Biology subjects

Pellow, R.

Publications and source records attributed to Pellow, R..

3 recordsLinked to original sources

bioRxiv2026

T2T genomes of Caenorhabditis nigoni and Caenorhabditis briggsae reveals extensive loss of satellite DNA associated with self-fertilization

The two closely related Caenorhabditis nematode species, C. nigoni and C. briggsae, are commonly used to study the evolution of reproductive modes in animals, with the self-fertile C. briggsae and outcrossing C. nigoni sharing a common ancestor [~]3.5 million years ago. Earlier genomic analyses of these species revealed genome shrinkage associated with selfing and proposed that at least some gene loss can be adaptive. However, the incomplete C. nigoni reference genome limited most comparative analyses to genic regions. Here, we leveraged long-read sequencing to generate a telomere-to-telomere (T2T) assembly for the C. nigoni strain JU1422 and the C. briggsae strain AF16. This new 139Mb C. nigoni genome resolved 57 gaps and 149 unassigned scaffolds from the previous genome assembly. Comparison with the 107Mb T2T C. briggsae genome reveals that the major driver of genome content differences are deletions to satellite DNA arrays, reflecting a loss of 9.6Mb. Interestingly, many of the differences are on the C. nigoni X chromosome, which is >13Mb larger than in the previous assembly. The transition to selfing was thus accompanied by a 37% reduction in the size of the sex chromosome compared to 16-21% shrinkage of the autosomes. We also document a surprising degree of plasticity in the ribosomal DNA, with the X chromosome harboring a second 45S rDNA array that is absent in C. briggsae. Our analysis reveals that obligatory outcrossing may play a major role in the maintenance of satellite DNA arrays.

genomics↗

bioRxiv2025

High-efficiency targeted integration of extrachromosomal arrays in C. elegans using PhiC31 integrase

Extrachromosomal arrays are unique chromosome-like structures created from DNA injected into the C. elegans germline. However, they are unstable unless integrated into a chromosome. Current methods for integration using X-rays or CRISPR can damage DNA and exhibit low efficiency. We demonstrate that the viral integrase PhiC31, which mediates non-mutagenic recombination between short attB and attP sequences, can be used for extremely efficient and targeted integration of arrays. Arrays were integrated by PhIAT (PhiC31-mediated Integration of Arrays of Transgenes) at attB sites on three chromosomes, including at a fluorescent landing pad. Moreover, integrations can be inserted at any arbitrary site in the genome by simultaneously co-injecting Cas9 RNP, an attB repair template, and the DNA components for the array - thereby providing sites on all six chromosomes. Single injections can integrate arrays ranging in size from 1 to 18 megabases. PhIAT makes it practical to study genomes of other organisms in the nematode; one of our strains incorporates 65% of the yeast genome at a single site in the worm genome. PhIAT will accelerate a shift from unstable extrachromosomal arrays to direct integration of arrays in C. elegans.

genetics↗

bioRxiv2024

A wavelet-based approach generates quantitative, scale-free and hierarchical descriptions of 3D genome structures and new biological insights

Eukaryotes fold their genomes within nuclei in three-dimensional space, with coordinated multiscale structures including loops, topologically associating domains (TADs), and higher-order chromosome territories. This 3D organization plays essential roles in gene regulation and development, responses to physiological stress, and disease. However, current methodologies to infer these 3D structures from genomic data have limitations. These include varying outcomes depending on the resolution of the analysis and sequencing depth, qualitative results that hinder statistical comparisons, lack of insight into the frequency of the structures in samples with many genomes, and no direct inference of hierarchical structures. These shortcomings can make it difficult for the rigorous comparison of 3D properties across genomes, between experimental conditions, or species. To address these challenges, we developed a wavelet transform-based method (WaveTAD) that describes the 3D nuclear organization in a resolution-free, probabilistic, and hierarchical manner. WaveTAD generates probabilities that capture the variable frequency within samples and shows increased accuracy and sensitivity compared to current approaches. We applied WaveTAD to multiple datasets from Drosophila, mouse, and humans to illustrate new biological insights that our more sensitive and quantitative approach provides, such as the widespread presence of embryonic 3D organization before zygotic genome activation, the effect of multiple CTCF units on the stability of loops and TADs, and the association between gene expression and TAD structures in COVID-19 patients or sex-specific transcription in Drosophila.

genomics↗