Biology subjects

Kofler, R.

Publications and source records attributed to Kofler, R..

25 records · Page 2Linked to original sources

bioRxiv2019

piRNA clusters need a minimum size to control transposable element invasions

piRNA clusters are thought to repress transposable element activity in mammals and invertebrates. Here we show that a simple population genetics model reveals a constraint on the size of piRNA clusters: the total size of the piRNA clusters of an organism ought to exceed 0.2% of a genome. Larger piRNA clusters accounting for up to 3% of the genome may be necessary when populations are small, transposition rates are high and TE insertions recessive. If piRNA clusters are too small the load of deleterious TE insertions accumulating during a TE invasion may drive populations extinct before an effective piRNA based defence against the TE can be established. Our finding is solely based on three well supported assumptions: i) TEs multiply withing genomes, ii) TEs are mostly deleterious and iii) piRNA clusters act as transposons traps, where a single insertion in a cluster silences all TE copies in trans. Interestingly, piRNA clusters of some species meet our minimum size requirements while clusters of other species dont. Species with small piRNA clusters, such as humans and mice, may experience severe fitness reductions during invasions of novel TEs, possibly even threatening the persistence of some populations. This work also raises the important question of how piRNA clusters evolve. We propose that the size of piRNA clusters may be at an equilibrium between evolutionary forces that act to expand and contract piRNA clusters.

evolutionary biology↗

bioRxiv2019

Reconstructing the invasion route of DNA transposons using extant population samples

Reconstructing invasion routes of transposable elements (TEs), so far, required capturing an ongoing invasion with population samples from different geographic regions and time points. Here, we propose a more accessible approach. Abundantly occurring internal deletions of DNA transposons allow to trace the direction as well as the path of an invasion, even hundreds of generations after the spread of a TE. We validated this hypothesis with computer simulations and by accurately reproducing the route of the P-element invasion in Drosophila melanogaster. Finally, we used our method to shed light on the controversial hobo invasion in D. melanogaster. Our approach solely requires sequenced samples from extant populations and sequences of TEs of interest. Hence, DNA transposons in a wide range of model and non-model organisms may be analyzed. Our approach will further our understanding of TE dynamics, migration patterns, and the ecology of species.

evolutionary biology↗

bioRxiv2019

Benchmarking software tools for detecting and quantifying selection in Evolve and Resequencing studies

The combination of experimental evolution with whole genome re-sequencing of pooled individuals, also called Evolve and Resequence (E&R) is a powerful approach to study selection processes and to infer the architecture of adaptive variation. Given the large potential of this method, a range of software tools were developed to identify selected SNPs and to measure their selection coefficients. In this benchmarking study, we are comparing 15 test statistics implemented in 10 software tools using three different scenarios. We demonstrate that the power of the methods differs among the scenarios, but some consistently outperform others. LRT-1, which takes advantage of time series data consistently performed best for all three scenarios. Nevertheless, the CMH test, which requires only two time points had almost the same performance. This benchmark study will not only facilitate the analysis of already existing data, but also affect the design of future data collections.

evolutionary biology↗

bioRxiv2019

Optimizing the power to identify the genetic basis of complex traits with Evolve and Resequence studies

Evolve and Resequence (E&R) studies are frequently used to dissect the genetic basis of quantitative traits. By subjecting a population to truncating selection for several generations and estimating the allele frequency differences between selected and non-selected populations using Next Generation Sequencing, the loci contributing to the selected trait may be identified. The role of different parameters, such as, the population size or the number of replicate populations have been examined in previous works. However, the influence of the selection regime, i.e. the strength of truncating selection during the experiment, remains little explored. Using whole genome, individual based forward simulations of E&R studies, we found that the power to identify the causative alleles may be maximized by gradually increasing the strength of truncating selection during the experiment. Notably, such an optimal selection regime comes at no or little additional cost in terms of sequencing effort and experimental time. Interestingly, we also found that a selection regime which optimizes the power to identify the causative loci is not necessarily identical to a regime that maximizes the phenotypic response. Finally, our simulations suggest that an E&R study with an optimized selection regime may have a higher power to identify the genetic basis of quantitative traits than a GWAS, highlighting that E&R is a powerful approach for finding the loci underlying complex traits.

evolutionary biology↗

bioRxiv2018

Dynamics of transposable element invasions with piRNA clusters

In mammals and in invertebrates the proliferation of a newly invading transposable element (TE) is thought to be stopped by a random insertion of one member of the invading TE family into a piRNA cluster. This view is known as the trap model. Here we explore the dynamics of TE invasions under the trap model using large-scale computer simulations. We found that piRNA clusters confer a substantial benefit, effectively preventing extinction of host populations from an uncontrollable proliferation of deleterious TEs. We show that TE invasions under the trap model consists of three distinct phases: first the TE rapidly amplifies within the population, next TE proliferation is stopped by segregating cluster insertions and finally the TE is permanently inactivated by fixation of a cluster insertion. Suppression by segregating cluster insertions is unstable and bursts of TE activity may yet occur. The transpositon rate and the population size mostly influence the length of the phases but not the amount of TEs accumulating during an invasion. Solely the size of piRNA clusters was identified as a major factor influencing TE abundance. Investigating the impact of different cluster architectures we found that a single non-recombining cluster (e.g. the somatic cluster flamenco in Drosophila) is more efficient in stopping invasions than clusters distributed over several chromosomes (e.g germline cluster in Drosophila). With the somatic architecture fewer TEs accumulate during an invasion and fewer cluster insertions are required to stop the TE. The inefficiency of the germline architecture stems from recombination among cluster sites which makes it necessary that each diploid carries, on the average, four cluster insertions, such that most individuals will end up with at least one cluster insertion. Surprisingly we found that negative selection in a model with piRNA clusters can lead to a novel equilibrium state, where TE copy numbers remain stable despite only some individuals in a population carrying a cluster insertion. Finally when applying our approach to real data from Drosophila melanogaster we found that the trap model reasonably well accounts for the abundance of germline TEs but not of somatic TEs. The abundance of somatic TEs, such as gypsy, is much lower than expected.

evolutionary biology↗

bioRxiv2018

Polygenic adaptation fuels genetic redundancy in Drosophila

The genetic architecture of adaptive traits is of key importance to predict evolutionary responses. Most adaptive traits are polygenic - i.e. result from selection on a large number of genetic loci - but most molecularly characterized traits have a simple genetic basis. This discrepancy is best explained by the difficulty in detecting small allele frequency changes across many contributing loci. To resolve this, we use laboratory natural selection, a framework that is powerful enough to detect signatures for selective sweeps and polygenic adaptation. We exposed 10 replicates of a Drosophila simulans population to a new temperature regime and uncovered a polygenic architecture of an adaptive trait with high genetic redundancy among adaptive alleles. We observed convergent phenotypic responses, e.g. fitness, metabolic rate and fat content, and a strong polygenic response (99 selected alleles; mean s=0.061). However, each of these selected alleles increased in frequency only in a subset of the evolving replicates. Our results show that natural D. simulans populations harbor a vast reservoir of adaptive variation facilitating rapid evolutionary responses. The observed genetic redundancy potentiates this genotypic variation through multiple genetic pathways leading to phenotypic convergence. This key property of adaptive alleles requires the modification of testing strategies in natural populations beyond the search for convergence on the molecular level.

evolutionary biology↗

bioRxiv2016

Chironomus riparius (Diptera) genome sequencing reveals the impact of minisatellite transposable elements on population divergence

Active transposable elements (TEs) may result in divergent genomic insertion and abundance patterns among conspecific populations. Upon secondary contact, such divergent genetic backgrounds can theoretically give rise to classical Dobzhansky-Muller incompatibilities (DMI), a way how TEs can contribute to the evolution of endogenous genetic barriers and eventually population divergence. We investigated whether differential TE activity created endogenous selection pressures among conspecific populations of the non-biting midge Chironomus riparius, focussing on a Chironomus-specific TE, the minisatellite-like Cla-element, whose activity is associated with speciation in the genus. Using an improved and annotated draft genome for a genomic study with five natural C. riparius populations, we found highly population-specific TE insertion patterns with many private insertions. A highly significant correlation of pairwise population FST from genome-wide SNPs with the FST estimated from TEs suggests drift as the major force driving TE population differentiation. However, the significantly higher Cla-element FST level due to a high proportion of differentially fixed Cla-element insertions indicates that segregating, i.e. heterozygous insertions are selected against. With reciprocal crossing experiments and fluorescent in-situ hybridisation of Cla-elements to polytene chromosomes, we documented phenotypic effects on female fertility and chromosomal mispairings that might be linked to DMI in hybrids. We propose that the inferred negative selection on heterozygous Cla-element insertions causes endogenous genetic barriers and therefore acts as DMI among C. riparius populations. The intrinsic genomic turnover exerted by TEs, thus, may have a direct impact on population divergence that is operationally different from drift and local adaptation.

genomics↗