Title: Using all Gene Families Vastly Expands Data Available for Phylogenomic Inference
Abstract Traditionally, single-copy orthologs have been the gold standard in phylogenomics. Most phylogenomic studies identify putative single-copy orthologs using clustering approaches and retain families with a single sequence per species. This limits the amount of data available by excluding larger families. Recent advances have suggested several ways to include data from larger families. For instance, tree-based decomposition methods facilitate the extraction of orthologs from large families. Additionally, several methods for species tree inference are robust to the inclusion of paralogs and could use all of the data from larger families. Here, we explore the effects of using all families for phylogenetic inference by examining relationships among 26 primate species in detail and by analyzing five additional data sets. We compare single-copy families, orthologs extracted using tree-based decomposition approaches, and all families with all data. We explore several species tree inference methods, finding that identical trees are returned across nearly all subsets of the data and methods for primates. The relationships among Platyrrhini remain contentious; however, the species tree inference method matters more than the subset of data used. Using data from larger gene families drastically increases the number of genes available and leads to consistent estimates of branch lengths, nodal certainty and concordance, and inferences of introgression in primates. For the other data sets, topological inferences are consistent whether single-copy families or orthologs extracted using decomposition approaches are analyzed. Using larger gene families is a promising approach to include more data in phylogenomics without sacrificing accuracy, at least when high-quality genomes are available. more »« less
Abstract Phylogenetic inference from genome-wide data (phylogenomics) has revolutionized the study of evolution because it enables accounting for discordance among evolutionary histories across the genome. To this end, summary methods have been developed to allow accurate and scalable inference of species trees from gene trees. However, most of these methods, including the widely used ASTRAL, can only handle single-copy gene trees and do not attempt to model gene duplication and gene loss. As a result, most phylogenomic studies have focused on single-copy genes and have discarded large parts of the data. Here, we first propose a measure of quartet similarity between single-copy and multicopy trees that accounts for orthology and paralogy. We then introduce a method called ASTRAL-Pro (ASTRAL for PaRalogs and Orthologs) to find the species tree that optimizes our quartet similarity measure using dynamic programing. By studying its performance on an extensive collection of simulated data sets and on real data sets, we show that ASTRAL-Pro is more accurate than alternative methods.
Sanderson, Michael J.; Búrquez, Alberto; Copetti, Dario; McMahon, Michelle M.; Zeng, Yichao; Wojciechowski, Martin F.; Solis-Lemus, ed., Claudia(
, Systematic Biology)
Abstract
Reconstructing accurate historical relationships within a species poses numerous challenges, not least in many plant groups in which gene flow is high enough to extend well beyond species boundaries. Nonetheless, the extent of tree-like history within a species is an empirical question on which it is now possible to bring large amounts of genome sequence to bear. We assess phylogenetic structure across the geographic range of the saguaro cactus, an emblematic member of Cactaceae, a clade known for extensive hybridization and porous species boundaries. Using 200 Gb of whole genome resequencing data from 20 individuals sampled from 10 localities, we assembled two data sets comprising 150,000 biallelic single nucleotide polymorphisms (SNPs) from protein coding sequences. From these, we inferred within-species trees and evaluated their significance and robustness using five qualitatively different inference methods. Despite the low sequence diversity, large census population sizes, and presence of wide-ranging pollen and seed dispersal agents, phylogenetic trees were well resolved and highly consistent across both data sets and all methods. We inferred that the most likely root, based on marginal likelihood comparisons, is to the east and south of the region of highest genetic diversity, which lies along the coast of the Gulf of California in Sonora, Mexico. Together with striking decreases in marginal likelihood found to the north, this supports hypotheses that saguaro’s current range reflects postglacial expansion from the refugia in the south of its range. We conclude with observations about practical and theoretical issues raised by phylogenomic data sets within species, in which SNP-based methods must be used rather than gene tree methods that are widely used when sequence divergence is higher. These include computational scalability, inference of gene flow, and proper assessment of statistical support in the presence of linkage effects. [Phylogenomics; phylogeography; rooting; Sonoran Desert.]
Yan, Zhi; Smith, Megan L; Du, Peng; Hahn, Matthew W; Nakhleh, Luay(
, Systematic Biology)
Kubatko, Laura
(Ed.)
Abstract Many recent phylogenetic methods have focused on accurately inferring species trees when there is gene tree discordance due to incomplete lineage sorting (ILS). For almost all of these methods, and for phylogenetic methods in general, the data for each locus are assumed to consist of orthologous, single-copy sequences. Loci that are present in more than a single copy in any of the studied genomes are excluded from the data. These steps greatly reduce the number of loci available for analysis. The question we seek to answer in this study is: what happens if one runs such species tree inference methods on data where paralogy is present, in addition to or without ILS being present? Through simulation studies and analyses of two large biological data sets, we show that running such methods on data with paralogs can still provide accurate results. We use multiple different methods, some of which are based directly on the multispecies coalescent model, and some of which have been proven to be statistically consistent under it. We also treat the paralogous loci in multiple ways: from explicitly denoting them as paralogs, to randomly selecting one copy per species. In all cases, the inferred species trees are as accurate as equivalent analyses using single-copy orthologs. Our results have significant implications for the use of ILS-aware phylogenomic analyses, demonstrating that they do not have to be restricted to single-copy loci. This will greatly increase the amount of data that can be used for phylogenetic inference.[Gene duplication and loss; incomplete lineage sorting; multispecies coalescent; orthology; paralogy.]
Yuan, Hao; Jiang, Jiamei; Jiménez, Francisco Agustín; Hoberg, Eric P.; Cook, Joseph A.; Galbreath, Kurt E.; Li, Chenhong(
, Molecular Ecology Resources)
Abstract
The Cyclophyllidea is the most diverse order of tapeworms, encompassing species that infect all classes of terrestrial tetrapods including humans and domesticated animals. Available phylogenetic reconstructions based either on morphology or molecular data lack the resolution to allow scientists to either propose a solid taxonomy or infer evolutionary associations. Molecular markers available for the Cyclophyllidea mostly include ribosomalDNAand mitochondrial loci. In this study, we identified 3641 single‐copy nuclear coding loci by comparing the genomes ofHymenolepis microstoma,Echinococcus granulosusandTaenia solium. We designedRNAbaits based on the sequence ofH. microstoma, and applied target enrichment and Illumina sequencing to test the utility of those baits to recover loci useful for phylogenetic analyses. We capturedDNAfrom five species of tapeworms representing two families of cyclophyllideans. We obtained an average of 3284 (90%) of the targets from the test samples and then used captured sequences (2 181 361 bp in total; fragment size ranging from 301 to 6969 bp) to reconstruct a phylogeny for the five test species plus the three species for which genomic data are available. The results were consistent with the current consensus regarding cyclophyllidean relationships. To assess the potential for our method to yield informative genetic variation at intraspecific scales, we extracted 14 074 single nucleotide polymorphisms (SNPs) from alignments of fourArostrilepis macrocirrosaand twoA. cookiand successfully inferred their relationships. The results showed that our target gene tools yield data sets that provide robust inferences at a range of taxonomic scales in the Cyclophyllidea.
Hoyt, Savannah J.; Storer, Jessica M.; Hartley, Gabrielle A.; Grady, Patrick G.; Gershman, Ariel; de Lima, Leonardo G.; Limouse, Charles; Halabian, Reza; Wojenski, Luke; Rodriguez, Matias; et al(
, Science)
INTRODUCTION Transposable elements (TEs), repeat expansions, and repeat-mediated structural rearrangements play key roles in chromosome structure and species evolution, contribute to human genetic variation, and substantially influence human health through copy number variants, structural variants, insertions, deletions, and alterations to gene transcription and splicing. Despite their formative role in genome stability, repetitive regions have been relegated to gaps and collapsed regions in human genome reference GRCh38 owing to the technological limitations during its development. The lack of linear sequence in these regions, particularly in centromeres, resulted in the inability to fully explore the repeat content of the human genome in the context of both local and regional chromosomal environments. RATIONALE Long-read sequencing supported the complete, telomere-to-telomere (T2T) assembly of the pseudo-haploid human cell line CHM13. This resource affords a genome-scale assessment of all human repetitive sequences, including TEs and previously unknown repeats and satellites, both within and outside of gaps and collapsed regions. Additionally, a complete genome enables the opportunity to explore the epigenetic and transcriptional profiles of these elements that are fundamental to our understanding of chromosome structure, function, and evolution. Comparative analyses reveal modes of repeat divergence, evolution, and expansion or contraction with locus-level resolution. RESULTS We implemented a comprehensive repeat annotation workflow using previously known human repeats and de novo repeat modeling followed by manual curation, including assessing overlaps with gene annotations, segmental duplications, tandem repeats, and annotated repeats. Using this method, we developed an updated catalog of human repetitive sequences and refined previous repeat annotations. We discovered 43 previously unknown repeats and repeat variants and characterized 19 complex, composite repetitive structures, which often carry genes, across T2T-CHM13. Using precision nuclear run-on sequencing (PRO-seq) and CpG methylated sites generated from Oxford Nanopore Technologies long-read sequencing data, we assessed RNA polymerase engagement across retroelements genome-wide, revealing correlations between nascent transcription, sequence divergence, CpG density, and methylation. These analyses were extended to evaluate RNA polymerase occupancy for all repeats, including high-density satellite repeats that reside in previously inaccessible centromeric regions of all human chromosomes. Moreover, using both mapping-dependent and mapping-independent approaches across early developmental stages and a complete cell cycle time series, we found that engaged RNA polymerase across satellites is low; in contrast, TE transcription is abundant and serves as a boundary for changes in CpG methylation and centromere substructure. Together, these data reveal the dynamic relationship between transcriptionally active retroelement subclasses and DNA methylation, as well as potential mechanisms for the derivation and evolution of new repeat families and composite elements. Focusing on the emerging T2T-level assembly of the HG002 X chromosome, we reveal that a high level of repeat variation likely exists across the human population, including composite element copy numbers that affect gene copy number. Additionally, we highlight the impact of repeats on the structural diversity of the genome, revealing repeat expansions with extreme copy number differences between humans and primates while also providing high-confidence annotations of retroelement transduction events. CONCLUSION The comprehensive repeat annotations and updated repeat models described herein serve as a resource for expanding the compendium of human genome sequences and reveal the impact of specific repeats on the human genome. In developing this resource, we provide a methodological framework for assessing repeat variation within and between human genomes. The exhaustive assessment of the transcriptional landscape of repeats, at both the genome scale and locally, such as within centromeres, sets the stage for functional studies to disentangle the role transcription plays in the mechanisms essential for genome stability and chromosome segregation. Finally, our work demonstrates the need to increase efforts toward achieving T2T-level assemblies for nonhuman primates and other species to fully understand the complexity and impact of repeat-derived genomic innovations that define primate lineages, including humans. Telomere-to-telomere assembly of CHM13 supports repeat annotations and discoveries. The human reference T2T-CHM13 filled gaps and corrected collapsed regions (triangles) in GRCh38. Combining long read–based methylation calls, PRO-seq, and multilevel computational methods, we provide a compendium of human repeats, define retroelement expression and methylation profiles, and delineate locus-specific sites of nascent transcription genome-wide, including previously inaccessible centromeres. SINE, short interspersed element; SVA, SINE–variable number tandem repeat– Alu ; LINE, long interspersed element; LTR, long terminal repeat; TSS, transcription start site; pA, xxxxxxxxxxxxxxxx.
Smith, Megan L., Vanderpool, Dan, and Hahn, Matthew W. Using all Gene Families Vastly Expands Data Available for Phylogenomic Inference. Retrieved from https://par.nsf.gov/biblio/10355332. Molecular Biology and Evolution 39.6 Web. doi:10.1093/molbev/msac112.
Smith, Megan L., Vanderpool, Dan, & Hahn, Matthew W. Using all Gene Families Vastly Expands Data Available for Phylogenomic Inference. Molecular Biology and Evolution, 39 (6). Retrieved from https://par.nsf.gov/biblio/10355332. https://doi.org/10.1093/molbev/msac112
@article{osti_10355332,
place = {Country unknown/Code not available},
title = {Using all Gene Families Vastly Expands Data Available for Phylogenomic Inference},
url = {https://par.nsf.gov/biblio/10355332},
DOI = {10.1093/molbev/msac112},
abstractNote = {Abstract Traditionally, single-copy orthologs have been the gold standard in phylogenomics. Most phylogenomic studies identify putative single-copy orthologs using clustering approaches and retain families with a single sequence per species. This limits the amount of data available by excluding larger families. Recent advances have suggested several ways to include data from larger families. For instance, tree-based decomposition methods facilitate the extraction of orthologs from large families. Additionally, several methods for species tree inference are robust to the inclusion of paralogs and could use all of the data from larger families. Here, we explore the effects of using all families for phylogenetic inference by examining relationships among 26 primate species in detail and by analyzing five additional data sets. We compare single-copy families, orthologs extracted using tree-based decomposition approaches, and all families with all data. We explore several species tree inference methods, finding that identical trees are returned across nearly all subsets of the data and methods for primates. The relationships among Platyrrhini remain contentious; however, the species tree inference method matters more than the subset of data used. Using data from larger gene families drastically increases the number of genes available and leads to consistent estimates of branch lengths, nodal certainty and concordance, and inferences of introgression in primates. For the other data sets, topological inferences are consistent whether single-copy families or orthologs extracted using decomposition approaches are analyzed. Using larger gene families is a promising approach to include more data in phylogenomics without sacrificing accuracy, at least when high-quality genomes are available.},
journal = {Molecular Biology and Evolution},
volume = {39},
number = {6},
author = {Smith, Megan L. and Vanderpool, Dan and Hahn, Matthew W.},
editor = {Townsend, Jeffrey}
}
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