Biology subjects

Freyman, W. A.

Publications and source records attributed to Freyman, W. A..

14 recordsLinked to original sources

bioRxiv2026

A tribal-scale phylogenomic perspective on ancestry and major lineages of the allotetraploid Hawaiian silversword alliance (Madieae, Compositae)

Premise of the studyDisentangling ancestry of insular plant lineages is important for resolving their evolutionary histories but often complicated by polyploidy, an overrepresented condition in remote island floras. A phylogenomic approach was used to study the origin of subgenomes of the tetraploid Hawaiian silversword alliance and advance understanding of this major example of adaptive radiation. MethodsSequences from 461 target-capture nuclear loci were phased to subgenomes of the tetraploid silversword alliance (Compositae) using assemblies from diploid North American tarweeds as clade references. Maximum-likelihood and multispecies- coalescent analyses of phased loci were conducted with and without representatives of diploid lineages throughout tribe Madieae. Key resultsAn allopolyploid origin of the silversword alliance was corroborated, with Subgenome-A phased consistently to Anisocarpus madioides and Subgenome-B phased to diploid representatives of each of three other sublineages of the "Madia" lineage. Phylogenomic analyses indicate Anisocarpus madioides is more closely related to Subgenome-A than to other tarweeds, including Anisocarpus scabridus. Subgenome trees for the silversword alliance are highly congruent with each other and with structural genomic differences between lineages. ConclusionsThese results indicate an even closer relationship of the silversword alliance to extant California tarweeds than previously understood. Anisocarpus madioides has chromosomal and ecological traits anticipated in an ancestor of the silversword alliance, with the widest geographic range among perennial tarweeds and sticky bracts completely enveloping fruits. Within the silversword alliance, robust support for four major clades reinforces the phylogenetic value of chromosomal interchanges and taxonomic insights by Asa Gray regarding the enigmatic liana Dubautia latifolia.

evolutionary biology↗

bioRxiv2025

Bayesian inference of population structure using identity-by-descent-based stochastic block models

Fine-scale population structure is increasingly studied by clustering identity-by-descent (IBD) haplotypes, yet most current approaches rely on heuristic, modularity-based algorithms that can over-partition noisy IBD graphs and provide no explicit measure of uncertainty. We introduce a fully Bayesian framework that models IBD sharing with a generative planted-partition stochastic block model (PPSBM). To benchmark accuracy, we simulated genomes under recent population divergence and compared PPSBM estimates with those from the widely used Leiden community-detection algorithm. The PPSBM correctly assigned 81.0% of individuals on average versus 67.0% for Leiden, outperforming Leiden in 92.0% of replicates. Posterior probabilities from the PPSBM reflected patterns of recent shared ancestry or admixture, whereas Leiden tended to merge such clusters or assign individuals deterministically. Furthermore, we applied the method to the genomes of 63,196 individuals to reveal fine-scale population structure in Mexico, including multiple indigenous communities and diasporic groups such as Lebanese Mexicans and Syrian Jewish Mexicans. Our results demonstrate that a probabilistic, IBD-based PPSBM yields more accurate and biologically interpretable population assignments than popular heuristic methods, while simultaneously quantifying uncertainty and accommodating admixed genomes. The method scales to thousands of individuals and provides a principled foundation for downstream demographic inference and association studies in the presence of subtle structure.

genetics↗

bioRxiv2024

Reconstructing parent genomes using siblings and other relatives

Reconstructing the DNA of ancestors from their descendants has the potential to empower phenotypic analyses (including association and genetic nurture studies), improve pedigree reconstruction, and shed light on the ancestral population and phenotypes of ancestors. We developed HAPI-RECAP, a method that reconstructs the DNA of parents from full siblings and their relatives. This tool leverages HAPI2s output, a new phasing approach that applies to siblings (and optionally one or both parents) and reliably infers parent haplotypes but does not link the ungenotyped parents DNA across chromosomes or between segments flanking ambiguities. By combining IBD between the reconstructed parents and the relatives, HAPI-RECAP resolves the source parent of these segments. Moreover, the method exploits crossovers the children inherited and sex-specific genetic maps to infer the reconstructed parents sexes. We validated these methods on research participants from both 23andMe, Inc. and the San Antonio Mexican American Family Studies. Given data for one parent, HAPI2 reconstructs large fractions of the missing parents DNA, between 77.6% and 99.97% among all families, and 90.3% on average in three- and four-child families. When reconstructing both parents, HAPI-RECAP inferred between 33.2% and 96.6% of the parents genotypes, averaging 70.6% in four-child families. Reconstructed genotypes have average error rates < 10-3, or comparable to those from direct genotyping. HAPI-RECAP inferred the parent sexes 100% correctly given IBD-linked segments and can also reconstruct parents without any IBD. As datasets grow in size, more families will be implicitly collected; HAPI-RECAP holds promise to enable high quality parent genotype reconstruction.

bioinformatics↗

bioRxiv2024

Phasing millions of samples achieves near perfect accuracy, enabling parent-of-origin classification of variants

Haplotype phasing, the process of determining which genetic variants are physically located on the same chromosome, is crucial for various genetic analyses. In this study, we first benchmark SHAPEIT and Beagle, two state-of-the-art phasing methods, on two large datasets: > 8 million diverse, research-consented 23andMe, Inc. customers and the UK Biobank (UKB). We find that both perform exceptionally well. Beagles median switch error rate (SER) (after excluding single SNP switches) in white British trios from UKB is 0.026% compared to 0.00% for European ancestry 23andMe research participants; 55.6% of European ancestry 23andMe research participants have zero non-single SNP switches, compared to 42.4% of white British trios. South Asian ancestry 23andMe research participants have the highest median SER amongst the 23andMe populations, but it is still remarkably low at 0.46%. We also investigate the relationship between identity-by-descent (IBD) and SER, finding that switch errors tend to occur in regions of little or no IBD segment coverage. SHAPEIT and Beagle excel at intra-chromosomal phasing, but lack the ability to phase across chromosomes, motivating us to develop an inter-chromosomal phasing method, called HAPTIC (HAPlotype TIling and Clustering), that assigns paternal and maternal variants discretely genome-wide. Our approach uses identity-by-descent (IBD) segments to phase blocks of variants on different chromosomes. HAPTIC represents the segments a focal individual shares with their relatives as nodes in a signed graph and performs bipartite clustering on the signed graph using spectral clustering. We test HAPTIC on 1022 UKB trios, yielding a median phase error of 0.08% in regions covered by IBD segments (33.5% of sites). We also ran HAPTIC in the 23andMe database and found a median phase error rate (the rate of mismatching alleles between the inferred and true phase) of 0.92% in Europeans (93.8% of sites) and 0.09% in admixed Africans (92.7% of sites). HAPTICs precision depends heavily on data from relatives, so will increase as datasets grow larger and more diverse. HAPTIC enables analyses that require the parent-of-origin of variants, such as association studies and ancestry inference of untyped parents.

bioinformatics↗

bioRxiv2023

Commonly used Bayesian diversification-rate models produce biologically meaningful differences on empirical phylogenies

Identifying along which lineages shifts in diversification rates occur is a central goal of comparative phylogenetics; these shifts may coincide with key evolutionary events such as the development of novel morphological characters, the acquisition of adaptive traits, polyploidization or other structural genomic changes, or dispersal to a new habitat and subsequent increase in environmental niche space. However, while multiple methods now exist to estimate diversification rates and identify shifts using phylogenetic topologies, the appropriate use and accuracy of these methods is hotly debated. Here we test whether five Bayesian methods--Bayesian Analysis of Macroevolutionary Mixtures (BAMM), two implementations of the Lineage-Specific Birth-Death-Shift model (LSBDS and PESTO), the approximate Multi-Type Birth-Death model (MTBD; implemented in BEAST2), and the cladogenetic diversification rate shift model (CLaDS2)--produce comparable results. We apply each of these methods to a set of 65 empirical time-calibrated phylogenies and compare inferences of speciation rate, extinction rate, and net diversification rate. We find that the five methods often infer different speciation, extinction, and net-diversification rates. Consequently, these different estimates may lead to different interpretations of the macroevolutionary dynamics. The different estimates can be attributed to fundamental differences among the compared models. Therefore, the inference of shifts in diver-sification rates is strongly method-dependent. We advise biologists to apply multiple methods to test the robustness of the conclusions or to carefully select the method based on the validity of the underlying model assumptions to their particular empirical system. Lay SummaryUnderstanding why some groups of organisms have more species than others is key to understanding the origin of biodiversity. Theory and empirical evidence suggest that multiple distinct historical events--such as the evolution of particular morphological features (e.g., the flower, the tetrapod limb) and competition amongst species--can produce this pattern of divergent species richness. Identifying when and where on the tree of life shifts in diversification rates occur is important for explaining the origin of modern-day biodiversity and understanding how disparity among species evolves. Several statistical methods have been developed to infer diversification rates and identify these shifts. While these methods each attempt to make inferences about changes in the tempo of diversification, they differ in their underlying statistical models and assumptions. Here we test if these methods draw similar conclusions using a dataset of 65 time-calibrated phylogenies from across multicellular life. We find that inferences of where rate shifts occur strongly depends on the chosen method. Therefore, biologists should choose the model whose assumptions they believe to be the most valid and justify their model choice a priori, or consider using several independent methods to test an evolutionary hypothesis.

evolutionary biology↗

bioRxiv2023

adequaSSE: Model Adequacy Testing for Trait-Dependent Diversification Models

The presence of large variation in speciation and extinctin rates across the tree of life has long been hypothesized to be driven by the evolution of traits that affect diversification. To test such hypotheses, phylogenetic biologists have developed a wide class of state-dependent birth-death processes that jointly model trait evolution and the diversification process. However, it has since been shown that these models are sensitive to falsely linking traits to diversification. Here we present a Bayesian approach to test the adequacy of statedependent birth-death models by statistically checking whether they describe the variation observed in the data. Our method generates posterior predictive distributions for a suite of informative test statistics, providing a general framework for testing diversification processes and models of trait evolution. We simulate data sets under different violations of model assumptions and find that our approach successfully detects the inadequacy of the model for them. We further show that the manner in which a model fails to fit the data can reveal insights into the processes of trait evolution and diversification.

evolutionary biology↗

bioRxiv2021

RevGadgets: an R Package for visualizing Bayesian phylogenetic analyses from RevBayes

O_LIStatistical phylogenetic methods are the foundation for a wide range of evolutionary and epidemiological studies. However, as these methods grow increasingly complex, users often encounter significant challenges with summarizing, visualizing, and communicating their key results. C_LIO_LIWe present RevGadgets, an R package for creating publication-quality figures from the results of a large variety of phylogenetic analyses performed in RevBayes (and other phylogenetic software packages). C_LIO_LIWe demonstrate how to use RevGadgets through a set of vignettes that cover the most common use cases that researchers will encounter. C_LIO_LIRevGadgets is an open-source, extensible package that will continue to evolve in parallel with RevBayes, helping researchers to make sense of and communicate the results of a diverse array of analyses. C_LI [Bayesian phylogenetics, data visualization, R, RevBayes]

evolutionary biology↗

bioRxiv2021

Bonsai: An efficient method for inferring large human pedigrees from genotype data

1.AO_SCPLOWBSTRACTC_SCPLOWPedigree inference from genotype data is a challenging problem, particularly when pedigrees are sparsely sampled and individuals may be distantly related to their closest genotyped relatives. We present a new method that infers small pedigrees of close relatives and then assembles them into larger pedigrees. To assemble large pedigrees, we introduce several new formulas and tools including a new likelihood for the degree separating two small pedigrees, a method for detecting individuals who share background identity-by-descent (IBD) that does not reflect recent common ancestry, and a method for identifying the ancestral branches through which distant relatives are connected. Our method also takes several new approaches that help to improve the accuracy and efficiency of pedigree inference. In particular, we incorporate age information directly into the likelihood rather than using ages only for consistency checks and we employ a heuristic branch-and-bound-like approach to more efficiently explore the space of possible pedigrees. Together, these approaches make it possible to construct large pedigrees that are challenging or intractable for current inference methods. The new method, Bonsai, is available at https://github.com/23andMe/bonsaitree.

genetics↗

bioRxiv2020

homologizer: Phylogenetic phasing of gene copies into polyploid subgenomes

SummaryO_LIOrganisms such as allopolyploids and F1 hybrids contain multiple distinct subgenomes, each potentially with its own evolutionary history. These organisms present a challenge for multilocus phylogenetic inference and other analyses since it is not apparent which gene copies from different loci are from the same subgenome and thus share an evolutionary history. C_LIO_LIHere we introduce homologizer, a flexible Bayesian approach that uses a phylogenetic framework to infer the phasing of gene copies across loci into their respective subgenomes. C_LIO_LIThrough the use of simulation tests we demonstrate that homologizer is robust to a wide range of factors, such as incomplete lineage sorting and the phylogenetic informativeness of loci. Furthermore, we establish the utility of homologizer on real data, by analyzing a multilocus dataset consisting of nine diploids and 19 tetraploids from the fern family Cystopteridaceae. C_LIO_LIFinally, we describe how homologizer may potentially be used beyond its core phasing functionality to identify non-homologous sequences, such as hidden paralogs or contaminants. C_LI

evolutionary biology↗

bioRxiv2020

Fast and robust identity-by-descent inference with the templated positional Burrows-Wheeler transform

Estimating the genomic location and length of identical-by-descent (IBD) segments among individuals is a crucial step in many genetic analyses. However, the exponential growth in the size of biobank and direct-to-consumer (DTC) genetic data sets makes accurate IBD inference a significant computational challenge. Here we present the templated positional Burrows-Wheeler transform (TPBWT) to make fast IBD estimates robust to genotype and phasing errors. Using haplotype data simulated over pedigrees with realistic genotyping and phasing errors we show that the TPBWT outperforms other state-of-the-art IBD inference algorithms in terms of speed and accuracy. For each phase-aware method, we explore the false positive and false negative rates of inferring IBD by segment length and characterize the types of error commonly found. Our results highlight the fragility of most phased IBD inference methods; the accuracy of IBD estimates can be highly sensitive to the quality of haplotype phasing. Additionally we compare the performance of the TPBWT against a widely used phase-free IBD inference approach that is robust to phasing errors. We introduce both in-sample and out-of-sample TPBWT-based IBD inference algorithms and demonstrate their computational efficiency on massive-scale datasets with millions of samples. Furthermore we describe the binary file format for TPBWT-compressed haplotypes that results in fast and efficient out-of-sample IBD computes against very large cohort panels. Finally, we demonstrate the utility of the TPBWT in a brief empirical analysis exploring geographic patterns of haplotype sharing within Mexico. Hierarchical clustering of IBD shared across regions within Mexico reveals geographically structured haplotype sharing and a strong signal of isolation by distance. Our software implementation of the TPBWT is freely available for non-commercial use in the code repository https://github.com/23andMe/phasedibd.

bioinformatics↗

bioRxiv2019

INTERACTION BETWEEN PLOIDY, BREEDING SYSTEM, AND LINEAGE DIVERSIFICATION

If particular traits consistently affect rates of speciation and extinction, broad macroevolutionary patterns can be understood as consequences of selection at high levels of the biological hierarchy. Identifying traits associated with diversification rate differences is complicated by the wide variety of characters under consideration and the statistical challenges of testing for associations from comparative phylogenetic data. Ploidy (diploid vs. polyploid states) and breeding system (self-incompatible vs. self-compatible states) have been repeatedly suggested as possible drivers of differential diversification. We investigate the connections of these traits, including their interaction, to speciation and extinction rates in Solanaceae. We show that the effect of ploidy on diversification can be largely explained by its correlation with breeding system and that additional unknown factors, alongside breeding system, influence diversification rates. These results are largely robust to allowing for diploidization. Finally, we find that the most common evolutionary pathway to polyploidy in Solanaceae occurs via direct breakdown of self-incompatibility by whole genome duplication, rather than indirectly via breakdown followed by polyploidization.

evolutionary biology↗

bioRxiv2019

A Bayesian Approach for Estimating Branch-Specific Speciation and Extinction Rates

Species richness varies considerably among the tree of life which can only be explained by heterogeneous rates of diversification (speciation and extinction). Previous approaches use phylogenetic trees to estimate branch-specific diversification rates. However, all previous approaches disregard diversification-rate shifts on extinct lineages although 99% of species that ever existed are now extinct. Here we describe a lineage-specific birth-death-shift process where lineages, both extant and extinct, may have heterogeneous rates of diversification. To facilitate probability computation we discretize the base distribution on speciation and extinction rates into k rate categories. The fixed number of rate categories allows us to extend the theory of state-dependent speciation and extinction models (e.g., BiSSE and MuSSE) to compute the probability of an observed phylogeny given the set of speciation and extinction rates. To estimate branch-specific diversification rates, we develop two independent and theoretically equivalent approaches: numerical integration with stochastic character mapping and data-augmentation with reversible-jump Markov chain Monte Carlo sampling. We validate the implementation of the two approaches in RevBayes using simulated data and an empirical example study of primates. In the empirical example, we show that estimates of the number of diversification-rate shifts are, unsurprisingly, very sensitive to the choice of prior distribution. Instead, branch-specific diversification rate estimates are less sensitive to the assumed prior distribution on the number of diversification-rate shifts and consistently infer an increased rate of diversification for Old World Monkeys. Additionally, we observe that as few as 10 diversification-rate categories are sufficient to approximate a continuous base distribution on diversification rates. In conclusion, our implementation of the lineage-specific birth-death-shift model in RevBayes provides biologists with a method to estimate branch-specific diversification rates under a mathematically consistent model.

evolutionary biology↗

bioRxiv2018

Retracing the Hawaiian silversword radiation despite phylogenetic, biogeographic, and paleogeographic uncertainty

The Hawaiian silversword alliance (Asteraceae) is an iconic adaptive radiation of 33 species. However, like many island plant lineages, no fossils have been assigned to the clade. As a result, the clades age and diversification rate are not known precisely, making it difficult to test biogeographic hypotheses about the radiation. In lieu of fossils, paleo-geographically structured biogeographic processes may inform species divergence times; for example, an island must first exist for a clade to radiate upon it. We date the silversword clade and test biogeographic hypotheses about its radiation across the Hawaiian Archipelago by modeling interactions between species relationships, molecular evolution, biogeographic scenarios, divergence times, and island origination times using the Bayesian phylogenetic framework, RevBayes. The ancestor of living silverswords most likely colonized the modern Hawaiian Islands once from the mainland approximately 5.1 Ma, with early surviving silversword lineages first appearing approximately 3.5 Ma. In testing the progression rule of island biogeography, we found strong positive evidence of the dispersal process preferring old-to-young directionality, but strong negative evidence for speciation occurring on islands during their young growth phase. This work serves as a general example for how diversification studies benefit from incorporating biogeographic and paleogeographic components.

evolutionary biology↗

bioRxiv2016

Cladogenetic and Anagenetic Models of Chromosome Number Evolution: a Bayesian Model Averaging Approach

Chromosome number is a key feature of the higher-order organization of the genome, and changes in chromosome number play a fundamental role in evolution. Dysploid gains and losses in chromosome number, as well as polyploidization events, may drive reproductive isolation and lineage diversification. The recent development of probabilistic models of chromosome number evolution in the groundbreaking work by Mayrose et al. (2010, ChromEvol) have enabled the inference of ancestral chromosome numbers over molecular phylogenies and generated new interest in studying the role of chromosome changes in evolution. However, the ChromEvol approach assumes all changes occur anagenetically (along branches), and does not model events that are specifically cladogenetic. Cladogenetic changes may be expected if chromosome changes result in reproductive isolation. Here we present a new class of models of chromosome number evolution (called ChromoSSE) that incorporate both anagenetic and cladogenetic change. The ChromoSSE models allow us to determine the mode of chromosome number evolution; is chromosome evolution occurring primarily within lineages, primarily at lineage splitting, or in clade-specific combinations of both? Furthermore, we can estimate the location and timing of possible chromosome speciation events over the phylogeny. We implemented ChromoSSE in a Bayesian statistical framework, specifically in the software RevBayes, to accommodate uncertainty in parameter estimates while leveraging the full power of likelihood based methods. We tested ChromoSSEs accuracy with simulations and re-examined chromosomal evolution in Aristolochia, Carex section Spirostachyae, Helianthus, Mimulus sensu lato (s.l.), and Primula section Aleuritia, finding evidence for clade-specific combinations of anagenetic and cladogenetic dysploid and polyploid modes of chromosome evolution.

evolutionary biology↗