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Results for “Genomic selection”

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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Genomic diversifications of five Gossypium allopolyploid species and their impact on cotton improvement

Abstract Polyploidy is an evolutionary innovation for many animals and all flowering plants, but its impact on selection and domestication remains elusive. Here we analyze genome evolution and diversification for all five allopolyploid cotton species, including economically important Upland and Pima cottons. Although these polyploid genomes are conserved in gene content and synteny, they have diversified by subgenomic transposon exchanges that equilibrate genome size, evolutionary rate heterogeneities and positive selection between homoeologs within and among lineages. These differential evolutionary trajectories are accompanied by gene-family diversification and homoeolog expression divergence among polyploid lineages. Selection and domestication drive parallel gene expression similarities in fibers of two cultivated cottons, involving coexpression networks and N 6 -methyladenosine RNA modifications. Furthermore, polyploidy induces recombination suppression, which correlates with altered epigenetic landscapes and can be overcome by wild introgression. These genomic insights will empower efforts to manipulate genetic recombination and modify epigenetic landscapes and target genes for crop improvement.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Testing for the Genomic Footprint of Conflict Between Life Stages in an Angiosperm and Moss Species

Abstract The maintenance of genetic variation by balancing selection is of considerable interest to evolutionary biologists. An important but understudied potential driver of balancing selection is antagonistic pleiotropy between diploid and haploid stages of the plant life cycle. Despite sharing a common genome, sporophytes (2n) and gametophytes (n) may undergo differential or even opposing selection. Theoretical work suggests antagonistic pleiotropy between life stages can generate balancing selection and maintain genetic variation. Despite the potential for far-reaching consequences of gametophytic selection, empirical tests of its pleiotropic effects (neutral, synergistic, or antagonistic) on sporophytes are generally lacking. Here, we examined the population genomic signals of selection across life stages in the angiosperm Rumex hastatulus and the moss Ceratodon purpureus. We compared gene expression between life stages and sexes, combined with neutral diversity statistics and the analysis of the distribution of fitness effects. In contrast to what would be predicted under balancing selection due to antagonistic pleiotropy, we found that unbiased genes between life stages were under stronger purifying selection, likely explained by a predominance of synergistic pleiotropy between life stages and strong purifying selection on broadly expressed genes. In addition, we found that 30% of candidate genes under balancing selection in R. hastatulus were located within inversion polymorphisms. Our findings provide novel insights into the genome-wide characteristics and consequences of plant gametophytic selection.

Evolutionary Biology↗
DOE OSTI2021

ACBD3 is up-regulated in gastric cancer and promotes cell cycle G1-to-S transition in an AKT-dependent manner

Highlights: • ACBD3 is up-regulated in gastric cancer. • ACBD3 regulates cell-cycle of gastric cancer in an AKT-dependent manner. It has been reported that ACBD3 is closely related to the malignant process of cells, but its role in gastric cancer has not been elucidated. This study aims to investigate the expression and function of ACBD3 in human gastric cancer. The Cancer Genome Atlas (TCGA) database were selected to analyze mRNA levels of ACBD3 in gastric cancer tissues and normal gastric epithelial tissues. qPCR and Western blot were conducted to detect the expression of ACBD3 in two normal gastric epithelial cell lines and five gastric cancer cell lines which were cultured in our laboratory. To exclude differences in individual background between different patients, we further detected the expression of ACBD3 in 8 pairs of malignant/non-malignant clinical gastric tissues. Through the establishment of stable cells, in vitro cell experiments and in vivo xenotransplantation models in mice, the role of ACBD3 in the proliferation of gastric cancer cells has been further explored. AKT inhibitors were used to deeply explore the molecular regulation mechanism of ACBD3. The results showed that the elevated ACBD3 in gastric cancer tissue were positively correlated with the clinical grade and prognosis of gastric cancer. In terms of molecular function, we found that ACBD3 can enhance the production and growth of gastric cancer cells. At the same time, the activation of AKT kinase played an important role in ACBD3's promotion of G1-to-S transition. The experiments generally indicate that ACBD3 is expected to become a potential diagnostic molecule or therapeutic target for gastric cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

The Marchantia polymorpha pangenome reveals ancient mechanisms of plant adaptation to the environment

Plant adaptation to terrestrial life started 450 million years ago and has played a major role in the evolution of life on Earth. The genetic mechanisms allowing this adaptation to a diversity of terrestrial constraints have been mostly studied by focusing on flowering plants. Here, we gathered a collection of 133 accessions of the model bryophyte Marchantia polymorpha and studied its intraspecific diversity using selection signature analyses, a genome-environment association study and a pangenome. We identified adaptive features, such as peroxidases or nucleotide-binding and leucine-rich repeats (NLRs), also observed in flowering plants, likely inherited from the first land plants. The M. polymorpha pangenome also harbors lineage-specific accessory genes absent from seed plants. We conclude that different land plant lineages still share many elements from the genetic toolkit evolved by their most recent common ancestor to adapt to the terrestrial habitat, refined by lineage-specific polymorphisms and gene family evolution.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Genetically engineered Foot and Mouth Disease Virus and related proteins, polynucleotides, compositions, methods and systems

Genetically engineered Foot and Mouth Disease Virus (FMDV) and related engineered proteins and polynucleotides, nanolipoprotein particles, compositions, methods and systems are described. The genetically engineered FMDV is modified by the strategic insertion of a protein tag into select regions of the FMDV genome which encode viral proteins that are exposed on the surface of the FMDV viral capsid. The inserted protein tag is displayed as a decoration or attachment on the viral capsid surface.

Rieder, Aida Elizabeth↗
DOE OSTI2023

Genetically engineered foot and mouth disease virus and related proteins, polynucleotides, compositions, methods and systems

Genetically engineered Foot and Mouth Disease Virus (FMDV) and related engineered proteins and polynucleotides, nanolipoprotein particles, compositions, methods and systems are described. The genetically engineered FMDV is modified by the strategic insertion of a protein tag into select regions of the FMDV genome which encode viral proteins that are exposed on the surface of the FMDV viral capsid. The inserted protein tag is displayed as a decoration or attachment on the viral capsid surface.

Rieder, Aida E.↗
DOE OSTI2020

Comparative genetics of Enterococcus faecalis intestinal tissue isolates before and after surgery in a rat model of colon anastomosis

We have recently demonstrated that collagenolytic Enterococcus faecalis plays a key and causative role in the pathogenesis of anastomotic leak, an uncommon but potentially lethal complication characterized by disruption of the intestinal wound following segmental removal of the colon (resection) and its reconnection (anastomosis). Here we hypothesized that comparative genetic analysis of E. faecalis isolates present at the anastomotic wound site before and after surgery would shed insight into the mechanisms by which collagenolytic strains are selected for and predominate at sites of anastomotic disruption. Whole genome optical mapping of four pairs of isolates from rat colonic tissue obtained following surgical resection (herein named "pre-op" isolates) and then 6 days later from the anastomotic site (herein named "post-op" isolates) demonstrated that the isolates with higher collagenolytic activity formed a distinct cluster. In order to perform analysis at a deeper level, a single pair of E. faecalis isolates (16A pre-op and 16A post-op) was selected for whole genome sequencing and assembled using a hybrid assembly algorithm. Comparative genomics demonstrated absence of multiple gene clusters, notably a pathogenicity island in the post-op isolate. No differences were found in the fsr-gelE-sprE genes (EF1817-1822) responsible for regulation and production of collagenolytic activity. Analysis of unique genes among the 16A pre-op and post-op isolates revealed the predominance of transporter systems-related genes in the pre-op isolate and phage-related and hydrolytic enzyme-encoding genes in the post-op isolate. Despite genetic differences observed between pre-op and post-op isolates, the precise genetic determinants responsible for their differential expression of collagenolytic activity remains unknown.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Strong parallel evidence of selection during switchgrass sward establishment in hybrid and lowland ecotypes

Switchgrass sward establishment results in up to 90% seedling mortality. The degree of selection during sward establishment has not been reported using modern genetic methods. Pooled leaf samples were sequenced from replicated swards of 46 half-sib families from two breeding groups (lowland and hybrid) before and through 3 years of stand establishment. Pooled allele frequencies were then assessed using fixation indices (Fst) and an independent data set was used to predict the polygenic impact of establishment selection on two traits (heading date and winter survivorship). Last, the DNA pools were assigned survival rankings to predict the sward survival genomically estimated breeding values within the training data set. Strong and parallel selection occured in both breeding groups. Five genomic regions exceeded the significant threshold of 99.9% in >10 families, indicating consistent selection across families and breeding groups. Polygenic trait predictions determined that establishment selection was partially associated with winter survivorship but resulted in variable heading date alterations. The genomewide variation is consistent with selection for a small number of related parental lines. This study observed strong selection for a small number of hybrid and coastal ecotype individuals which are promising germplasm sources for improved sward survival. This confirms prior reports of sward selection during grassland establishment and highlights the strength of pooled DNA sequencing for survival traits.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Synthase-Selective Exploration of a Tunicate Microbiome by Activity-Guided Single-Cell Genomics

While thousands of environmental metagenomes have been mined for the presence of novel biosynthetic gene clusters, such computational predictions do not provide evidence of their in vivo biosynthetic functionality. Using fluorescent in situ enzyme assay targeting carrier proteins common to polyketide (PKS) and nonribosomal peptide synthetases (NRPS), we applied fluorescence-activated cell sorting to tunicate microbiome to enrich for microbes with active secondary metabolic capabilities. Single-cell genomics uncovered the genetic basis for a wide biosynthetic diversity in the enzyme-active cells and revealed a member of marine Oceanospirillales harboring a novel NRPS gene cluster with high similarity to phylogenetically distant marine and terrestrial bacteria. Interestingly, this synthase belongs to a larger class of siderophore biosynthetic gene clusters commonly associated with pestilence and disease. Furthermore, this demonstrates activity-guided single-cell genomics as a tool to guide novel biosynthetic discovery.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR–Cas9 ribonucleoprotein

Lipid nanoparticle (LNP) delivery of clustered regularly interspaced short palindromic repeat (CRISPR) ribonucleoproteins (RNPs) could enable high-efficiency, low-toxicity and scalable in vivo genome editing if efficacious RNP–LNP complexes can be reliably produced. Here we engineer a thermostable Cas9 from Geobacillus stearothermophilus (GeoCas9) to generate iGeoCas9 variants capable of >100× more genome editing of cells and organs compared with the native GeoCas9 enzyme. Furthermore, iGeoCas9 RNP–LNP complexes edit a variety of cell types and induce homology-directed repair in cells receiving codelivered single-stranded DNA templates. Using tissue-selective LNP formulations, we observe genome-editing levels of 16-37% in the liver and lungs of reporter mice that receive single intravenous injections of iGeoCas9 RNP–LNPs. In addition, iGeoCas9 RNPs complexed to biodegradable LNPs edit the disease-causing SFTPC gene in lung tissue with 19% average efficiency, representing a major improvement over genome-editing levels observed previously using viral or nonviral delivery strategies. These results show that thermostable Cas9 RNP–LNP complexes can expand the therapeutic potential of genome editing.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Quantitative Stable-Isotope Probing (qSIP) with Metagenomics Links Microbial Physiology and Activity to Soil Moisture in Mediterranean-Climate Grassland Ecosystems

The growth and physiology of soil microorganisms, which play vital roles in biogeochemical cycling, are shaped by both current and historical soil environmental conditions. Here, we developed and applied a genome-resolved metagenomic implementation of quantitative stable isotope probing (qSIP) with an H 2 18 O labeling experiment to identify actively growing soil microorganisms and their genomic capacities. qSIP enabled measurement of taxon-specific growth because isotopic incorporation into microbial DNA requires production of new genome copies. We studied three Mediterranean grassland soils across a rainfall gradient to evaluate the hypothesis that historic precipitation levels are an important factor controlling trait selection. We used qSIP-informed genome-resolved metagenomics to resolve the active subset of soil community members and identify their characteristic ecophysiological traits. Higher year-round precipitation levels correlated with higher activity and growth rates of flagellar motile microorganisms. In addition to heavily isotopically labeled bacteria, we identified abundant isotope-labeled phages, suggesting phage-induced cell lysis likely contributed to necromass production at all three sites. Further, there was a positive correlation between phage activity and the activity of putative phage hosts. Contrary to our expectations, the capacity to decompose the diverse complex carbohydrates common in soil organic matter or oxidize methanol and carbon monoxide were broadly distributed across active and inactive bacteria in all three soils, implying that these traits are not highly selected for by historical precipitation.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Adaptive gene loss in the common bean pan-genome during range expansion and domestication

The common bean ( Phaseolus vulgaris L.) is a crucial legume crop and an ideal evolutionary model to study adaptive diversity in wild and domesticated populations. Here, we present a common bean pan-genome based on five high-quality genomes and whole-genome reads representing 339 genotypes. It reveals ~234 Mb of additional sequences containing 6,905 protein-coding genes missing from the reference, constituting 49% of all presence/absence variants (PAVs). More non-synonymous mutations are found in PAVs than core genes, probably reflecting the lower effective population size of PAVs and fitness advantages due to the purging effect of gene loss. Our results suggest pan-genome shrinkage occurred during wild range expansion. Selection signatures provide evidence that partial or complete gene loss was a key adaptive genetic change in common bean populations with major implications for plant adaptation. The pan-genome is a valuable resource for food legume research and breeding for climate change mitigation and sustainable agriculture.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Biomass yield improvement in switchgrass through genomic prediction of flowering time

The seasonal timing of the transition from vegetative to reproductive growth has a major impact on biomass accumulation in switchgrass. Late-flowering switchgrass cultivars produce greater biomass, a critical trait for sustainable bioenergy production. Genomic prediction (GP) may allow rapid selection of late-flowering individuals with reduced time and expense for field evaluations. To evaluate GP, two flowering time traits (heading date and anthesis date) were collected on 1532 genotypes from four breeding populations: Midwest, Gulf, Atlantic, and Hybrid. These were sequenced using genotype-by-sequencing (530,792 single-nucleotide polymorphisms). Predictive ability of single-trait and multi-trait models were evaluated by cross-validation, by prediction of a progeny trial (n = 122), and through prediction of yield performance in a parallel experiment (n = 52). Predictive ability was not improved by sharing information among breeding groups. Overall, multi-trait models provided an advantage during cross-validation, but a smaller advantage during progeny prediction. Within populations, GP resulted in lower per-cycle progress than previously reported field evaluations (3.1 vs. 5.0 day –1 cycle –1 ). However, GP cycles are potentially much faster than field evaluations. When directly predicting biomass yield, the Hybrid training population had a predictive ability of 0.54–0.63. This reinforces the strong linkage between biomass yields in swards and flowering time. Furthermore, these results highlight the value of GP for rapid yield improvement in switchgrass, particularly in a breeding program designed to share information between biomass yield trials and low-cost flowering time evaluations.

09 BIOMASS FUELS↗
DOE OSTI2022

Edaphic controls on genome size and GC content of bacteria in soil microbial communities

Nutrient limitation has been shown to reduce bacterial genome size and influence nucleotide composition; however, much of this work has been conducted in marine systems and the factors which shape soil bacterial genomic traits remain largely unknown. Here, for this work, we determined average genome size, GC content, codon usage, and amino acid content from 398 soil metagenomes across a broad geographic range and used machine-learning to determine the environmental parameters that most strongly explain the distribution of these traits. We found that genomic trait averages were most related to pH, which we suggest is primarily due to the correlation of pH with several environmental parameters, particularly soil carbon content. Low pH soils had higher carbon to nitrogen ratios (C:N) and tended to have communities with lower GC content and larger genomes, potentially a response to increased physiological stress and a requirement for metabolic diversity. Conversely, communities in high pH and low soil C:N had smaller genomes and higher GC content—indicating potential resource driven selection against AT base pairs, which have a higher C:N than GC base pairs. Similarly, we found that nutrient conservation also applied to amino acid stoichiometry, where bacteria in soils with low C:N ratios tended to code for amino acids with lower C:N. Together, these relationships point towards fundamental mechanisms that underpin genome size, and nucleotide and amino acid selection in soil bacteria.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Introgression and persistence of cultivar alleles in wild carrot ( Daucus carota ) populations in the United States

Abstract Premise Cultivated species and their wild relatives often hybridize in the wild, and the hybrids can survive and reproduce in some environments. However, it is unclear whether cultivar alleles are permanently incorporated into the wild genomes or whether they are purged by natural selection. This question is key to accurately assessing the risk of escape and spread of cultivar genes into wild populations. Methods We used genomic data and population genomic methods to study hybridization and introgression between cultivated and wild carrot (Daucus carota) in the United States. We used single nucleotide polymorphisms (SNPs) obtained via genotyping by sequencing for 450 wild individuals from 29 wild georeferenced populations in seven states and 144 cultivars from the United States, Europe, and Asia. Results Cultivated and wild carrot formed two genetically differentiated groups, and evidence of crop–wild admixture was detected in several but not all wild carrot populations in the United States. Two regions were identified where cultivar alleles were present in wild carrots: California and Nantucket Island (Massachusetts). Surprisingly, there was no evidence of introgression in some populations with a long‐known history of sympatry with the crop, suggesting that post‐hybridization barriers might prevent introgression in some areas. Conclusions Our results provide support for the introgression and long‐term persistence of cultivar alleles in wild carrots populations. We thus anticipate that the release of genetically engineered (GE) cultivars would lead to the introduction and spread of GE alleles in wild carrot populations.

Plant Sciences↗
DOE OSTI2023

Addressing the pervasive scarcity of structural annotation in eukaryotic algae

Abstract Despite a continuous increase in algal genome sequencing, structural annotations of most algal genome assemblies remain unavailable. This pervasive scarcity of genome annotation has restricted rigorous investigation of these genomic resources and may have precipitated misleading biological interpretations. However, the annotation process for eukaryotic algal species is often challenging as genomic resources and transcriptomic evidence are not always available. To address this challenge, we benchmark the cutting-edge gene prediction methods that can be generalized for a broad range of non-model eukaryotes. Using the most accurate methods selected based on high-quality algal genomes, we predict structural annotations for 135 unannotated algal genomes. Using previously available genomic data pooled together with new data obtained in this study, we identified the core orthologous genes and the multi-gene phylogeny of eukaryotic algae, including of previously unexplored algal species. This study not only provides a benchmark for the use of structural annotation methods on a variety of non-model eukaryotes, but also compensates for missing data in the current spectrum of algal genomic resources. These results bring us one step closer to the full potential of eukaryotic algal genomics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Targeted genetic manipulation and yeast-like evolutionary genomics in the green alga Auxenochlorella

Auxenochlorella spp. are diploid oleaginous green algae whose streamlined genomes can be readily manipulated by homologous recombination, making them highly amenable to discovery research and bioengineering. Vegetatively diploid organisms experience specific evolutionary phenomena, including allodiploid hybridization, mitotic recombination, loss-of-heterozygosity, and aneuploidy; however, studies of these forces have largely focused on yeasts. Here, we present a telomere-to-telomere phased diploid genome assembly of Auxenochlorella UTEX 250-A (haploid length 22 Mb) and introduce a genetic toolkit for site-specific manipulation of the nuclear genome in multiple strains, featuring several selectable markers, inducible promoters, and fluorescent reporters for protein localization. UTEX 250-A is an allodiploid hybrid of Auxenochlorella protothecoides and Auxenochlorella symbiontica, two species differentiated by extensive chromosomal rearrangements. UTEX 250-A haplotypes are a mosaic of each parental species following mitotic recombination, and two chromosomes are trisomic. Loss-of-heterozygosity events are pervasive across Auxenochlorella and can evolve rapidly in the laboratory. High-quality structural annotation yielded ∼7,500 genes per haplotype. Auxenochlorella have experienced gene family loss and reduction, including core photosynthesis genes, and exhibit periodic adenine and cytosine methylation at promoters and gene bodies, respectively. Approximately 10% of genes, especially those involved in DNA repair and sex, overlap antisense long noncoding RNAs, which may participate in a regulatory mechanism. We demonstrate the utility of Auxenochlorella for fundamental research by knockout of a chlorophyll biosynthesis enzyme, and confirm one trisomy by allele-specific transformation. These results demonstrate the generality of several evolutionary forces associated with vegetative diploidy and provide a foundation for the use of Auxenochlorella as a reference organism.

CHL27↗