Biology subjects

Hodson, C.

Publications and source records attributed to Hodson, C..

3 recordsLinked to original sources

bioRxiv2026

Stronger positive and purifying selection on X-linked genes in a species with paternal genome elimination

The faster-X effect predicts that X chromosomes may evolve more rapidly than autosomes due to selection on expressed recessive alleles. Quantifying the effect empirically usually requires numerous assumptions due to the impact of diplodiploid transmission dynamics, and so the relative contribution of dominance effects to sex chromosome evolution remains unclear. Springtails present a novel opportunity to ameliorate this. Male globular springtails have hemizygous X chromosomes, diploid autosomes, and eliminate their paternal genome during spermatogenesis. This leads to the autosomes matching the X chromosomes haplodiploid transmission. Hence, theoretically the X chromosomes and autosomes only differ in the fixation probability of male-beneficial alleles. We generated whole-genome resequencing and RNA-Seq data for the globular springtail Allacma fusca, to quantify the faster-X effect, leveraging this natural experiment. We find that after accounting for the deleterious distribution of fitness effects, and despite surprisingly depleted neutral X-linked diversity, the sex chromosomes show signals of both stronger purifying and positive selection, supporting the faster-X effect. Furthermore, we provide the first direct evidence for the loss of DNA methylation in Collembola. These results, obtained from a system where many of the confounding sex-autosome differences that typically obscure faster-X patterns are absent, support hemizygosity as a genuine driver of sex chromosome evolution and suggest that sex-linked genes could contribute disproportionately to adaptive potential.

evolutionary biology↗

bioRxiv2022

Accurate simultaneous sequencing of genetic and epigenetic bases in DNA

DNA comprises molecular information stored via genetic bases (G, C, T, A) and also epigenetic bases, principally 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Both genetic and epigenetic information are vital to our understanding of biology and disease states. Most DNA sequencing approaches address either genetics or epigenetics and thus capture incomplete information. Methods widely used to detect epigenetic DNA bases typically fail to capture common C-to-T mutations or distinguish 5mC from 5hmC. Here, we present a single-base-resolution sequencing methodology that will simultaneously sequence complete genetics and complete epigenetics in a single workflow. The approach is non-destructive to DNA and provides a digital readout of bases, which we exemplify by simultaneous sequencing of G, C, T, A, 5mC and 5hmC; 6-Letter sequencing. We demonstrate sequencing of human genomic DNA and also cell-free DNA taken from a blood sample of a cancer patient. The approach is accurate, requires low DNA input and has a simple workflow and analysis pipeline. We envisage it will be versatile across many applications in life sciences.

genomics↗

bioRxiv2018

FANCM-family branchpoint translocases remove co-transcriptional R-loops

Co-transcriptional R-loops arise from physiological or aberrant stalling of RNA polymerase, leading to formation of stable DNA:RNA hybrids. Unresolved R-loops can promote genome instability. Here, we show that the Fanconi anemia- and breast cancer-associated FANCM protein can directly unwind DNA-RNA hybrids from co-transcriptional R-loops in vitro. FANCM processively unwinds both short and long R-loops, irrespective of sequence, topology or coating by replication protein A. R-loops can also be unwound in the same assay by the yeast and bacterial orthologs of FANCM, Mph1 and RecG, indicating an evolutionary conserved function. Consistent with this biochemical activity of FANCM, we show that FANCM deficient cells are sensitive to drugs that stabilize R-loop formation. Our work reveals a mechanistic basis for R-loop metabolism that is critical for genome stability.

biochemistry↗