Microsatellite Repeat Instability Fuels Evolution of Embryonic Enhancers in Hawaiian Drosophila

Brittain, Andrew; Stroebele, Elizabeth; Erives, Albert

doi:10.1371/journal.pone.0101177

Cited by 14 publications

(35 citation statements)

References 55 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[29] There are also fine scale differences between Hawaiian Drosophila species with respect to embryonic enhancer elements important in early development. Brittain et al [30] examined these embryonic enhancers in three Hawaiian Drosophilidae -Scaptomyza anomala, D. grimshawi, and D. mimica. These three species of flies are from very diverse Hawaiian taxa.…”

Section: The Hawaiian Drosophila Are Incredibly Diverse Anatomically mentioning

confidence: 99%

See 1 more Smart Citation

Hawaiian Drosophila as an Evolutionary Model Clade: Days of Future Past

O’Grady

DeSalle

2018

BioEssays

View full text Add to dashboard Cite

The Hawaiian Drosophila have been a model system for evolutionary, ecological, and ethological studies since the inception of the Hawaiian Drosophila Project in the 1960s. Here we review the past and present research on this incredible lineage and provide a prospectus for future directions on genomics and microbial interactions. While the number of publications on this group has waxed and waned over the years, we assert that recent systematic, biogeographic, and ecological studies have reinvigorated Hawaiian Drosophila as an evolutionary model system. The characteristics that distinguish good model clades from good model organisms (e.g., Drosophila melanogaster) are somewhat different so we first define what constitutes a good evolutionary model. We argue that the Hawaiian Drosophila possess many desired aspects of a good evolutionary model, describe how this group of geographically isolated flies have been used in the past, and propose some exciting avenues for future evolutionary research on this diverse, dynamic clade of Drosophila.

show abstract

Section: The Hawaiian Drosophila Are Incredibly Diverse Anatomically mentioning

confidence: 99%

“…embryonic enhancer evolution in picture wings; hybrid impact on gene expression; see Brittain et al [30] ; Brill et al [36] 9. What is the role of plasticity?…”

Section: Genomics Will Greatly Enhance Hawaiian Drosophila Researchmentioning

confidence: 99%

Hawaiian Drosophila as an Evolutionary Model Clade: Days of Future Past

O’Grady

DeSalle

2018

BioEssays

View full text Add to dashboard Cite

show abstract

“…The smallest possible scale to ascribe such homology is that of individual nucleotide positions ("site positional homology"). Of course this is possible only in the context of homological inference based on multiple nucleotide positions in a sequence.By studying the function and evolution of regulatory DNA sequences (transcriptional enhancers in Ciona and Drosophila), which are not constrained by rigid, protein-coding, triplet reading frames (Erives et al Brittain et al 2014;Stroebele and Erives 2016), I conclude that site positional homology is incorrectly handled by gapped alignment (GA). GA was originally adopted by necessity in order to compare protein sequences of divergent lengths (Braunitzer's gappy comparisons of α-and β-hemoglobin…”

mentioning

confidence: 99%

“…In retrospect, GA is not designed to model how regulatory nucleotide sequences evolve for the reasons to be explained here. This issue is exacerbated to great extremes in the regulatory DNAs of the speciose Hawaiian Drosophila (Brittain et al 2014;O'Grady and DeSalle 2018). Nonetheless, this issue also is seen for the sequences encoding many important regulator proteins enriched in polyglutamine content and other repeats, including the Notch intracellular domain and sub-units of the Mediator complex (Tóth-Petróczy et al 2008;Fuxreiter et al 2008;Rice et al 2015;Stroebele and Erives 2016;Erives 2017).…”

mentioning

confidence: 99%

“…Heterogeneous mechanisms likely underlie the instability at TRs, including the short microsatellite repeats (MSR, 1-9 bp units) and minisatellites (10-50 bp units) (Ellegren 2000a,b;Legendre et al 2007). Within transcriptional enhancers some of this repeat content is built up of ancient repeats of repeats with dynamic instability (Crocker et al 2010;Brittain et al 2014). I refer to these more complex, fractal-like patterns, which defy simple categorization as direct tandem repeats, as "DNA microfoam", from a contraction of "micro-paralogy" and quantum spacetime foam (Wheeler 1957;Hawking 1978), and as an allusion to a common role for geometrical changes in dimensionality at the smallest scale.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Maximal homology alignment: A new method based on two-dimensional homology

Erives

2019

Preprint

View full text Add to dashboard Cite

Maximal homology alignment is a new biologically-relevant approach to DNA sequence alignment that embraces microparalogy. It departs from the current method of gapped alignment, which uses a simple, binary state model of nucleotide position. In gapped alignment nucleotide positions have either no relationship (1-to-None) or else orthological relationship (1-to-1) with nucleotides in other sequences. Maximal homology alignment, however, allows additional states such as 1-to-Many and Many-to-Many, thus modeling both orthological and paralogical relationships, which together comprise the main homology types. Maximal homology alignment collects dispersed microparalogy into the same alignment columns on multiple rows, and thereby generates a two-dimensional representation of a single sequence. Sequence alignment then proceeds as the alignment of two-dimensional topological objects. The operations of producing and aligning two dimensional auto-alignments motivate a need for tests of two dimensional homological integrity that are both necessary and sufficient. Here, I work out and implement basic principles for computationally handling the two dimensions of positional homology, which are inherent to biological sequences due to replication slippage and related errors. I then show that maximal homology alignment is more suited and more informative than gapped alignment for modeling the evolution of genetic sequences, which harbor large numbers of small insertions and deletions originating as local microparalogy. These results show that both conserved and non-conserved genomic sequences are imbued with a signature of replication slippage that is absent from their random permutations. KEYWORDS dimensionality; DNA microfoam; Drosophila; enhancer DNAs; gapped alignment (GA); maximal homology alignment (MHA); positional homology; replication slippage; tandem repeats S equences of covalently-linked nucleotides and their evolutionary relationships are the basis of gene homology. The smallest possible scale to ascribe such homology is that of individual nucleotide positions ("site positional homology"). Of course this is possible only in the context of homological inference based on multiple nucleotide positions in a sequence.By studying the function and evolution of regulatory DNA sequences (transcriptional enhancers in Ciona and Drosophila), which are not constrained by rigid, protein-coding, triplet reading frames (Erives et al. Brittain et al. 2014;Stroebele and Erives 2016), I conclude that site positional homology is incorrectly handled by gapped alignment (GA). GA was originally adopted by necessity in order to compare protein sequences of divergent lengths (Braunitzer's gappy comparisons of α-and β-hemoglobin

show abstract

Resolving diverse protein–DNA footprints from exonuclease-based ChIP experiments

Biswas

Narlikar

2021

Bioinformatics

View full text Add to dashboard Cite

Motivation High-throughput chromatin immunoprecipitation (ChIP) sequencing-based assays capture genomic regions associated with the profiled transcription factor (TF). ChIP-exo is a modified protocol, which uses lambda exonuclease to digest DNA close to the TF-DNA complex, in order to improve on the positional resolution of the TF-DNA contact. Because the digestion occurs in the 5′–3′ orientation, the protocol produces directional footprints close to the complex, on both sides of the double stranded DNA. Like all ChIP-based methods, ChIP-exo reports a mixture of different regions associated with the TF: those bound directly to the TF as well as via intermediaries. However, the distribution of footprints are likely to be indicative of the complex forming at the DNA. Results We present ExoDiversity, which uses a model-based framework to learn a joint distribution over footprints and motifs, thus resolving the mixture of ChIP-exo footprints into diverse binding modes. It uses no prior motif or TF information and automatically learns the number of different modes from the data. We show its application on a wide range of TFs and organisms/cell-types. Because its goal is to explain the complete set of reported regions, it is able to identify co-factor TF motifs that appear in a small fraction of the dataset. Further, ExoDiversity discovers small nucleotide variations within and outside canonical motifs, which co-occur with variations in footprints, suggesting that the TF-DNA structural configuration at those regions is likely to be different. Finally, we show that detected modes have specific DNA shape features and conservation signals, giving insights into the structure and function of the putative TF-DNA complexes. Availability and implementation The code for ExoDiversity is available on https://github.com/NarlikarLab/exoDIVERSITY. Supplementary information Supplementary data are available at Bioinformatics online.

show abstract

Microsatellite Repeat Instability Fuels Evolution of Embryonic Enhancers in Hawaiian Drosophila

Cited by 14 publications

References 55 publications

Hawaiian Drosophila as an Evolutionary Model Clade: Days of Future Past

Hawaiian Drosophila as an Evolutionary Model Clade: Days of Future Past

Maximal homology alignment: A new method based on two-dimensional homology

Resolving diverse protein–DNA footprints from exonuclease-based ChIP experiments

Contact Info

Product

Resources

About