bioRxiv Science⌕ Search

Biology subjects

Williams, J. H.

Publications and source records attributed to Williams, J. H..

2 recordsLinked to original sources

Whole genome duplication enables rapid evolution of male-biased sex allocation in Galax urceolata

Sex allocation in hermaphrodites is thought to evolve to a balance between fitness gained through male and female function. Whole genome duplication (WGD) might disrupt such gradually evolved patterns, since it has relatively instantaneous effects on sizes, but not numbers, of cells and organs. Here we ask whether sex allocation patterns differ between young neo-autotetraploid populations and their diploid progenitors within Galax urceolata. O_LIFloral organ sizes and numbers were measured using light microscopy and genome sizes verified with flow cytometry. C_LIO_LIBoth cytotypes had the same number of flowers, anthers, and ovules per inflorescence, but floral organ sizes were proportionally longer in autotetraploids relative to diploid progenitors. Whole-plant allocation to volume of anthers increased by 176%, but of ovules only 70%. Autotetraploids produced 33% larger and 88% more pollen. C_LIO_LIWGD is known to double pollen volume, but pollen is biased to size reduction in young natural autotetraploids. In WGD-enlarged anthers, pollen size reduction allows increased pollen number to evolve without changing anther size. A literature review shows that higher pollen production in autopolyploid species is common, but not inevitable. Thus, we conclude that polyploidy can provide a pathway to increased pollen production, which may enhance male fitness during their early evolution. C_LI

evolutionary biology↗

Paralogue-selective degradation of the lysine acetyltransferase EP300

The transcriptional coactivators EP300 and CREBBP are critical regulators of gene expression that share high sequence identity but exhibit non-redundant functions in basal and pathological contexts. Here, we report the development of a bifunctional small molecule, MC-1, capable of selectively degrading EP300 over CREBBP. Using a potent aminopyridine-based inhibitor of the EP300/CREBBP catalytic domain in combination with a VHL ligand, we demonstrate that MC-1 preferentially degrades EP300 in a proteasome-dependent manner. Mechanistic studies reveal that selective degradation cannot be predicted solely by target engagement or ternary complex formation, suggesting additional factors govern paralogue-specific degradation. MC-1 inhibits cell proliferation in a subset of cancer cell lines and provides a new tool to investigate the non-catalytic functions of EP300 and CREBBP. Our findings expand the repertoire of EP300/CREBBP-targeting chemical probes and offer insights into the determinants of selective degradation of highly homologous proteins.

biochemistry↗