Biology subjects

Satheesh, V.

Publications and source records attributed to Satheesh, V..

4 recordsLinked to original sources

bioRxiv2026

Recurrent Duplication of the REST-NOA1 Locus Reveals a Hotspot of Regulatory Evolution Across Even-Toed Ungulates

Gene duplication is a major source of evolutionary novelty, yet recurrent duplication of the same genomic locus across independent lineages remains understudied. Using a chromosome-scale assembly and de novo annotation of the North American bison (Bison bison), we investigated the mechanisms underlying immune-system diversification in ungulates. Comparative genomics of bison, cattle, elk, and 13 mammalian species identified a large segmental duplication encompassing the regulatory genes REST and NOA1. Although similar duplications were present in 14/16 species examined, phylogenetic analyses revealed that duplicated genes cluster within species rather than across taxa, indicating repeated independent origins rather inheritance from a common ancestor. To characterize the evolutionary consequences of this duplication, we integrated transcriptomics from six tissues with weighted gene co-expression and comparative protein clustering. We identified extensive structural divergence among duplicated copies of REST and NOA1, including domain losses, truncations, and expression partitioning across tissues, consistent with functional divergence following duplication. Comparative analyses revealed substantial remodeling of immune-related genes in bison, including BOLA class I molecules, T-cell receptor genes, leukocyte immunoglobulin-like receptors, and regulators of immune signaling. These modifications included domain rearrangements, novel sequence insertions, and lineage-specific duplications associated with immune-related expression networks. Together, these findings identify the REST-NOA1 locus as a recurrent hotspot of segmental duplication in ungulates and demonstrate how repeated duplication, structural divergence, and regulatory partitioning contribute to genome evolution. These results suggest that immune system diversification in bison and related species has been shaped not only by sequence evolution but also by recurrent remodeling of regulatory pathways and antigen-recognition pathways.

bioinformatics↗

bioRxiv2026

Developing engineering strategies to enhance the genetic stability of fatty alcohol-producing strains for production scale-up

Robust strain stability is essential for industrial-scale fatty alcohol production, as metabolic burden and toxicity not only constrain productivity but also create selective pressure for low-producing or non-producing subpopulations. This genetic instability leads to genetic heterogeneity and compromises strain performance during large-scale fermentation. In this study, we investigated the production stability of fatty alcohol-producing Yarrowia lipolytica strains and developed systematic strategies to improve the genetic stability of engineered strains for scale-up production. In a mock fermentation scale-up, a fatty acyl-CoA reductase (FAR)-expressing strain lost fatty alcohol production after five consecutive passages. To address this, we fused FAR to phosphoglycerate kinase I (PGK1), a gene essential to cell growth, to promote the stability of FAR expression and prevent production loss. This strategy extended fatty alcohol production by one passage. Additionally, FAR was fused to GFP and extended production stability by four additional passages. In parallel, competitive co-culture experiments, in which producing strains were cultured alongside non-producing mutants, revealed that when non-producers emerged with a frequency of 10-5, they dominated the fermentation population within six passages; at 10%, they took only two passages. Furthermore, deep sequencing of strains that demonstrate different levels of stability and fatty alcohol productivity identified mutation patterns that contribute to strain instability. These findings provide insights into engineering Y. lipolytica with enhanced genetic stability for scale-up fatty alcohol production.

synthetic biology↗

bioRxiv2026

Hippocampal epigenetic changes associated with population cycle phase in wild voles

Vole and lemming population cycles are an enigma in ecology. Decades of field observations and experimental manipulations have revealed that cycles cannot always be explained by extrinsic factors in the environment, including food availability or predator numbers. Thus, it has been proposed that intrinsic mechanisms, such as adaptive alterations in phenotype during different phases of the cycle, drive population dynamics. However, the mechanisms underlying such phenotypic changes have not been elucidated. We test the hypothesis that epigenetic changes occur over population cycles by comparing whole epigenome DNA methylation changes in brain tissue collected from northern red-backed voles (Clethrionomys rutilus) in a wild, naturally cycling population during the peak, decline, and low years. Overall, the greatest number of differentially methylated CG sites (DMCs) and differentially methylated regions (DMRs) were detected in comparisons between voles from the peak phase and low phase of the cycle. We highlight methylation differences in the promoter region of ATP synthase subunit c (Atp5g3) and an intron of insulin-like growth factor 1 receptor (Igf1R), which may be associated with growth, development, and bioenergetics. There were additional changes in the promoters of members of the cytochrome P450 enzyme family, including Cyp1a1, associated with estrogen metabolism, as well as the promoter of macrophage migration inhibitory factor (Mif), and in an exon of serum/glucocorticoid regulated kinase (Sgk1), which may link changes in stressors to direct brain changes. Our study is the first interrogation into broad epigenetic changes associated with natural population cycle phase in a wild mammal.

ecology↗

bioRxiv2021

A H3K9me2-Binding Protein AGDP3 Limits DNA Methylation and Transcriptional Gene Silencing in Arabidopsis

DNA methylation is critical for tuning gene expression to prevent potentially deleterious gene-silencing. The Arabidopsis DNA glycosylase/lyase REPRESSOR OF SILENCING 1 (ROS1) initiates active DNA demethylation and is required for the prevention of DNA hypermethylation at thousands of genomic loci. However, the mechanism recruiting ROS1 to specific loci is not well understood. Here, we report the discovery of Arabidopsis AGENET Domain Containing Protein 3 (AGDP3) as a cellular factor required for ROS1-mediated DNA demethylation, and targets ROS1 to specific loci. We found that AGDP3 could bind to the H3K9me2 mark by its AGD12 cassette. The crystal structure of the AGDP3 AGD12 in complex with an H3K9me2 peptide reveals the molecular basis for the specific recognition, that the dimethylated H3K9 and unmodified H3K4 are specifically anchored into two different surface pockets. Interestingly, a histidine residue located in the methylysine binding aromatic cage enables AGDP3 pH-dependent H3K9me2 binding capacity. Considering the intracellular pH correlates with the histone acetylation status, our results provide the molecular mechanism for the regulation of ROS1 DNA demethylase by the gene silencing H3K9me2 mark and the potential crosstalk with active histone acetylation mark.

plant biology↗