Biology subjects

Schaeffer, S. W.

Publications and source records attributed to Schaeffer, S. W..

5 recordsLinked to original sources

bioRxiv2025

Evolutionary Influences on Local Patterns of Genetic Relatedness

Dimensionality reduction methods, such as Principal Components Analysis (PCA) or Multi-dimensional Scaling (MDS), when applied to genomic data, help to visualize the relatedness of individuals in lower dimensional space and are ubiquitous in population-genetic studies. These analyses use genome-wide patterns of variation to provide an "average" picture of genetic structure and relatedness. However, evolutionary processes result in different patterns of relationship among samples in local genomic regions as compared to the genome-wide aggregate. Recently, these local patterns of relatedness have been used to identify regions under selection and inverted segments. Here, we propose a unifying method to dissect these local deviations in genetic relatedness. Our method, Local Decomposition and Similarity to All Regions (LODESTAR), uses Procrustes Analysis to assess the similarity between local MDS results computed using pairwise allele sharing distances or a set of user-defined points. Given two sets of points, Procrustes Analysis computes the optimal rotation and scaling that fits one set of points onto the other, while maintaining the relative relationship between points within both sets. We use the Procrustes statistic to measure the similarity between the two sets of points. We show how this method can be used to explore local relatedness patterns that mirror sampling geography or population stratification by performing Procrustes analysis between local relatedness plots and coordinates representing sampling geography or between local relatedness plots and the genome-wide relatedness plot, respectively. In addition, we show how the variance of samples in lower-dimensional space can capture regions lacking population structure and inverted segments.

evolutionary biology↗

bioRxiv2022

Genomics of Natural Populations: Gene Conversion Events Reveal Selected Genes within the Inversions of Drosophila pseudoobscura

When adaptive phenotypic variation or QTLs map within an inverted segment of a chromosome, researchers often despair because it is thought that the suppression of crossing over will prevent the discovery of selective target genes that contribute to the establishment of the rearrangement. If an inversion polymorphism is old enough, then the accumulation of gene conversion tracts offers the promise that QTLs or selected loci within inversions can be mapped. This study uses the inversion polymorphism of Drosophila pseudoobscura as a model system to show that gene conversion analysis is a useful tool for mapping selected loci within inversions. D. pseudoobscura has over 30 different chromosomal arrangements on the third chromosome (Muller C) in natural populations and their frequencies vary with changes in environmental habitats. Statistical tests of five D. pseudoobscura gene arrangements identified outlier genes within inverted regions based on local clusters of fixed SNP differences. These outlier genes also had potentially heritable variation, either fixed amino acid differences or differential expression patterns among arrangements. Here, we use genome sequences of the inverted third chromosome (Muller C) to infer 98,443 gene conversion tracts for a total coverage of 142 Mb or 7.2 x coverage of the 19.7 Mb chromosome. We estimated gene conversion tract coverage in the 2,668 genes on Muller C and tested whether the number of genes with significantly low coverage was the same for outlier versus non-outlier loci.. Genes with low gene conversion tract coverage were more frequent in the outlier class than the non-outlier class suggesting that selection removes exchanged DNA from the outlier genes more often than non-outlier genes. These data support the hypothesis that the pattern and organization of genetic diversity on the third chromosome in D. pseudoobscura is consistent with the capture of locally adapted combinations of alleles prior to inversion mutation events.

evolutionary biology↗

bioRxiv2021

Drosophila Evolution over Space and Time (DEST) - A New Population Genomics Resource

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome datasets from natural populations of this species have been published over the last 20 years. A major challenge is the integration of these disparate datasets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution and population structure of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 population samples from over 100 locations in >20 countries on four continents based on a combination of 121 unpublished and 150 previously published genomic datasets. Several of these locations have been sampled at different seasons across multiple years. This dataset, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental meta-data. A web-based genome browser and web portal provide easy access to the SNP dataset. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan dataset. Our resource will enable population geneticists to analyze spatio-temporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.

genomics↗

bioRxiv2018

Extensive recombination suppression and chromosome-wide differentiation of a segregation distorter in Drosophila

Segregation distorters violate Mendelian Inheritance by over-representing themselves in the progeny of carrier individuals and are commonly associated with chromosomal inversions. When distorting alleles are found on sex chromosomes, the progeny of carrier individuals will exhibit skewed sex ratios, as exemplified by the array of Sex-Ratio (SR) distorting chromosomes found in Drosophila. Because of the strong selective pressures such chromosomes are thought to inflict on genomes, segregation distorters and their associated inversions are expected to experience rapid turn-over. However, the SR X-chromosome of Drosophila pseudoobscura is found at high frequencies in natural populations, forms stable latitudinal clines, appears to be unsuppressed, and shows evidence of being quite long-lived. Despite being a historically significant and well-studied segregation distortion system, the mechanisms allowing for the long-term persistence of the D. pseudoobscura SR chromosome remain unclear. Here, we perform a comparative genomic analysis between SR and uninverted standard X-chromosomes in D. pseudoobscura to study its evolutionary history and dynamics. We find a substantial level of differentiation between the SR and standard chromosome and estimate that the associated inversions have likely existed for the entire lifetime of the species (> 2 million generations). Through direct recombination experiments and population genetic analyses, we infer that this high level of differentiation is maintained by a combination of suppressed recombination and epistatic selection. Finally, our data reveal a massive mutational target size for protein and expression level changes specific to SR generated by its three non-overlapping inversions. Together our results imply that the entire SR chromosome in D. pseudoobscura behaves as a single co-adapted gene complex and has been maintained through a combination of suppressed recombination and epistatic selection. This finding highlights the dramatic consequences segregation distorters can have in shaping chromosome-wide patterns of recombination, nucleotide variation, and gene expression.

evolutionary biology↗

bioRxiv2017

Genomics of Natural Populations: Evolutionary Forces that Establish and Maintain Gene Arrangements in Drosophila pseudoosbscura

The evolution of complex traits in heterogeneous environments may shape the order of genes within chromosomes. Drosophila pseudoobscura has a rich gene arrangement polymorphism that allows one to test evolutionary genetic hypotheses about how chromosomal inversions are established in populations. D. pseudoobscura has >30 gene arrangements on a single chromosome that were generated through a series of overlapping inversion mutations with > 10 inversions with appreciable frequencies and wide geographic distributions. This study analyzes the genomic sequences of 54 strains of Drosophila pseudoobscura that carry one of six different chromosomal arrangements to test whether (1) genetic drift, (2) hitchhiking with an adaptive allele, (3) direct effects of inversions to create gene disruptions caused by breakpoints, or (4) indirect effects of inversions in limiting the formation of recombinant gametes are responsible for the establishment of new gene arrangements. We found that the inversion events do not disrupt the structure of protein coding genes at the breakpoints. Population genetic analyses of 2,669 protein coding genes identified 277 outlier loci harboring elevated frequencies of arrangement-specific derived alleles. Significant linkage disequilibrium occurs among distant loci interspersed between regions with low levels of association indicating that distant allelic combinations are held together despite shared polymorphism among arrangements. Outlier genes showing evidence of genetic differentiation between arrangements are enriched for sensory perception and detoxification genes. The data presented here support the indirect effect of inversion hypothesis where chromosomal inversions are favored because they maintain linked associations among multi-locus allelic combinations among different arrangements.

genomics↗