ArticleMolecular biology and evolution2020
Evolution of the Autism-Associated Neuroligin-4 Gene Reveals Broad Erosion of Pseudoautosomal Regions in Rodents.
Article in Molecular biology and evolution, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Telomere-to-telomere genome assembly and a pangenome for the rat.Cell genomics · 2026Article
- Comparative sequence analysis of the mouse pseudoautosomal region from three inbred strains reveals it to be the most rapidly evolving 'chromosome'.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2026Article
- The association between NLGN4 gene variants and the incidence of autism spectrum disorders in Guilan, Iran.IBRO neuroscience reports · 2025Article
- The SHR/Akr Y chromosome reveals repeated turnover of the rat pseudoautosomal region.bioRxiv : the preprint server for biology · 2025Article
- The absence of Neuroligin-1 shapes wake/sleep architecture, rhythmic and arrhythmic activities of the electrocorticogram in female mice.Molecular brain · 2025Article
- Article
- Comprehensive Analysis of Rodent-SpecificBiology · 2025Article
- Unsupervised Dimensionality Reduction Techniques for the Assessment of ASD Biomarkers.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2025Article
- Review
- Construction and evaluation of a new rat reference genome assembly, GRCr8, from long reads and long-range scaffolding.Genome research · 2024Article
- Y and mitochondrial chromosomes in the heterogeneous stock rat population.G3 (Bethesda, Md.) · 2024Article
- The developmental timing of spinal touch processing alterations predicts behavioral changes in genetic mouse models of autism spectrum disorders.Nature neuroscience · 2024Article
- Increased Network Inhibition in the Dentate Gyrus of Adult Neuroligin-4 Knock-Out Mice.eNeuro · 2023Article
- Structure and evolution of neuronal wiring receptors and ligands.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Review
- Neuroligins in neurodevelopmental conditions: how mouse models ofNeuronal signaling · 2022Article
- Of Humans and Gerbils- Independent Diversification of Neuroligin-4 Into X- and Y-Specific Genes in Primates and Rodents.Frontiers in molecular neuroscience · 2022Article
- Two Functional Epithelial Sodium Channel Isoforms Are Present in Rodents despite Pronounced Evolutionary Pseudogenization and Exon Fusion.Molecular biology and evolution · 2021Article
- Odorant-binding proteins in canine anal sac glands indicate an evolutionarily conserved role in mammalian chemical communication.BMC ecology and evolution · 2021Article
- An Autism-Associated Mutation Impairs Neuroligin-4 Glycosylation and Enhances Excitatory Synaptic Transmission in Human Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y.Neuron · 2020Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Variants in genes encoding synaptic adhesion proteins of the neuroligin family, most notably neuroligin-4, are a significant cause of autism spectrum disorders in humans. Although human neuroligin-4 is encoded by two genes, NLGN4X and NLGN4Y, that are localized on the X-specific and male-specific regions of the two sex chromosomes, the chromosomal localization and full genomic sequence of the mouse Nlgn4 gene remain elusive. Here, we analyzed the neuroligin-4 genes of numerous rodent species by direct sequencing and bioinformatics, generated complete drafts of multiple rodent neuroligin-4 genes, and examined their evolution. Surprisingly, we find that the murine Nlgn4 gene is localized to the pseudoautosomal region (PAR) of the sex chromosomes, different from its human orthologs. We show that the sequence differences between various neuroligin-4 proteins are restricted to hotspots in which rodent neuroligin-4 proteins contain short repetitive sequence insertions compared with neuroligin-4 proteins from other species, whereas all other protein sequences are highly conserved. Evolutionarily, these sequence insertions initiate in the clade eumuroidea of the infraorder myomorpha and are additionally associated with dramatic changes in noncoding sequences and gene size. Importantly, these changes are not exclusively restricted to neuroligin-4 genes but reflect major evolutionary changes that substantially altered or even deleted genes from the PARs of both sex chromosomes. Our results show that despite the fact that the PAR in rodents and the neuroligin-4 genes within the rodent PAR underwent massive evolutionary changes, neuroligin-4 proteins maintained a highly conserved core structure, consistent with a substantial evolutionary pressure preserving its physiological function.
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