Biology subjects

Mora, N.

Publications and source records attributed to Mora, N..

3 recordsLinked to original sources

bioRxiv2026

Thille, a chromosome-level type B avocado genome, and the structural and allelic variation at candidate flowering-type loci

Avocado (Persea americana Mill.) is heterodichogamous: each flower opens first as female and then as male, and cultivars fall into two complementary flowering types, A and B, determined by the transcription factor SDMYB, whose dominant allele confers type A. Avocado genomes have so far come from type A cultivars. Here we report a chromosome-level genome of Thille, a type B cultivar used in breeding. From 72.2 Gb of PacBio HiFi reads (81x coverage) and Omni-C data, the assembly places 859.8 Mb, 96% of the expected 896 Mb genome, in 12 chromosomes with an NG50 of 84.5 Mb, a consensus quality of QV 69.95, and 97.3% complete BUSCO genes; repeats occupy 64.0% of the assembly, and 35,386 protein-coding genes were predicted. We compared Thille with the type A cultivars Hass and Puebla, a predominantly Guatemalan hybrid, and with a West Indian (WI) accession, a Lowland botanical group variety of unreported flowering type. The assemblies differ by large rearrangements, including an 18.8 Mb inversion on chromosome 12 specific to Hass. Using phased reads and haplotype assemblies, we reconstructed the alleles of candidate flowering genes from a type A versus type B Fst scan. Both WI haplotypes carry the recessive SDMYB allele found in Thille; based on this study and the previous study of SDMYB, we predict the WI accession to be type B. Six genes, including SDMYB, carry an allele shared by all three type A cultivars and absent from Thille and WI. The genome and HiFi reads are available under BioProject PRJNA1142556.

genomics↗

bioRxiv2024

Glycyl-tRNA sequestration is a unifying mechanism underlying GARS1-associated peripheral neuropathy

Dominantly inherited mutations in eight cytosolic aminoacyl-tRNA synthetase genes cause hereditary motor and sensory neuropathy, characterized by degeneration of peripheral motor and sensory axons. We previously identified a pathogenic gain-of-toxic function mechanism underlying peripheral neuropathy (PN) caused by heterozygous mutations in the GARS1 gene, encoding glycyl-tRNA synthetase (GlyRS). Specifically, PN-mutant GlyRS variants sequester tRNAGly, which depletes the cellular tRNAGly pool, leading to insufficient glycyl-tRNAGly available to the ribosome and consequently ribosome stalling at glycine codons. Given that GlyRS functions as a homodimer, a subset of PN-GlyRS mutations might alternatively cause peripheral neuropathy through a dominant negative loss-of-function mechanism. To explore this possibility, we here generated three novel PN-GlyRS Drosophila models expressing human PN-GlyRS (hGlyRS) variants that do not alter the overall GlyRS protein charge (S211F and H418R) or the single reported PN-GlyRS variant that renders the GlyRS protein charge more negative (K456Q). High-level expression of hGlyRS-K456Q did not induce peripheral neuropathy and the K456Q variant does not affect aminoacylation activity, suggesting that K456Q is not a pathogenic mutation. Expression of hGlyRS-S211F or hGlyRS-H418R in Drosophila did induce peripheral neuropathy and de novo protein synthesis defects. Genetic and biochemical evidence indicates that these phenotypes were attributable to tRNAGly sequestration rather than a dominant negative mechanism. Our data identify tRNAGly sequestration as a unifying pathogenic mechanism underlying PN-GlyRS. Thus, elevating tRNAGly levels may constitute a therapeutic approach for all PN-GlyRS patients, irrespective of their disease-causing mutation.

neuroscience↗

bioRxiv2020

Generation of neuronal diversity from common progenitors via Notch signaling in the cerebellum

Brain neurons arise from relatively few progenitors capable of giving rise to an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis in both the cortex and the cerebellum is that excitatory neurons and inhibitory neurons derive from separate, spatially segregated, progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both excitatory and inhibitory lineages exist and how such a fate decision may be regulated is unknown. Using cerebellar development as a model, we discover that individual embryonic cerebellar progenitors give rise to both inhibitory and excitatory lineages. We find that gradations of Notch activity levels determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate. Daughters with intermediate levels of Notch activity become fate restricted to generate inhibitory neurons, while daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors. Graphical summary O_FIG O_LINKSMALLFIG WIDTH=144 HEIGHT=200 SRC="FIGDIR/small/997205v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@c477f8org.highwire.dtl.DTLVardef@a079bforg.highwire.dtl.DTLVardef@1992877org.highwire.dtl.DTLVardef@2fd5de_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗