@article{qi_an_hall_di_blischak_mckibben_hao_conant_pires_barker_2021, title={Genes derived from ancient polyploidy have higher genetic diversity and are associated with domestication in Brassica rapa}, volume={230}, ISSN={["1469-8137"]}, DOI={10.1111/nph.17194}, abstractNote={Summary


Many crops are polyploid or have a polyploid ancestry. Recent phylogenetic analyses have found that polyploidy often preceded the domestication of crop plants. One explanation for this observation is that increased genetic diversity following polyploidy may have been important during the strong artificial selection that occurs during domestication.

In order to test the connection between domestication and polyploidy, we identified and examined candidate genes associated with the domestication of the diverse crop varieties of Brassica rapa. Like all ‘diploid’ flowering plants, B. rapa has a diploidized paleopolyploid genome and experienced many rounds of whole genome duplication (WGD). We analyzed transcriptome data of more than 100 cultivated B. rapa accessions.

Using a combination of approaches, we identified > 3000 candidate genes associated with the domestication of four major B. rapa crop varieties. Consistent with our expectation, we found that the candidate genes were significantly enriched with genes derived from the Brassiceae mesohexaploidy. We also observed that paleologs were significantly more diverse than non‐paleologs.

Our analyses find evidence for that genetic diversity derived from ancient polyploidy played a key role in the domestication of B. rapa and provide support for its importance in the success of modern agriculture.

}, number={1}, journal={NEW PHYTOLOGIST}, author={Qi, Xinshuai and An, Hong and Hall, Tara E. and Di, Chenlu and Blischak, Paul D. and McKibben, Michael T. W. and Hao, Yue and Conant, Gavin C. and Pires, J. Chris and Barker, Michael S.}, year={2021}, month={Apr}, pages={372–386} }
 @article{hao_mabry_edger_freeling_zheng_jin_vanburen_colle_an_abrahams_et al._2021, title={The contributions from the progenitor genomes of the mesopolyploid Brassiceae are evolutionarily distinct but functionally compatible}, volume={31}, ISSN={["1549-5469"]}, DOI={10.1101/gr.270033.120}, abstractNote={The members of the tribe Brassiceae share a whole-genome triplication (WGT), and one proposed model for its formation is a two-step pair of hybridizations producing hexaploid descendants. However, evidence for this model is incomplete, and the evolutionary and functional constraints that drove evolution after the hexaploidy are even less understood. Here, we report a new genome sequence of Crambe hispanica, a species sister to most sequenced Brassiceae. Using this new genome and three others that share the hexaploidy, we traced the history of gene loss after the WGT using the Polyploidy Orthology Inference Tool (POInT). We confirm the two-step formation model and infer that there was a significant temporal gap between those two allopolyploidizations, with about a third of the gene losses from the first two subgenomes occurring before the arrival of the third. We also, for the 90,000 individual genes in our study, make parental subgenome assignments, inferring, with measured uncertainty, from which of the progenitor genomes of the allohexaploidy each gene derives. We further show that each subgenome has a statistically distinguishable rate of homoeolog losses. There is little indication of functional distinction between the three subgenomes: the individual subgenomes show no patterns of functional enrichment, no excess of shared protein–protein or metabolic interactions between their members, and no biases in their likelihood of having experienced a recent selective sweep. We propose a “mix and match” model of allopolyploidy, in which subgenome origin drives homoeolog loss propensities but where genes from different subgenomes function together without difficulty.}, number={5}, journal={GENOME RESEARCH}, author={Hao, Yue and Mabry, Makenzie E. and Edger, Patrick P. and Freeling, Michael and Zheng, Chunfang and Jin, Lingling and VanBuren, Robert and Colle, Marivi and An, Hong and Abrahams, R. Shawn and et al.}, year={2021}, month={May}, pages={799–810} }
 @article{hao_lee_baraboo_burch_maurer_somarelli_conant_2020, title={Baby Genomics: Tracing the Evolutionary Changes That Gave Rise to Placentation}, volume={12}, ISSN={["1759-6653"]}, DOI={10.1093/gbe/evaa026}, abstractNote={Abstract
               It has long been challenging to uncover the molecular mechanisms behind striking morphological innovations such as mammalian pregnancy. We studied the power of a robust comparative orthology pipeline based on gene synteny to address such problems. We inferred orthology relations between human genes and genes from each of 43 other vertebrate genomes, resulting in ∼18,000 orthologous pairs for each genome comparison. By identifying genes that first appear coincident with origin of the placental mammals, we hypothesized that we would define a subset of the genome enriched for genes that played a role in placental evolution. We thus pinpointed orthologs that appeared before and after the divergence of eutherian mammals from marsupials. Reinforcing previous work, we found instead that much of the genetic toolkit of mammalian pregnancy evolved through the repurposing of preexisting genes to new roles. These genes acquired regulatory controls for their novel roles from a group of regulatory genes, many of which did in fact originate at the appearance of the eutherians. Thus, orthologs appearing at the origin of the eutherians are enriched in functions such as transcriptional regulation by Krüppel-associated box-zinc-finger proteins, innate immune responses, keratinization, and the melanoma-associated antigen protein class. Because the cellular mechanisms of invasive placentae are similar to those of metastatic cancers, we then used our orthology inferences to explore the association between placenta invasion and cancer metastasis. Again echoing previous work, we find that genes that are phylogenetically older are more likely to be implicated in cancer development.}, number={3}, journal={GENOME BIOLOGY AND EVOLUTION}, author={Hao, Yue and Lee, Hyuk Jin and Baraboo, Michael and Burch, Katherine and Maurer, Taylor and Somarelli, Jason A. and Conant, Gavin C.}, year={2020}, month={Mar}, pages={35–47} }
 @article{schoonmaker_hao_bird_conant_2020, title={A Single, Shared Triploidy in Three Species of Parasitic Nematodes}, volume={10}, ISSN={["2160-1836"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85077664460&partnerID=MN8TOARS}, DOI={10.1534/g3.119.400650}, abstractNote={Abstract
               The root-knot nematodes of the genus Meloidogyne are important and damaging parasites capable of infecting most flowering plants. Within this genus, several species of the Meloidogyne incognita group show evidence of paleopolyploidy in their genomes. We used our software tool POInT, the Polyploidy Orthology Inference Tool, to phylogenetically model the gene losses that followed that polyploidy. These models, and simulations based on them, show that three of these species (M. incognita, M. arenaria and M. javanica) descend from a single common hybridization event that yielded triplicated genomes with three distinguishable subgenomes. While one of the three subgenomes shows elevated gene loss rates relative to the other two, this subgenome does not show elevated sequence divergence. In all three species, ancestral loci where two of the three gene copies have been lost are less likely to have orthologs in Caenorhabditis elegans that are lethal when knocked down than are ancestral loci with surviving duplicate copies.}, number={1}, journal={G3-GENES GENOMES GENETICS}, author={Schoonmaker, Ashley and Hao, Yue and Bird, David McK. and Conant, Gavin C.}, year={2020}, month={Jan}, pages={225–233} }
 @article{osman_bolding_villalon_kaifer_lorson_tisdale_hao_conant_pires_pellizzoni_et al._2019, title={Functional characterization of SMN evolution in mouse models of SMA}, volume={9}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-019-45822-8}, abstractNote={AbstractSpinal Muscular Atrophy (SMA) is a monogenic neurodegenerative disorder and the leading genetic cause of infantile mortality. While several functions have been ascribed to the SMN (survival motor neuron) protein, their specific contribution to the disease has yet to be fully elucidated. We hypothesized that some, but not all, SMN homologues would rescue the SMA phenotype in mouse models, thereby identifying disease-relevant domains. Using AAV9 to deliver Smn homologs to SMA mice, we identified a conservation threshold that marks the boundary at which homologs can rescue the SMA phenotype. Smn from Danio rerio and Xenopus laevis significantly prevent disease, whereas Smn from Drosophila melanogaster, Caenorhabditis elegans, and Schizosaccharomyces pombe was significantly less efficacious. This phenotypic rescue correlated with correction of RNA processing defects induced by SMN deficiency and neuromuscular junction pathology. Based upon the sequence conservation in the rescuing homologs, a minimal SMN construct was designed consisting of exons 2, 3, and 6, which showed a partial rescue of the SMA phenotype. While a significant extension in survival was observed, the absence of a complete rescue suggests that while the core conserved region is essential, additional sequences contribute to the overall ability of the SMN protein to rescue disease pathology.}, journal={SCIENTIFIC REPORTS}, author={Osman, Erkan Y. and Bolding, Madeline R. and Villalon, Eric and Kaifer, Kevin A. and Lorson, Zachary C. and Tisdale, Sarah and Hao, Yue and Conant, Gavin C. and Pires, J. Chris and Pellizzoni, Livio and et al.}, year={2019}, month={Jul} }
 @article{an_qi_gaynor_hao_gebken_mabry_mcalvay_teakle_conant_barker_et al._2019, title={Transcriptome and organellar sequencing highlights the complex origin and diversification of allotetraploid Brassica napus}, volume={10}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-019-10757-1}, abstractNote={AbstractBrassica napus, an allotetraploid crop, is hypothesized to be a hybrid from unknown varieties of Brassica rapa and Brassica oleracea. Despite the economic importance of B. napus, much is unresolved regarding its phylogenomic relationships, genetic structure, and diversification. Here we conduct a comprehensive study among diverse accessions from 183 B. napus (including rapeseed, rutabaga, and Siberian kale), 112 B. rapa, and 62 B. oleracea and its wild relatives. Using RNA-seq of B. napus accessions, we define the genetic diversity and sub-genome variance of six genetic clusters. Nuclear and organellar phylogenies for B. napus and its progenitors reveal varying patterns of inheritance and post-formation introgression. We discern regions with signatures of selective sweeps and detect 8,187 differentially expressed genes with implications for B. napus diversification. This study highlights the complex origin and evolution of B. napus providing insights that can further facilitate B. napus breeding and germplasm preservation.}, journal={NATURE COMMUNICATIONS}, author={An, Hong and Qi, Xinshuai and Gaynor, Michelle L. and Hao, Yue and Gebken, Sarah C. and Mabry, Makenzie E. and McAlvay, Alex C. and Teakle, Graham R. and Conant, Gavin C. and Barker, Michael S. and et al.}, year={2019}, month={Jun} }
 @article{hao_washburn_rosenthal_nielsen_lyons_edger_pires_conant_2018, title={Patterns of Population Variation in Two Paleopolyploid Eudicot Lineages Suggest That Dosage-Based Selection on Homeologs Is Long-Lived}, volume={10}, ISSN={["1759-6653"]}, DOI={10.1093/gbe/evy061}, abstractNote={Abstract Genes that are inherently subject to strong selective constraints tend to be overretained in duplicate after polyploidy. They also continue to experience similar, but somewhat relaxed, constraints after that polyploidy event. We sought to assess for how long the influence of polyploidy is felt on these genes’ selective pressures. We analyzed two nested polyploidy events in Brassicaceae: the At-α genome duplication that is the most recent polyploidy in the model plant Arabidopsis thaliana and a more recent hexaploidy shared by the genus Brassica and its relatives. By comparing the strength and direction of the natural selection acting at the population and at the species level, we find evidence for continued intensified purifying selection acting on retained duplicates from both polyploidies even down to the present. The constraint observed in preferentially retained genes is not a result of the polyploidy event: the orthologs of such genes experience even stronger constraint in nonpolyploid outgroup genomes. In both the Arabidopsis and Brassica lineages, we further find evidence for segregating mildly deleterious variants, confirming that the population-level data uncover patterns not visible with between-species comparisons. Using the A. thaliana metabolic network, we also explored whether network position was correlated with the measured selective constraint. At both the population and species level, nodes/genes tended to show similar constraints to their neighbors. Our results paint a picture of the long-lived effects of polyploidy on plant genomes, suggesting that even yesterday’s polyploids still have distinct evolutionary trajectories.}, number={3}, journal={GENOME BIOLOGY AND EVOLUTION}, author={Hao, Yue and Washburn, Jacob D. and Rosenthal, Jacob and Nielsen, Brandon and Lyons, Eric and Edger, Patrick P. and Pires, J. Chris and Conant, Gavin C.}, year={2018}, month={Mar}, pages={999–1011} }
 @article{emery_willis_hao_barry_oakgrove_peng_schmutz_lyons_pires_edger_et al._2018, title={Preferential retention of genes from one parental genome after polyploidy illustrates the nature and scope of the genomic conflicts induced by hybridization}, volume={14}, ISSN={["1553-7404"]}, DOI={10.1371/journal.pgen.1007267}, abstractNote={Polyploidy is increasingly seen as a driver of both evolutionary innovation and ecological success. One source of polyploid organisms’ successes may be their origins in the merging and mixing of genomes from two different species (e.g., allopolyploidy). Using POInT (the Polyploid Orthology Inference Tool), we model the resolution of three allopolyploidy events, one from the bakers’ yeast (Saccharomyces cerevisiae), one from the thale cress (Arabidopsis thaliana) and one from grasses including Sorghum bicolor. Analyzing a total of 21 genomes, we assign to every gene a probability for having come from each parental subgenome (i.e., derived from the diploid progenitor species), yielding orthologous segments across all genomes. Our model detects statistically robust evidence for the existence of biased fractionation in all three lineages, whereby genes from one of the two subgenomes were more likely to be lost than those from the other subgenome. We further find that a driver of this pattern of biased losses is the co-retention of genes from the same parental genome that share functional interactions. The pattern of biased fractionation after the Arabidopsis and grass allopolyploid events was surprisingly constant in time, with the same parental genome favored throughout the lineages’ history. In strong contrast, the yeast allopolyploid event shows evidence of biased fractionation only immediately after the event, with balanced gene losses more recently. The rapid loss of functionally associated genes from a single subgenome is difficult to reconcile with the action of genetic drift and suggests that selection may favor the removal of specific duplicates. Coupled to the evidence for continuing, functionally-associated biased fractionation after the A. thaliana At-α event, we suggest that, after allopolyploidy, there are functional conflicts between interacting genes encoded in different subgenomes that are ultimately resolved through preferential duplicate loss.}, number={3}, journal={PLOS GENETICS}, author={Emery, Marianne and Willis, M. Madeline S. and Hao, Yue and Barry, Kerrie and Oakgrove, Khouanchy and Peng, Yi and Schmutz, Jeremy and Lyons, Eric and Pires, J. Chris and Edger, Patrick P. and et al.}, year={2018}, month={Mar} }