Biology subjects

H, S.

Publications and source records attributed to H, S..

5 recordsLinked to original sources

bioRxiv2026

Plant DNA Designer: A Computational Framework for Multi-Objective Codon Optimisation and Synthetic Gene Design in Crop Biotechnology

Synthetic gene design for plant transformation requires simultaneous optimisation of multiple, often competing, molecular objectives: translational efficiency, mRNA structural accessibility, codon-pair compatibility, regulatory safety, and species-specific expression context. Existing tools address these objectives in isolation, typically maximising a single metric such as the Codon Adaptation Index (CAI) and neglecting the broader determinants of in-plant expression. We present Plant DNA Designer (PDD), a web-based platform that integrates a 19-objective genetic algorithm with expression-cassette co-design, clade-aware translation-initiation logic, ribosome-velocity trajectory shaping, CRISPR guide-RNA design, and multi-gene pathway balancing across 18 crop species spanning monocot and dicot clades -- each using its own measured codon-usage table from the Kazusa Codon Usage Database. We benchmark PDD against faithful reproductions of the published algorithms of five external tools (JCat/OPTIMIZER/ATGme, IDT, TISIGNER, a CAI+GC heuristic, and a random floor) across six validated rice effector proteins. PDD is the only strategy that holds every objective within acceptable bounds at once: it reduces transgene safety liabilities from 2.3-3.5 to 0.0, and cuts deviation from a 50 % GC synthesis target from 21.8 to 4.0 percentage points, while raising codon harmony from 0.42 to 0.77 -- at a deliberate, moderate cost in raw CAI (0.79 vs 1.00). Consistent with a fair comparison rather than a strawman, a dedicated single-objective tool (IDT) still outperforms PDD on its own axis (harmony 0.93). We anchor the two central proxies against real biology: on 456 real rice genes, CAI and the wobble-weighted tAI are significantly higher in highly-expressed ribosomal-protein genes than in the genomic background (Mann-Whitney p [≤] 10-; tAI AUC 0.75) and correlate at Spearman{rho} = 0.93. Beyond this expression-class anchor, the reported design metrics are in-silico proxies, not wet-lab yield measurements. PDD is released as open-source software under an MIT licence and is freely accessible as a FastAPI web application.

bioinformatics↗

bioRxiv2025

Caenorhabditis briggsae ancestral genomic hyper-diversity contrasts with globally distributed genome-wide haplotypes

Comparative genomics provides a powerful framework to uncover the molecular and evolutionary mechanisms that shape genetic diversity within and across species, revealing how shared and lineage-specific processes influence their evolutionary trajectories through time. The nematode Caenorhabditis briggsae is distributed world-wide and is a comparative model to Caenorhabditis elegans in the biology of development, cellular mechanisms, neurobiology, genetic mappings of complex traits, and genome evolution. Following massive collection efforts by the nematode research community, we present the isolation of over 2,000 wild strains and analyses of genome sequences that catalog over six million single-nucleotide and insertion-deletion variants. This genome and strain resource provide a powerful means to interrogate the causal genetic bases of phenotypic variation for diverse traits. Additionally, we describe its global population structure and discover new and genetically distinct groups within this primarily self-fertilizing species, including groups of highly related strains that were sampled across different continents. We leverage expansive genetic variation to decipher the effects of linkage and selection on the distribution of genetic diversity across the genome and across geographic regions. Within the species, we find genomic regions with extremely high levels of genetic variation similar to hyper-divergent regions found in C. elegans and other species. These regions harbor new genes and variation enriched for environmental sensing and pathogen responses. In comparison to the outbreeding sister species Caenorhabditis nigoni, we conclude that long-term balancing selection has maintained substantial functional variation since the divergence from their outbreeding ancestor, likely in response to differences in the ecological niche. Overall, this massive strain resource enables future comparative genetics and genomics studies, including genome-wide association studies between Caenorhabditis species.

genomics↗

bioRxiv2025

Chromosomal rearrangements and segmental deletions drive gene loss in squamates

BackgroundGenomic rearrangements, including segmental deletions, duplications, translocations, and inversions of DNA segments, can contribute to gene losses, thereby reshaping genome architecture and potentially resulting in functional consequences. In squamates, karyotypic evolution mainly involves chromosome number reduction through fusions and microchromosome to macrochromosome translocations, although fissions have also contributed to diversification in several lineages. Despite these dynamics, the evolutionary processes and underlying genetic mechanisms driving chromosomal rearrangements and associated gene losses in squamates remain poorly understood. ResultsIn this study, we analysed chromosome/scaffold-level assemblies of 261 squamates, corroborated by short-read, long-read, and transcriptomic data. We found multiple lines of evidence for the putative loss of 53 genes in the squamate lineage. Synteny and phylogenetic analysis revealed that, among the 53 unretrieved orthologs, 14 are lost in squamates with no retained paralog, 15 show ortholog loss with retained paralogs, and 24 remain as unretrieved orthologs. Furthermore, we find that many of the genes lost from squamates are organised in syntenic clusters and are involved in essential immune functions--raising important questions about the role of paralogs in compensating for the function of lost genes, strengthening the "less is more" hypothesis in the squamate lineage. ConclusionsTogether, our comparative genomic analyses highlight that the loss of crucial genes in squamate lineages has occurred primarily through inter- and intrachromosomal rearrangements, including segmental deletions. These findings offer insights into the evolutionary loss of genes involved in macrophage differentiation and inform the development of novel pharmaceutical approaches for modulating immune responses.

genomics↗

bioRxiv2025

FLP-15 modulates the amplitude of body bends during locomotion in Caenorhabditis elegans

Locomotion is essential for executing most behaviours. In Caenorhabditis elegans. Efficient locomotion is exhibited as a result of the coordination of excitatory and inhibitory signals from the nervous system onto the body-wall muscles. Although neurotransmitters play a vital role in maintaining and executing coordinated movements, neuropeptides have emerged as important players in the regulation and sustenance of locomotory states. In our previous study we explored the role of the neuropeptide FLP-15 in regulating reversal frequency during foraging behaviour in C. elegans. We were also interested in exploring other possible locomotory defects in flp-15 mutant animals. In this work we show that flp-15 mutants show an increased length of reversals during foraging resulting in defects in maintaining the direction of reversals. Mutants in flp-15 exhibited a "floral" pattern of reversals as opposed to near linear patterns of reversal in wild-type control animals. We further show that the defect in maintaining the direction of reversals could be due to increased amplitude of the body-bends with flp-15 mutants showing a large increase in the mean amplitude of body-bends. Our data suggests that FLP-15 partially functions through the G-protein coupled receptor (GPCR), NPR-3, to regulates the amplitude of body-bends. Finally, we show that loss of flp-15 leads to an increase in the expression of another neuropeptide, NLP-12, whose over expression has been implicated in causing increased amplitude of body-bends allowing us to speculate that the regulation of NLP-12 by FLP-15 may allow for the observed locomotory defects in flp-15 mutant animals.

neuroscience↗

bioRxiv2025

FLP-15 functions through the GPCR NPR-3 to regulate local and global search behaviours in Caenorhabditis elegans

Foraging is essential for sustenance and well-being of all organisms. The transition from well-fed to food-deprived conditions in C. elegans triggers a localized exploration of the environment characterized by frequent reorientations. However, over time the cumulative frequency of these reorientations decreases, facilitating the transition to global search behaviour. To investigate the genetic regulation of foraging in C. elegans, we conducted a screen of neuropeptide mutants and identified several candidates involved in modulating this behaviour. Among these, neuropeptide FLP-15 emerged as a key regulator of both local and global search behaviours. Our observations revealed that FLP-15 regulates the frequency and duration of reversals during foraging. Further investigation indicated that FLP-15 is expressed in and functions through the I2 pharyngeal neuron via the G-protein coupled receptor NPR-3. Mutants lacking either flp-15 or npr-3 displayed a significant decrease in reversal frequency during local search behaviours. Interestingly, unlike wild-type animals, the reversal frequency in flp-15 and npr-3 mutants did not decrease over time. This study also describes the expression pattern of NPR-3, in a subset of head neurons, predominantly comprising of dopaminergic neurons. This expression pattern highlights a potential link between neuropeptide signalling and dopaminergic modulation of behaviour. Finally, exogenous dopamine supplementation assays revealed that FLP-15 may regulate foraging by modulating dopamine transmission, highlighting a novel neuropeptide-dopamine interaction involved in the control of foraging behaviours.

neuroscience↗