Investigating mechanisms of genome expansion in Corydoradinae catfish

The Corydoradinae catfish are a diverse sub-family of neo-tropical catfishes (order Siluriformes) with more than 170 species described to date. One of the most compelling features of this sub-family is the enormous amount of variation in genome size. With species containing between 0.5 pg and 4.8pg of DNA, variation is comparable to that found across the Teleostei as a whole. Previous phylogenetic analysis identified nine distinct lineages within the Corydoradinae, with more basal lineages possessing smaller genomes and with largest genome sizes found in the most derived lineages. To date, nothing is known about the mechanism that drove this genome expansion in the Corydoradinae, though Whole Genome Duplication (WGD) events have been suggested. Here, the incidence of WGD events has been investigated using a Hox gene and a restriction site associated DNA (RAD) sequencing data set. Both data sets identified a major duplication event at the base of the group, with additional duplication events occurring across the family. These duplication events were shown to have led to relaxed purifying selection and increased functional divergence of HoxA13a copies in the Corydoradinae compared with teleosts that have not undergone additional rounds of WGD. The RAD data set confirmed significant genome-wide shifts in duplicate, multi-haplotype regions across the Corydoradinae, and indicates that several species from lineages 6-9 are functionally polyploid, whereas species that underwent earlier WGDs have largely diploidized and are likely paleopolyploids. An increase in paralogous genes was noted, with Gene Ontology suggesting that gene retention in the Corydoradinae mirrors previously described retention in Tetraodon following the fish-specific genome duplication in the Teleostei. Intriguingly, the RAD data also identified a significant expansion of Transposable Elements (TEs), driven by a DNA TE superfamily (Tc1-Mariner). This expansion significantly contributed to the genome size variation, though to a lesser degree than the WGD events identified within this thesis

Whole genome duplication and transposable element proliferation drive genome expansion in Corydoradinae catfishes

Genome size varies significantly across eukaryotic taxa and the largest changes are typically driven by macro-mutations such as whole genome duplications (WGDs) and proliferation of repetitive elements. These two processes may affect the evolutionary potential of lineages by increasing genetic variation and changing gene expression. Here we elucidate the evolutionary history and mechanisms underpinning genome size variation in a species rich group of Neotropical catfishes (Corydoradinae) with extreme variation in genome size - 0.6pg to 4.4 pg per haploid cell. Firstly, genome size was quantified in 65 species and mapped onto a novel fossil-calibrated phylogeny. Two evolutionary shifts in genome size were identified across the tree - the first between 43-49 Mya (95% highest posterior density (HPD) 36.2-68.1 Mya) and the second at ~19 Mya (95% HPD 15.3-30.14 Mya). Secondly, RAD sequencing was used to identify potential WGD events and quantify transposable element abundance in different lineages. Evidence of two lineage scale WGDs were identified across the phylogeny, the first event occurring between 54-66 Mya (95% HPD 42.56-99.5 Mya) and the second at 20-30 Mya (95% HPD 15.3-45 Mya) based on haplotype numbers per contig and between 35-44 Mya (95% HPD 30.29-64.51 Mya) and 20-30 Mya (95% HPD 15.3-45 Mya) based on SNP read ratios. Transposable element abundance increased considerably in parallel with genome size, with a single TE-family (TC1-IS630-Pogo) showing several increases across the Corydoradinae, with the most recent at 20-30 Mya (95% HPD 15.3-45 Mya) and an older event at 35-44 Mya (95% HPD 30.29-64.51 Mya). We identified signals congruent with two WGD duplication events, as well as an increase in TE abundance across different lineages, making the Corydoradinae an excellent model system to study the effects of WGD and TEs on genome and organismal evolution

Transposable element annotation in non‐model species ‐ the benefits of species‐specific repeat libraries using semi‐automated EDTA and DeepTE de novo pipelines

Transposable elements (TEs) are significant genomic components which can be detected either through sequence homology against existing databases or de novo, with the latter potentially reducing the risk of underestimating TE abundance. Here, we describe the semi-automated generation of a de novo TE library using the newly developed EDTA pipeline and DeepTE classifier in a non-model teleost (Corydoras fulleri). Using both genomic and transcriptomic data, we assess this de novo pipeline’s performance across four TE based metrics: (i) abundance, (ii) composition, (iii) fragmentation and (iv) age distributions. We then compare the results to those found when using a curated teleost library (Danio rerio). We identify quantitative differences in these metrics and highlight how TE library choice can have major impacts on TE-based estimates in non-model species

Fluctuating selection on migrant adaptive sodium transporter alleles in coastal Arabidopsis thaliana

Stressors such as soil salinity and dehydration are major constraints on plant growth, causing worldwide crop losses. Compounding these insults, increasing climate volatility requires adaptation to fluctuating conditions. Salinity stress responses are relatively well understood in Arabidopsis thaliana, making this system suited for the rapid molecular dissection of evolutionary mechanisms. In a large-scale genomic analysis of Catalonian A. thaliana, we resequenced 77 individuals from multiple salinity gradients along the coast and integrated these data with 1,135 worldwide A. thaliana genomes for a detailed understanding of the demographic and evolutionary dynamics of naturally evolved salinity tolerance. This revealed that Catalonian varieties adapted to highly fluctuating soil salinity are not Iberian relicts but instead have immigrated to this region more recently. De novo genome assembly of three allelic variants of the high-affinity K+ transporter (HKT1;1) locus resolved structural variation between functionally distinct alleles undergoing fluctuating selection in response to seasonal changes in soil salinity. Plants harboring alleles responsible for low root expression of HKT1;1 and consequently high leaf sodium (HKT1;1HLS) were migrants that have moved specifically into areas where soil sodium levels fluctuate widely due to geography and rainfall variation. We demonstrate that the proportion of plants harboring HKT1;1HLS alleles correlates with soil sodium level over time, HKT1;1HLS-harboring plants are better adapted to intermediate levels of salinity, and the HKT1;1HLS allele clusters with high-sodium accumulator accessions worldwide. Together, our evidence suggests that HKT1;1 is under fluctuating selection in response to climate volatility and is a worldwide determinant in adaptation to saline conditions

Typha (Cattail) Invasion in North American Wetlands: Biology, Regional Problems, Impacts, Ecosystem Services, and Management

Typha is an iconic wetland plant found worldwide. Hybridization and anthropogenic disturbances have resulted in large increases in Typha abundance in wetland ecosystems throughout North America at a cost to native floral and faunal biodiversity. As demonstrated by three regional case studies, Typha is capable of rapidly colonizing habitats and forming monodominant vegetation stands due to traits such as robust size, rapid growth rate, and rhizomatic expansion. Increased nutrient inputs into wetlands and altered hydrologic regimes are among the principal anthropogenic drivers of Typha invasion. Typha is associated with a wide range of negative ecological impacts to wetland and agricultural systems, but also is linked with a variety of ecosystem services such as bioremediation and provisioning of biomass, as well as an assortment of traditional cultural uses. Numerous physical, chemical, and hydrologic control methods are used to manage invasive Typha, but results are inconsistent and multiple methods and repeated treatments often are required. While this review focuses on invasive Typha in North America, the literature cited comes from research on Typha and other invasive species from around the world. As such, many of the underlying concepts in this review are relevant to invasive species in other wetland ecosystems worldwide

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Investigating mechanisms of genome expansion in Corydoradinae catfish

The Corydoradinae catfish are a diverse sub-family of neo-tropical catfishes (order Siluriformes) with more than 170 species described to date. One of the most compelling features of this sub-family is the enormous amount of variation in genome size. With species containing between 0.5 pg and 4.8pg of DNA, variation is comparable to that found across the Teleostei as a whole. Previous phylogenetic analysis identified nine distinct lineages within the Corydoradinae, with more basal lineages possessing smaller genomes and with largest genome sizes found in the most derived lineages. To date, nothing is known about the mechanism that drove this genome expansion in the Corydoradinae, though Whole Genome Duplication (WGD) events have been suggested. Here, the incidence of WGD events has been investigated using a Hox gene and a restriction site associated DNA (RAD) sequencing data set. Both data sets identified a major duplication event at the base of the group, with additional duplication events occurring across the family. These duplication events were shown to have led to relaxed purifying selection and increased functional divergence of HoxA13a copies in the Corydoradinae compared with teleosts that have not undergone additional rounds of WGD. The RAD data set confirmed significant genome-wide shifts in duplicate, multi-haplotype regions across the Corydoradinae, and indicates that several species from lineages 6-9 are functionally polyploid, whereas species that underwent earlier WGDs have largely diploidized and are likely paleopolyploids. An increase in paralogous genes was noted, with Gene Ontology suggesting that gene retention in the Corydoradinae mirrors previously described retention in Tetraodon following the fish-specific genome duplication in the Teleostei. Intriguingly, the RAD data also identified a significant expansion of Transposable Elements (TEs), driven by a DNA TE superfamily (Tc1-Mariner). This expansion significantly contributed to the genome size variation, though to a lesser degree than the WGD events identified within this thesis