Genetic diversity, biogeography and the morpho-genetic relationship in extant planktonic foraminifera

Planktonic foraminifera are widely used as proxies for the reconstruction of past ocean conditions, a method that requires exact species classification and knowledge of their ecological adaptations. Species classification traditionally was conducted using morphological characteristics of the calcite shell. The application of genetic approaches on living planktonic foraminifera, however, challenged the classical species concept, by discovering a large number of cryptic species within the morphospecies. The present dissertation aims at establishing a connection between the fossil record and the genetic background of extant species by finding out to what degree morphologically defined species reflect real biological diversity. Molecular genetic techniques in combination with morphometric analyses were used to examine the extent of cryptic diversity in selected morphospecies and its relation to morphological traits. Furthermore, the biogeographic distribution patterns of extant species were analyzed in order to differentiate between species with local adaptations and endemism versus species with global dispersal and gene flow

Genetic diversity, biogeography and the morpho-genetic relationship in extant planktonic forminifera

Planktonic foraminifera are widely used as proxies for the reconstruction of past ocean conditions, a method that requires exact species classification and knowledge of their ecological adaptations. Species classification traditionally was conducted using morphological characteristics of the calcite shell. The application of genetic approaches on living planktonic foraminifera, however, challenged the classical species concept, by discovering a large number of cryptic species within the morphospecies. The present dissertation aims at establishing a connection between the fossil record and the genetic background of extant species by finding out to what degree morphologically defined species reflect real biological diversity. Molecular genetic techniques in combination with morphometric analyses were used to examine the extent of cryptic diversity in selected morphospecies and its relation to morphological traits. Furthermore, the biogeographic distribution patterns of extant species were analyzed in order to differentiate between species with local adaptations and endemism versus species with global dispersal and gene flow

Sedimentary ancient DNA: a new paleogenomic tool for reconstructing the history of marine ecosystems

Sedimentary ancient DNA (sedaDNA) offers a novel retrospective approach to reconstructing the history of marine ecosystems over geological timescales. Until now, the biological proxies used to reconstruct paleoceanographic and paleoecological conditions were limited to organisms whose remains are preserved in the fossil record. The development of ancient DNA analysis techniques substantially expands the range of studied taxa, providing a holistic overview of past biodiversity. Future development of marine sedaDNA research is expected to dramatically improve our understanding of how the marine biota responded to changing environmental conditions. However, as an emerging approach, marine sedaDNA holds many challenges, and its ability to recover reliable past biodiversity information needs to be carefully assessed. This review aims to highlight current advances in marine sedaDNA research and to discuss potential methodological pitfalls and limitations

Arctic Paleoceanography Cruise KH21-234 with R/V Kronprins Haakon

We set sail from Longyearbyen on 30.6.2021 to collect surface sediments, long sediment archives, water and plankton samples. The study area is located north of Svalbard, within the seasonal and permanent sea ice covered Arctic Ocean. We took stations N of Svalbard, near Nordaustlandet, Sophia Basin, Yermak Plateau and on the shelf east of Svalbard. In total, we had 52 stations. We deployed the multicorer at least once at every station and sampled the core tops already onboard. These samples will be included in the Arctic Surface Sediment DNA Database, which we will use to establish new aDNA based sea ice proxies. We recovered gravity cores from 12 stations that can be used to reconstruct the Arctic sea ice history in the Holocene, last glacial and likely also Last Interglacial. We collected ice and water and filtered these for eDNA and biomarkers, and water for tracing the isotope signal of the different water masses in the region (Atlantic Water, Polar Water).publishedVersio

Importance sampling method of correction for multiple testing in affected sib-pair linkage analysis

Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and naïve Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods. The type I error rates for each correction method and the ability of each of the methods to detect loci known to influence trait values were compared. All of the methods considered were conservative with respect to type I error, especially the Bonferroni method. The ability of these methods to detect trait loci was also low. However, this may be partially due to a limitation inherent in our binary trait definitions

Genetic and morphometric evidence for parallel evolution of the Globigerinella calida morphotype

Molecular genetic investigations of the highly abundant extant planktonic foraminifera plexus Globigerinella siphonifera/Globigerinella calida have recently shown this group to be the genetically most diverse one within planktonic foraminifera, separating it into 12 distinct genetic types belonging to three main genetic lineages. Independently, several morphological or physiological variants have been described within the group, but the correlation between the high genetic diversity and the phenotypic variability remains unclear. In this study, we combine genetic data with morphometric analyses of shell shape and porosity of genotyped individuals of the different genetic lineages. Our morphometric measurements suggest a differentiation of three morphotypes within the plexus, two of which possess the elongated chambers described as a typical trait of G. calida. These two morphotypes with elongated chambers are associated with two distinct genetic lineages. The G. calida morphology therefore appears to have evolved twice in parallel. Unexpectedly, we show that the two morphotypes with elongated chambers can be separated from each other by characters seen in the lateral view of their shells. This implies that the taxonomy of the extant members of the genus Globigerinella should be revised. A comparison with the original descriptions and type specimens of members of the genus shows that two genetic types of one major lineage correspond to G. calida. The second group with elongated chambers is associated with a recently diverged genetic type and we propose to reinstate the name Globigerinella radians for this distinct form. The remaining nine of the 12 genetic types correspond to the G. siphonifera morphology, and in the absence of evidence for morphological differentiation, they form a paraphyletic morpho-taxon. Our results highlight the prevalence of parallelism in the evolution of shell morphology in planktonic foraminifera even at the lowest level of relatedness represented by genetic types

Phylogeography of the tropical planktonic foraminifera lineage Globigerinella reveals isolation inconsistent with passive dispersal by ocean currents

Morphologically defined species of marine plankton often harbor a considerable level of cryptic diversity. Since many morphospecies show cosmopolitan distribution, an understanding of biogeographic and evolutionary processes at the level of genetic diversity requires global sampling. We use a database of 387 single-specimen sequences of the SSU rDNA of the planktonic foraminifera Globigerinella as a model to assess the biogeographic and phylogenetic distributions of cryptic diversity in marine microplankton on a global scale. Our data confirm the existence of multiple, well isolated genetic lineages. An analysis of their abundance and distribution indicates that our sampling is likely to approximate the actual total diversity. Unexpectedly, we observe an uneven allocation of cryptic diversity among the phylogenetic lineages. We show that this pattern is neither an artifact of sampling intensity nor a function of lineage age. Instead, we argue that it reflects an ongoing speciation process in one of the three major lineages. Surprisingly, four of the six genetic types in the hyperdiverse lineage are biogeographically restricted to the Indopacific. Their mutual co-occurrence and their hierarchical phylogenetic structure provide no evidence for an origin through sudden habitat fragmentation and their limitation to the Indopacific challenges the view of a global gene flow within the warm-water provinces. This phenomenon shows that passive dispersal is not sufficient to describe the distribution of plankton diversity. Rather, these organisms show differentiated distribution patterns shaped by species interactions and reflecting phylogenetic contingency with unique histories of diversification rates

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival