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Biology subjects

Jezuit, E.

Publications and source records attributed to Jezuit, E..

3 recordsLinked to original sources

The genome of the Pacific acorn barnacle provides insights into the evolution of extremely large populations

Population size is a key factor underlying the mode and tempo of evolution, particularly as it relates to the strength of selection and drift. While the mechanisms underlying the interactions between population size and selection have been studied in population genetics for over a century, empirical knowledge of these dynamics has been limited to species with small-to-moderate historical population sizes. This gap in knowledge highlights the need for empirical studies in systems with historically large population sizes and elevated diversity. The Pacific acorn barnacle (Balanus glandula) presents an exceptional model to study evolution in extremely large populations, exhibiting census sizes often exceeding the tens of thousands of individuals per square meter. We generated a new chromosome-level genome assembly for this species, which we leverage in one of the first large-scale genomic analyses in this system. This assembly reveals a highly polymorphic genome with over 3% heterozygosity. At a population level, B. glandula exhibits extreme levels of polymorphism, with nucleotide diversity surpassing 5% genome-wide in just a small collection of individuals. Across the genome, nucleotide diversity predictably decreases at functional elements, including both coding and non-coding sequences, likely reflecting strong purifying selection along the genome. At the same time, McDonald-Kreitman tests reveal that the majority of non-synonymous substitutions between barnacle species were driven by positive selection, consistent with the expected increase in the efficacy of selection in large populations. These remarkable levels of diversity set B. glandula as a unique model for the study of evolution at extreme demographic scales and highlights the importance of testing evolutionary theory across a wide variety of empirical systems.

evolutionary biology↗

Synaptic vesicle glycoprotein 2 enables viable aneuploidy following centrosome amplification

Amplified centrosome number causes genomic instability, most severely through division into more than two aneuploid daughter cells (multipolar mitosis). Several mechanisms that suppress multipolar division have been uncovered, yet mechanisms that favor viable multipolar division are poorly understood. To uncover factors that promote viability in cells with frequent centrosome amplification and multipolar division, we conducted an unbiased Drosophila genetic screen. In 642 mutagenized lines, we exploited the ability of intestinal papillar cells to form and function despite multipolar divisions. Our top hit is an unnamed gene, CG3168. We name this gene synaptic vesicle glycoprotein 2, reflecting homology to human Synaptic Vesicle Glycoprotein 2 (SV2) proteins. GFP-tagged SV2 localizes to the plasma membrane. In cells with amplified centrosomes, SV2 positions membrane-adjacent centrosomes, which prevents severe errors in chromosome alignment and segregation. Our results uncover membrane-based multipolar division regulation and reveal a novel vulnerability in cells with common cancer properties.

cell biology↗

Persistent DNA Repair Signaling and DNA Polymerase Theta Promote Broken Chromosome Segregation

Cycling cells must respond to double-strand breaks (DSBs) to avoid genome instability. Mis-segregation of chromosomes with DSBs during mitosis results in micronuclei, aberrant structures linked to disease. How cells respond to DSBs during mitosis is incompletely understood. We previously showed that Drosophila papillar cells lack DSB checkpoints (as observed in many cancer cells). Here, we show that papillar cells still recruit early-acting repair machinery (Mre11 and RPA3) to DSBs. This machinery persists as foci on DSBs as cells enter mitosis. Repair foci are resolved in a step-wise manner during mitosis. Repair signaling kinetics at DSBs depends on both monoubiquitination of the Fanconi Anemia (FA) protein Fancd2 and the alternative end-joining protein DNA Polymerase Theta. Disruption of either or both of these factors causes micronuclei after DNA damage, which disrupts intestinal organogenesis. This study reveals a mechanism for how cells with inactive DSB checkpoints can respond to DNA damage that persists into mitosis. SummaryClay et. al. show that cells with DNA breaks that persist into mitosis activate sustained DNA repair signaling, regulated by Fanconi Anemia proteins and the alternative end-joining repair protein DNA Polymerase Theta. This signaling enables broken chromosome segregation and prevents micronuclei.

cell biology↗