles other than the target set. The early Weir and Cockerham FST estimate made explicit that the reference set of alleles was across independent populations. Standard kinship estimates have an implicit assumption that pairs of individuals in a study sample, other than the target pair, are unrelated, whereas other estimates assume alleles within individuals are not identical by descent. However, populations lose independence when there is migration between them, and when individuals in a study are related it is difficult to see how they can also be non-inbred. We have therefore re-cast our treatments of population structure, relatedness and inbreeding to make explicit that the parameters of interest involve differences of probabilities of identity by descent in the target and the reference sets of alleles and so can be negative. We take the reference set to be for the population from which study individuals have been sampled. We provide simple moment estimates of these parameters, phrased in terms of allele matching within and between individuals for relatedness and inbreeding, or within and between populations for population structure. A multi-level hierarchy of alleles within individuals, alleles between individuals within populations, and alleles between populations allows a unified treatment of relatedness and population structure. Our new estimates appear to be sensitive to rare or private variants, to give indications of the effects of natural selection, and to be appropriate for use in association studies.

genetics↗

bioRxiv2016

A Unified Characterization ofPopulation Structure and Relatedness

Many population genetic activities, ranging from evolutionary studies to association mapping to forensic identification, rely on appropriate estimates of population structure or relatedness. All applications require recognition that quantities with an underlying meaning of allelic identity by descent are not defined in an absolute sense, but instead are made \"relative to\" some set of alleles other than the target set. The early Weir and Cockerham FST estimate made explicit that the reference set of alleles was across independent populations. Standard kinship estimates have an implicit assumption that pairs of individuals in a study sample, other than the target pair, are unrelated, whereas other estimates assume alleles within individuals are not identical by descent. However, populations lose independence when there is migration between them, and when individuals in a study are related it is difficult to see how they can also be non-inbred. We have therefore re-cast our treatments of population structure, relatedness and inbreeding to make explicit that the parameters of interest involve differences of probabilities of identity by descent in the target and the reference sets of alleles and so can be negative. We take the reference set to be for the population from which study individuals have been sampled. We provide simple moment estimates of these parameters, phrased in terms of allele matching within and between individuals for relatedness and inbreeding, or within and between populations for population structure. A multi-level hierarchy of alleles within individuals, alleles between individuals within populations, and alleles between populations allows a unified treatment of relatedness and population structure. Our new estimates appear to be sensitive to rare or private variants, to give indications of the effects of natural selection, and to be appropriate for use in association studies.

genetics↗