Insights into the Evolution of Cotton Diploids and Polyploids from Whole-Genome Re-sequencing

Understanding the composition, evolution, and function of the Gossypium hirsutum (cotton) genome is complicated by the joint presence of two genomes in its nucleus (AT and DT genomes). These two genomes were derived from progenitor A-genome and D-genome diploids involved in ancestral allopolyploidization. To better understand the allopolyploid genome, we re-sequenced the genomes of extant diploid relatives that contain the A1 (Gossypium herbaceum), A2 (Gossypium arboreum), or D5 (Gossypium raimondii) genomes. We conducted a comparative analysis using deep re-sequencing of multiple accessions of each diploid species and identified 24 million SNPs between the A-diploid and D-diploid genomes. These analyses facilitated the construction of a robust index of conserved SNPs between the A-genomes and D-genomes at all detected polymorphic loci. This index is widely applicable for read mapping efforts of other diploid and allopolyploid Gossypium accessions. Further analysis also revealed locations of putative duplications and deletions in the A-genome relative to the D-genome reference sequence. The approximately 25,400 deleted regions included more than 50% deletion of 978 genes, including many involved with starch synthesis. In the polyploid genome, we also detected 1,472 conversion events between homoeologous chromosomes, including events that overlapped 113 genes. Continued characterization of the Gossypium genomes will further enhance our ability to manipulate fiber and agronomic production of cotton

Diversity of 534 pairs of duplicated genes in allotetraploid Gossypium hirsutum

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The Cytonuclear Dimension of Allopolyploid Evolution: An Example from Cotton Using Rubisco

International audienceDuring allopolyploid speciation, two divergent nuclear genomes merge, yet only one (usually the maternal) of the two sets of progenitor organellar genomes is maintained. Rubisco (1,5-bisphosphate carboxylase/oxygenase) is composed of nuclear-encoded small subunits (SSUs) and plastome-encoded large subunits (LSUs), providing an ideal system to explore the evolutionary process of cytonuclear accommodation. Here, we take initial steps in this direction, using Gossypium allopolyploids as our model. SSU copies from divergent (5-10 My) progenitor diploids (''A'' and ''D'' genomes) were combined at the time of polyploid formation 1-2 Ma, with the LSU encoded by the maternal A-genome parent. LSU genes from A- and D-genome diploids and AD-genome allopolyploids were sequenced, revealing several nonsynonymous substitutions and suggesting the possibility of differential selection on the nuclear-encoded rbcS partner following allopolyploid formation. Sequence data for the rbcS gene family revealed nonreciprocal homoeologous recombination between A- and D-rbcS homoeologs in all polyploid species but not in a synthetic intergenomic F1 hybrid, demonstrating ''gene conversion'' during allopolyploid evolution. All progenitor rbcS genes are retained and expressed in the five extant allopolyploid species, but analysis of the leaf transcriptome showed that A-homoeologs are preferentially expressed in both the allopolyploid and hybrid, consistent with the maternal origin of rbcL. Although rbcS genes from both progenitor genomes are expressed, some appear to have experienced mutations that may represent cytonuclear coevolution

Unequal accumulation of nucleotide diversity in the two co-resident genomes of allopolyploid cotton The correlation of DNA methylation and homoeologous gene expression in cotton pearl

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Unequal accumulation of nucleotide diversity in the two co-resident genomes of allopolyploid cotton The correlation of DNA methylation and homoeologous gene expression in cotton pearl

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Unequal Accumulation Of Nucleotide Diversity In The Two Co-Resident Genomes Of Allopolyploid Cotton

Rates of molecular evolution are highly variable within and among genes and among lineages. The forces responsible for this variation include a suite of internal genomic mechanisms (e.g., recombinational environment, repair efficiency) and external population level phenomena (e.g., selection, effective population size). A promising model for disentangling intrinsic and extrinsic forces are allopolyploid plants, which combine two (or more) set of homoeologous genes in a single nucleus and in the same ecological context. Thus, the null hypothesis may be tested that homoeologs will accumulate nucleotide diversity at equivalent rates in a set of populations within a species. Here we test this hypothesis using Gossypium hirsutum (cotton), a natural allopolyploid derived from the merger, 1-2 million years ago (MYA) of progenitor diploid genomes (A and D), which diverged from a common ancestor ~5-10 million years ago. Homoeologous chromosomes in the allopolyploid (AT and DtT remain highly similar to those of their diploid orthologs, with high synteny and colinearity. Using sequence capture and 454 sequencing, we screened 40 diverse G. hirsutum accessions, targeting exonic regions in ~400 homoeologous gene pairs. Analyzed sequences included approximately twice the target space, due to recovery of introns and flanking UTRs. Nucleotide diversity levels in G. hirsutum are low, consistent with earlier indications. Notwithstanding this low level of overall diversity, preliminary analyses suggest that diversity is higher in the At genome than the Dt genome, genome-wide. This enhanced diversity may reflect differences related to the two-fold difference in progenitor genome size. Our results demonstrate that genic environment plays a key role in the genesis of genetic novelty, and how allopolyploidy can create novel allelic combinations with the potential for adaptive traits

Unequal Accumulation Of Nucleotide Diversity In The Two Co-Resident Genomes Of Allopolyploid Cotton

Rates of molecular evolution are highly variable within and among genes and among lineages. The forces responsible for this variation include a suite of internal genomic mechanisms (e.g., recombinational environment, repair efficiency) and external population level phenomena (e.g., selection, effective population size). A promising model for disentangling intrinsic and extrinsic forces are allopolyploid plants, which combine two (or more) set of homoeologous genes in a single nucleus and in the same ecological context. Thus, the null hypothesis may be tested that homoeologs will accumulate nucleotide diversity at equivalent rates in a set of populations within a species. Here we test this hypothesis using Gossypium hirsutum (cotton), a natural allopolyploid derived from the merger, 1-2 million years ago (MYA) of progenitor diploid genomes (A and D), which diverged from a common ancestor ~5-10 million years ago. Homoeologous chromosomes in the allopolyploid (AT and DtT remain highly similar to those of their diploid orthologs, with high synteny and colinearity. Using sequence capture and 454 sequencing, we screened 40 diverse G. hirsutum accessions, targeting exonic regions in ~400 homoeologous gene pairs. Analyzed sequences included approximately twice the target space, due to recovery of introns and flanking UTRs. Nucleotide diversity levels in G. hirsutum are low, consistent with earlier indications. Notwithstanding this low level of overall diversity, preliminary analyses suggest that diversity is higher in the At genome than the Dt genome, genome-wide. This enhanced diversity may reflect differences related to the two-fold difference in progenitor genome size. Our results demonstrate that genic environment plays a key role in the genesis of genetic novelty, and how allopolyploidy can create novel allelic combinations with the potential for adaptive traits

Insights into the Evolution of Cotton Diploids and Polyploids from Whole-Genome Re-sequencing

Understanding the composition, evolution, and function of the Gossypium hirsutum (cotton) genome is complicated by the joint presence of two genomes in its nucleus (AT and DT genomes). These two genomes were derived from progenitor A-genome and D-genome diploids involved in ancestral allopolyploidization. To better understand the allopolyploid genome, we re-sequenced the genomes of extant diploid relatives that contain the A1 (Gossypium herbaceum), A2 (Gossypium arboreum), or D5 (Gossypium raimondii) genomes. We conducted a comparative analysis using deep re-sequencing of multiple accessions of each diploid species and identified 24 million SNPs between the A-diploid and D-diploid genomes. These analyses facilitated the construction of a robust index of conserved SNPs between the A-genomes and D-genomes at all detected polymorphic loci. This index is widely applicable for read mapping efforts of other diploid and allopolyploid Gossypium accessions. Further analysis also revealed locations of putative duplications and deletions in the A-genome relative to the D-genome reference sequence. The approximately 25,400 deleted regions included more than 50% deletion of 978 genes, including many involved with starch synthesis. In the polyploid genome, we also detected 1,472 conversion events between homoeologous chromosomes, including events that overlapped 113 genes. Continued characterization of the Gossypium genomes will further enhance our ability to manipulate fiber and agronomic production of cotton.This article is from G3 3 (2013): 1809, doi:10.1534/g3.113.007229. Posted with permission.</p

Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In the primary analysis of the global phase II ELIANA trial (ClinicalTrials.gov identifier: NCT02435849 ), tisagenlecleucel provided an overall remission rate of 81% in pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), with 59% of responders remaining relapse-free at 12 months. Here, we report an update on efficacy, safety, and patient-reported quality of life in 79 pediatric and young adult patients with R/R B-ALL following a median follow-up of 38.8 months. The overall remission rate was 82%. The median event-free survival was 24 months, and the median overall survival was not reached. Event-free survival was 44% (95% CI, 31 to 57) and overall survival was 63% (95% CI, 51 to 73) at 3 years overall (most events occur within the first 2 years). The estimated 3-year relapse-free survival with and without censoring for subsequent therapy was 52% (95% CI, 37 to 66) and 48% (95% CI, 34 to 60), respectively. No new or unexpected long-term adverse events were reported. Grade 3/4 adverse events were reported in 29% of patients &gt; 1 year after infusion; grade 3/4 infection rate did not increase &gt; 1 year after infusion. Patients reported improvements in quality of life up to 36 months after infusion. These findings demonstrate favorable long-term safety and suggest tisagenlecleucel as a curative treatment option for heavily pretreated pediatric and young adult patients with R/R B-ALL. </jats:p