Biology subjects

Pederson, S.

Publications and source records attributed to Pederson, S..

3 recordsLinked to original sources

bioRxiv2018

Transposable elements and gene expression during the evolution of amniotes

BackgroundTransposable elements (TEs) are primarily responsible for the changes in genome sequences that occur over time within and between species. TEs themselves evolve, with clade specific LTR/ERV, LINEs and SINEs responsible for the bulk of species specific genomic features. Because TEs can contain regulatory motifs, they can be exapted as regulators of gene expression. While TE insertions can provide evolutionary novelty for the regulation of gene expression, their overall impact on the evolution of gene expression is unclear. Previous investigators have shown that tissue specific gene expression in amniotes is more similar across species than within species, supporting the existence of conserved developmental gene regulation. In order to understand how species specific TE insertions might affect the evolution/conservation of gene expression, we have looked at the association of gene expression in six tissues with TE insertions in six representative amniote genomes (human, opossum, platypus, anole lizard, bearded dragon and chicken).\n\nResultsWe have used a novel bootstrapping approach to minimise the conflation of effects of repeat types on gene expression. We compared the expression of orthologs containing different types of recent TE insertions to orthologs that contained older TE insertions and found significant differences in gene expression associated with TE insertions. Likewise, we compared the expression of non-ortholog genes containing different types of recent TE insertions to non-orthologs with older TE insertions and found significant differences in gene expression associated with TE insertions. As expected TEs were associated with species-specific changes in gene expression, but the magnitude and direction of change of expression changes were unexpected. Overall, orthologs containing clade specific TEs were associated with lower gene expression, while in non-orthologs, non clade-specific TEs were associated with higher gene expression. Exceptions were SINE elements in human and chicken, which had an opposite association with gene expression compared to other species.\n\nConclusionsOur observed species-specific associations of TEs with gene expression support a role for TEs in speciation/response to selection by species. TEs do not exhibit consistent associations with gene expression and observed associations can vary depending on the age of TE insertions. Based on these observations, it would be prudent to refrain from extrapolating these and previously reported associations to distantly related species.

evolutionary biology↗

bioRxiv2018

Accelerated brain aging towards transcriptional inversion in a zebrafish model of familial Alzheimer’s disease

Alzheimers disease (AD) develops silently over decades. We cannot easily access and analyse pre-symptomatic brains, so the earliest molecular changes that initiate AD remain unclear. Previously, we demonstrated that the genes mutated in early-onset, dominantly-inherited familial forms of AD (fAD) are evolving particularly rapidly in mice and rats. Fortunately, some non-mammalian vertebrates such as the zebrafish preserve fAD-relevant transcript isoforms of the PRESENILIN (PSEN1 and PSEN2) genes that these rodents have lost. Zebrafish are powerful vertebrate genetic models for many human diseases, but no genetic model of fAD in zebrafish currently exists. We edited the zebrafish genome to model the unique, protein-truncating fAD mutation of human PSEN2, K115fs. Analysing the brain transcriptome and proteome of young (6-month-old) and aged, infertile (24-month-old) wild type and heterozygous fAD-like mutant female sibling zebrafish supports accelerated brain aging and increased glucocorticoid signalling in young fAD-like fish, leading to a transcriptional inversion into glucocorticoid resistance and vast changes in biological pathways in aged, infertile fAD-like fish. Notably, one of these changes involving microglia-associated immune responses regulated by the ETS transcription factor family is preserved between our zebrafish fAD model and human early-onset AD. Importantly, these changes occur before obvious histopathology and likely in the absence of A{beta}. Our results support the contributions of early metabolic and oxidative stresses to immune and stress responses favouring AD pathogenesis and highlight the value of our fAD-like zebrafish genetic model for elucidating early changes in the brain that promote AD pathogenesis. The success of our approach has important implications for future modelling of AD.

bioinformatics↗

bioRxiv2017

Genome-Wide Analysis Of Repetitive Elements Associated With Gene Regulation

Nearly half of the human genome is made up of transposable elements (TEs) and there is evidence that TEs are involved in gene regulation. Here, we have integrated publicly available genomic, epigenetic and transcriptomic data to investigate this in a genome-wide manner. A bootstrapping statistical method was applied to minimize the confounder effects from different repeat types. Our results show that although most TE classes are primarily associated with reduced gene expression, Alu elements are associated with up regulated gene expression. Furthermore, Alu elements had the highest probability of any TE class of contributing to regulatory regions of any type defined by chromatin state. This suggests a general model where clade specific SINEs may contribute more to gene regulation than ancient/ancestral TEs. Finally, non-coding regions were found to have a high probability of TE content within regulatory sequences, most notably in repressors. Our exhaustive analysis has extended and updated our understanding of TEs in terms of their global impact on gene regulation, and suggests that the most recently derived types of TEs, i.e. clade or species specific SINES, have the greatest overall impact on gene regulation.

genomics↗