Heidi E. L. Lischer

University of Bern

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Kentaro K. Shimizu

Kihara Institute for Biological Research

Rie Shimizu‐Inatsugi

University of Zurich

Roman Briskine

University of Zurich

Rémy Bruggmann

University of Bern

Jun Sese

Tokyo Institute of Technology

Rémy Bruggmann

SIB Swiss Institute of Bioinformatics

Christine Grossen

Swiss Federal Institute for Forest, Snow and Landscape Research

Deborah M. Leigh

Swiss Federal Institute for Forest, Snow and Landscape Research

Stephanie C. Talker

University of Bern

Masaomi Hatakeyama

University of Zurich

Cooperative Institutions

University of Zurich

University of Bern

University of Basel

SIB Swiss Institute of Bioinformatics

University Hospital of Basel

ETH Zurich

University of Fribourg

University of Toronto

Institut de Biologia Evolutiva

Cornell University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Fine-scale ecological and transcriptomic data reveal niche differentiation of an allopolyploid from diploid parents in Cardamine

bioRxiv (Cold Spring Harbor Laboratory) (2019)

Reiko Akiyama Jianqiang Sun Masaomi Hatakeyama Heidi E. L. Lischer Roman Briskine

Abstract Polyploidization, or whole genome duplication, is one of the major mechanisms of plant speciation. Allopolyploids (species that harbor polyploid genomes originating from hybridization of different diploid species) have been hypothesized to occupy a niche with intermediate, broader, or fluctuating environmental conditions compared with parental diploids. It remains unclear whether empirical data support this hypothesis and whether specialization of expression patterns of the homeologs (paralogous gene copies resulting from allopolyploidization) relates to habitat environments. Here, we studied the ecology and transcriptomics of a wild allopolyploid Cardamine flexuosa and its diploid parents C. hirsuta and C. amara at a fine geographical scale in their native area in Switzerland. We found that the diploid parents favored opposite extremes in terms of soil moisture, soil carbon-to-nitrogen ratios, and light availability. The habitat of the allopolyploid C. flexuosa was broader compared with those of its parental species and overlapped with those of the parents, but not at its extremes. In C. flexuosa , the genes related to water availability were overrepresented among those at both the expression level and the expression ratio of homeolog pairs, which varied among habitat environments. These findings provide empirical evidence for niche differentiation between an allopolyploid and its diploid parents at a fine scale, where both ecological and transcriptomic data indicated water availability to be the key environmental factor for niche differentiation. Significance statement Polyploidization, or whole genome duplication, is common in plants and may contribute to their ecological diversification. However, little is known about the niche differentiation of wild allopolyploids relative to their diploid parents and the gene expression patterns that may underlie such ecological divergence. We detected niche differentiation between the allopolyploid Cardamine flexuosa and its diploid parents C. amara and C. hirsuta along water availability gradient at a fine scale. The ecological differentiation was mirrored by the dynamic control of water availability-related gene expression patterns according to habitat environments. Thus, both ecological and transcriptomic data revealed niche differentiation between an allopolyploid species and its diploid parents.

Polyploid

10.1101/600783

Cite

Citations (4)

Fibronectin Fragments and Inflammation During Canine Intervertebral Disc Disease

Frontiers in Veterinary Science (2020)

M Schmidli Aleksandra Sadowska Iva Cvitaš Benjamin Gantenbein Heidi E. L. Lischer

Background: Canine intervertebral disc disease (IVDD) represents a significant clinical problem in veterinary medicine, with similarities to the human pathology. Host-derived damage-associated molecular patterns like fibronectin fragments (FnF) that develop during tissue dysfunction may be of specific relevance to IVD pathologies by inducing an inflammatory response in resident cells. Aim: This project aimed to determine the presence and pathobiological role of FnF during IVD herniation in dogs, with a focus on inflammation. Methods: Herniated nucleus pulposus (NP) material from five dogs as well as non-herniated adjacent NP material from three dogs was collected during spinal surgery required due to acute IVD herniation. The presence of different types of FnF were determined by Western blot analysis. NP cells isolated from six herniated canine IVDs were then exposed to 30 kDa FnF. NP cell inflammation and catabolism was examined by investigating the expression of IL-1β, IL-6, IL-8 and COX-2, as well as MMP-1 and MMP-3 by qPCR (all targets) and ELISA (IL-6, PGE2). Results: Amongst multiple sized FnF (30, 35, 45 and >170kDa), N-terminal fragments at a size of approximately 30 kDa were most consistently expressed in all five herniated IVDs. Importantly, these fragments were exclusively present in herniated, but not in non-herniated IVDs. Exposure of canine NP cells to 500 nM 30kDa FnF caused a significant upregulation of IL-6 (62.5 ± 79.9, p=0.032) and IL-8 (53.0 ± 75.7, p=0.031) on the gene level, whereas IL-6 protein analysis was inconclusive. Donor-donor variation was observed in response to FnF treatment, whereby this phenomenon was most evident for COX-2, with three donors demonstrating a significant downregulation (0.67 ± 0.03, p=0.003) and three donors showing upregulation (6.9 ± 5.5, p=0.21). Co-treatment with Sparstolonin B, a TRL-2/TRL-4 antagonist, showed no statistical difference to FnF treatment alone in all tested target genes. Conclusion: Given the presence of the 30kDa FnF in canine herniated IVDs and the proinflammatory effect of 30kDa FnF on NP cells, we concluded that the accumulation of FnF may be involved in the pathogenesis of canine IVDD. These results correspond to the findings in humans with IVDD.

Intervertebral Disc

10.3389/fvets.2020.547644

Cite

Citations (9)

Disentangling adaptation from drift in bottlenecked and reintroduced populations of Alpine ibex

Authorea (Authorea) (2021)

Deborah M. Leigh Heidi E. L. Lischer Frédéric Guillaume Christine Grossen Torsten Günther

Identifying local adaptation in bottlenecked species is essential for conservation management. Selection detection methods have an important role in species management plans, assessments of adaptive capacity, and looking for responses to climate change. Yet, the allele frequency changes exploited in selection detection methods are similar to those caused by the strong neutral genetic drift expected during a bottleneck. Consequently, it is often unclear what accuracy selection detection methods have across bottlenecked populations. In this study, simulations were used to explore if signals of selection could be confidently distinguished from genetic drift across 23 bottlenecked and reintroduced populations of Alpine ibex (Capra ibex). The meticulously recorded demographic history of the Alpine ibex was used to generate comprehensive simulated SNP data. The simulated SNPs were then used to benchmark the confidence we could place in outliers identified in empirical Alpine ibex SNP data. Within the simulated dataset, the false positive rates were high for all selection detection methods but fell substantially when two or more methods were combined. True positive rates were consistently low and became negligible with increased stringency. Despite finding many outlier loci in the empirical Alpine ibex SNPs, none could be distinguished from genetic drift-driven false positives. Unfortunately, the low true positive rate also prevents the exclusion of recent local adaptation within the Alpine ibex. The baselines and stringent approach outlined here should be applied to other bottlenecked species to ensure the risk of false positive, or negative, signals of selection are accounted for in conservation management plans.

Genetic drift

10.22541/au.161446597.74243424/v1

Cite

Citations (3)

Assessing Metagenomic Signals Recovered from Lyuba, a 42,000-Year-Old Permafrost-Preserved Woolly Mammoth Calf

Genes (2018)

Giada Ferrari Heidi E. L. Lischer Judith Neukamm Enrique Rayo Nicole Borel

The reconstruction of ancient metagenomes from archaeological material, and their implication in human health and evolution, is one of the most recent advances in paleomicrobiological studies. However, as for all ancient DNA (aDNA) studies, environmental and laboratory contamination need to be specifically addressed. Here we attempted to reconstruct the tissue-specific metagenomes of a 42,000-year-old, permafrost-preserved woolly mammoth calf through shotgun high-throughput sequencing. We analyzed the taxonomic composition of all tissue samples together with environmental and non-template experimental controls and compared them to metagenomes obtained from permafrost and elephant fecal samples. Preliminary results suggested the presence of tissue-specific metagenomic signals. We identified bacterial species that were present in only one experimental sample, absent from controls, and consistent with the nature of the samples. However, we failed to further authenticate any of these signals and conclude that, even when experimental samples are distinct from environmental and laboratory controls, this does not necessarily indicate endogenous presence of ancient host-associated microbiomic signals.

Ancient DNA

Environmental DNA

Mammoth

10.3390/genes9090436

Cite

Citations (5)

Ignoring Heterozygous Sites Biases Phylogenomic Estimates of Divergence Times: Implications for the Evolutionary History of Microtus Voles

Molecular Biology and Evolution (2013)

Heidi E. L. Lischer Laurent Excoffier Gerald Heckel

Phylogenetic reconstruction of the evolutionary history of closely related organisms may be difficult because of the presence of unsorted lineages and of a relatively high proportion of heterozygous sites that are usually not handled well by phylogenetic programs. Genomic data may provide enough fixed polymorphisms to resolve phylogenetic trees, but the diploid nature of sequence data remains analytically challenging. Here, we performed a phylogenomic reconstruction of the evolutionary history of the common vole (Microtus arvalis) with a focus on the influence of heterozygosity on the estimation of intraspecific divergence times. We used genome-wide sequence information from 15 voles distributed across the European range. We provide a novel approach to integrate heterozygous information in existing phylogenetic programs by repeated random haplotype sampling from sequences with multiple unphased heterozygous sites. We evaluated the impact of the use of full, partial, or no heterozygous information for tree reconstructions on divergence time estimates. All results consistently showed four deep and strongly supported evolutionary lineages in the vole data. These lineages undergoing divergence processes split only at the end or after the last glacial maximum based on calibration with radiocarbon-dated paleontological material. However, the incorporation of information from heterozygous sites had a significant impact on absolute and relative branch length estimations. Ignoring heterozygous information led to an overestimation of divergence times between the evolutionary lineages of M. arvalis. We conclude that the exclusion of heterozygous sites from evolutionary analyses may cause biased and misleading divergence time estimates in closely related taxa.

Divergence (linguistics)

Coalescent theory

10.1093/molbev/mst271

Cite

Citations (92)

New genomic features of the polled intersex syndrome variant in goats unraveled by long‐read whole‐genome sequencing

Animal Genetics (2020)

Rebecca Simon Heidi E. L. Lischer Aldona Pieńkowska-Schelling Irene Keller Irene M. Häfliger

In domestic goats, the polled intersex syndrome (PIS) refers to XX female-to-male sex reversal associated with the absence of horn growth (polled). The causal variant was previously reported as a 11.7 kb deletion at approximately 129 Mb on chromosome 1 that affects the transcription of both FOXL2 and several long non-coding RNAs. In the meantime the presence of different versions of the PIS deletion was postulated and trials to establish genetic testing with the existing molecular genetic information failed. Therefore, we revisited this variant by long-read whole-genome sequencing of two genetically female (XX) goats, a PIS-affected and a horned control. This revealed the presence of a more complex structural variant consisting of a deletion with a total length of 10 159 bp and an inversely inserted approximately 480 kb-sized duplicated segment of a region located approximately 21 Mb further downstream on chromosome 1 containing two genes, KCNJ15 and ERG. Publicly available short-read whole-genome sequencing data, Sanger sequencing of the breakpoints and FISH using BAC clones corresponding to both involved genome regions confirmed this structural variant. A diagnostic PCR was developed for simultaneous genotyping of carriers for this variant and determination of their genetic sex. We showed that the variant allele was present in all 334 genotyped polled goats of diverse breeds and that all analyzed 15 PIS-affected XX goats were homozygous. Our findings enable for the first time a precise genetic diagnosis for polledness and PIS in goats and add a further genomic feature to the complexity of the PIS phenomenon.

Sanger sequencing

Bacterial artificial chromosome

10.1111/age.12918

Cite

Citations (23)

Batch effects in a multiyear sequencing study: False biological trends due to changes in read lengths

Molecular Ecology Resources (2018)

Deborah M. Leigh Heidi E. L. Lischer Christine Grossen Lukas F. Keller

High-throughput sequencing is a powerful tool, but suffers biases and errors that must be accounted for to prevent false biological conclusions. Such errors include batch effects; technical errors only present in subsets of data due to procedural changes within a study. If overlooked and multiple batches of data are combined, spurious biological signals can arise, particularly if batches of data are correlated with biological variables. Batch effects can be minimized through randomization of sample groups across batches. However, in long-term or multiyear studies where data are added incrementally, full randomization is impossible, and batch effects may be a common feature. Here, we present a case study where false signals of selection were detected due to a batch effect in a multiyear study of Alpine ibex (Capra ibex). The batch effect arose because sequencing read length changed over the course of the project and populations were added incrementally to the study, resulting in nonrandom distributions of populations across read lengths. The differences in read length caused small misalignments in a subset of the data, leading to false variant alleles and thus false SNPs. Pronounced allele frequency differences between populations arose at these SNPs because of the correlation between read length and population. This created highly statistically significant, but biologically spurious, signals of selection and false associations between allele frequencies and the environment. We highlight the risk of batch effects and discuss strategies to reduce the impacts of batch effects in multiyear high-throughput sequencing studies.

10.1111/1755-0998.12779

Cite

Citations (40)

Using historic fixed soft tissues for retrospective genomic analyses: a methodological evaluation

The 86th Annual Meeting of the American Association of Physical Anthropologists, New Orleans (2017)

Giada Ferrari Heidi E. L. Lischer Gülfirde Akgül Frank Rühli Abigail Bouwman

Source

Cite

Citations (0)

Author response for "Transcriptomic profiling of bovine blood dendritic cells and monocytes following toll‐like receptor stimulation"

G.Tuba Barut Heidi E. L. Lischer Rémy Bruggmann Artur Summerfield Stephanie C. Talker

Profiling (computer programming)