Biology subjects

Hay, A. D.

Publications and source records attributed to Hay, A. D..

3 recordsLinked to original sources

bioRxiv2024

Analysis of 30 chromosome-level Drosophila genome assemblies reveals dynamic evolution of centromeric satellite repeats

The Drosophila genus is ideal for studying genome evolution due to its simple chromosome structure and small genome size, with rearrangements mainly restricted to within chromosome arms. However, work on the rapidly evolving repetitive genomic regions, composed of transposons and tandem repeats, have been hampered by the lack of genus-wide chromosome-level assemblies. Integrating long read genomic sequencing and chromosome capture technology, we produced and annotated 30 chromosome-level genome assemblies within the Drosophila genus. Based on this dataset, we were able to reveal the evolutionary dynamics of genome rearrangements across the Drosophila phylogeny, including the identification of genomic regions that show comparatively high structural stability throughout evolution. Moreover, within the ananassae subgroup, we uncovered the emergence of new chromosome conformations and the rapid expansion of novel satellite DNA sequence families which form large and continuous peri/centromeric domains with higher-order repeat structures that are reminiscent to those observed in the human and Arabidopsis genomes. These chromosome-level genome assemblies present a highly valuable resource for future research, the power of which was demonstrated by our analysis of genome rearrangements and chromosome evolution. In addition, based on our findings, we propose the ananassae subgroup as an ideal model system for studying the evolution of centromere structure.

evolutionary biology↗

bioRxiv2023

Mitotic heritability of DNA methylation at intermediately methylated sites is imprecise

DNA methylation is considered a stable epigenetic mark due to its presumed long-term inheritance through cell divisions. Here, we perform high-throughput bisulfite sequencing on clonally derived cell lines to quantitatively measure mitotic methylation inheritance at the nucleotide level. We find that although DNA methylation is generally faithfully maintained at hypo- and hypermethylated sites, this is not the case at intermediately methylated CpGs. Low fidelity intermediate methylation is interspersed throughout the genome and within genes with no or low transcriptional activity. Moreover, we determine that the probabilistic changes that occur at intermediately methylated sites are due to DNMT1 rather than DNMT3A/3B activity. The observed lack of clonal inheritance at intermediately methylated sites challenges the concept of DNA methylation as a consistently stable epigenetic mark.

genetics↗

bioRxiv2020

Genomic properties of variably methylated retrotransposons in mouse

Transposable elements (TEs) are enriched in cytosine methylation, preventing their mobility within the genome. We previously identified a genome-wide repertoire of candidate intracisternal A particle (IAP) TEs in mice that exhibit inter-individual variability in this methylation (VM-IAPs) with implications for genome function. Here we validate these metastable epialleles and discover a novel class that exhibit tissue specificity (tsVM-IAPs) in addition to those with uniform methylation in all tissues (constitutive- or cVM-IAPs); both types have the potential to regulate genes in cis. Screening for variable methylation at other TEs shows that this phenomenon is largely limited to IAPs, which are amongst the youngest and most active endogenous retroviruses. We identify sequences enriched within cVM-IAPs, but determine that these are not sufficient to confer epigenetic variability. CTCF is enriched at VM-IAPs with binding inversely correlated with DNA methylation. We uncover dynamic physical interactions between cVM-IAPs with low methylation ranges and other genomic loci, suggesting that VM-IAPs have the potential for long-range regulation. Our findings indicate that a recently evolved interplay between genetic sequence, CTCF binding, and DNA methylation at young TEs can result in inter-individual variability in transcriptional outcomes with implications for phenotypic variation.

genetics↗