Biology subjects

Josefa González

Publications and source records attributed to Josefa González.

3 recordsLinked to original sources

bioRxiv2016

Stress affects the epigenetic marks added by Bari-Jheh: a natural insertion associated with two adaptive phenotypes in Drosophila

Transposable elements are emerging as an important source of cis-acting regulatory sequences and epigenetic marks that could influence gene expression. However, few studies have dissected the role of specific transposable element insertions on epigenetic gene regulation. Bari-Jheh is a natural transposon that mediates resistance to oxidative stress by adding cis-regulatory sequences that affect expression of nearby genes. In this work, we integrated publicly available data with chromatin immunoprecipitation experiments to get a more comprehensive picture of Bari-Jheh molecular effects. We showed that Bari-Jheh was enriched for H3K9me3 in nonstress conditions, and for H3K9me3, H3K4me3 and H3K27me3 in oxidative stress conditions, which is consistent with expression changes in adjacent genes. We further showed that under oxidative stress conditions, H3K4me3 and H3K9me3 spread to the promoter region of Jheh1 gene. Finally, another insertion of the Bari1 family was associated with increased H3K27me3 in oxidative stress conditions suggesting that Bari1 histone marks are copy-specific. We concluded that besides adding cis-regulatory sequences, Bari-Jheh influences gene expression by affecting the local chromatin state.

Evolutionary Biology↗

bioRxiv2014

Exploring the phenotypic space and the evolutionary history of a natural mutation in Drosophila melanogaster

A major challenge of modern Biology is elucidating the functional consequences of natural mutations. While we have a good understanding of the effects of lab-induced mutations on the molecular- and organismal-level phenotypes, the study of natural mutations has lagged behind. In this work, we explore the phenotypic space and the evolutionary history of a previously identified adaptive transposable element insertion. We first combined several tests that capture different signatures of selection to show that there is evidence of positive selection in the regions flanking FBti0019386 insertion. We then explored several phenotypes related to known phenotypic effects of nearby genes, and having plausible connections to fitness variation in nature. We found that flies with FBti0019386 insertion had a shorter developmental time and were more sensitive to stress, which are likely to be the adaptive effect and the cost of selection of this mutation, respectively. Interestingly, these phenotypic effects are not consistent with a role of FBti0019386 in temperate adaptation as has been previously suggested. Indeed, a global analysis of the population frequency of FBti0019386 showed that clinal frequency patterns are found in North America and Australia but not in Europe. Finally, we showed that FBti0019386 is associated with down-regulation of sra most likely because it induces the formation of heterochromatin by recruiting HP1a protein. Overall, our integrative approach allowed us to shed light on the evolutionary history, the relevant fitness effects and the likely molecular mechanisms of an adaptive mutation and highlights the complexity of natural genetic variants.

Evolutionary Biology↗

bioRxiv2014

T-lex2: genotyping, frequency estimation and re-annotation of transposable elements using single or pooled next-generation sequencing data

Transposable elements (TEs) are the most active, diverse and ancient component in a broad range of genomes. As such, a complete understanding of genome function and evolution cannot be achieved without a thorough understanding of TE impact and biology. However, in-depth analyses of TEs still represent a challenge due to the repetitive nature of these genomic entities. In this work, we present a broadly applicable and flexible tool: T-lex2. T-lex2 is the only available software that allows routine,automatic, and accurate genotyping of individual TE insertions and estimation of their population frequencies both using individual strain and pooled next-generation sequencing (NGS) data. Furthermore, T-lex2 also assesses the quality of the calls allowing the identification of miss-annotated TEs and providing the necessary information to re-annotate them. Although we tested the fidelity of T-lex2 using the high quality Drosophila melanogaster genome, the flexible and customizable design of T-lex2 allows running it in any genome and for any type of TE insertion. Overall, T-lex2 represents a significant improvement in our ability to analyze the contribution of TEs to genome function and evolution as well as learning about the biology of TEs. T-lex2 is freely available online at http://petrov.stanford.edu/cgi-bin/Tlex.html.

Bioinformatics↗