Biology subjects

Salve, B. G.

Publications and source records attributed to Salve, B. G..

4 recordsLinked to original sources

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

Illuminating the mystery of thylacine extinction: a role for relaxed selection and gene loss

Gene loss shapes lineage-specific traits but is often overlooked in species survival. In this study, we investigate the role of ancestral gene loss using the extinction icon[boxh]thylacine (Thylacinus cynocephalus). While studies of neutral genetic variation indicate a population decline before extinction, the impact of thylacine-specific ancestral gene losses remains unexplored. The availability of a chromosomal-level genome of the extinct thylacine offers a unique opportunity for such comparative studies. Here, we leverage palaeogenomic data to compare gene presence/absence patterns between the Tasmanian devil and thylacine. We discovered ancestral (between 13-1 Ma) loss of SAMD9L, HSD17B13, CUZD1 and VWA7 due to multiple gene-inactivating mutations, corroborated by short-read sequencing. The loss of SAMD9 correlates with a carnivorous diet, with ancestral gene loss timing mirroring the thylacines shift to hypercarnivory. Our genome-wide analysis reveals olfactory receptor loss and relaxed selection, aligning with reduced olfactory lobes in the thylacine, indicating olfaction is not its primary hunting sense. By integrating palaeogenomic data with comparative genomics, our study reveals ancestral gene losses and their impact on species fitness while providing a foundation for selecting candidate species and genes for thylacine de-extinction. Our approach can be extended to other extinct/endangered species, highlighting genetic factors for de-extinction/conservation efforts.

genomics↗

bioRxiv2024

Evolutionary diversity of CXCL16-CXCR6: Convergent Substitutions and Recurrent Gene Loss in Sauropsids

The CXCL16-CXCR6 axis is crucial for regulating the persistence of CD8 tissue-resident memory T-cells (TRM). CXCR6 deficiency lowers TRM cell numbers in the lungs and depletes ILC3s in the lamina propria, impairing mucosal defence. This axis is linked to diseases like HIV/SIV, cancer, and COVID-19. Together, these highlight that the CXCL16-CXCR6 axis is pivotal in host immunity. Previous studies of the CXCL16-CXCR6 axis found genetic variation among species but were limited to primates and rodents. To understand the evolution and diversity of CXCL16-CXCR6 across vertebrates, we compared [~]400 1-to-1 CXCR6 orthologs spanning diverse vertebrates. The unique DRF motif of CXCR6 facilitates leukocyte adhesion by interacting with cell surface-expressed CXCL16 and plays a key role in G-protein selectivity during receptor signalling; however, our findings show that this motif is not universal. The DRF motif is restricted to mammals, turtles, and frogs, while the DRY motif, typical in other CKRs, is found in snakes and lizards. Most birds exhibit the DRL motif. These substitutions at the DRF motif affect the receptor[boxh]Gi/o protein interaction. We establish recurrent CXCR6 gene loss in 10 out of 36 bird orders, including Galliformes and Passeriformes, Crocodilia, and Elapidae, attributed to segmental deletions and/or frame-disrupting changes. Notably, single-cell RNA sequencing of the lung shows a drop in TRM cells in species with CXCR6 loss, suggesting a possible link. The concurrent loss of ITGAE, CXCL16 and CXCR6 in chickens may have altered CD8 TRM cell abundance, with implications for immunity against viral diseases and vaccines inducing CD8 TRM cells.

immunology↗

bioRxiv2023

Concurrent loss of ciliary genes WDR93 and CFAP46 in phylogenetically distant birds

The respiratory system is the primary route of infection for many contagious pathogens. Mucociliary clearance of inhaled pathogens is an important innate defense mechanism sustained by the rhythmic movement of epithelial cilia. To counter host defenses, viral pathogens target epithelial cells and cilia. For instance, the influenza virus modulates the expression of WDR93, a central ciliary apparatus C1d projection component. Lineage-specific prevalence of such host defense genes results in differential susceptibility. Our comparative analysis of [~]500 vertebrate genomes supports the widespread conservation of WDR93. However, we identified loss of the WDR93 in landfowl, geese, and other phylogenetically-independent bird species. Notably, species with WDR93 loss have concurrently lost another C1d component, CFAP46, through large segmental deletions. Understanding the consequences of such gene loss may provide insight into their role in host-pathogen interactions and benefit global pathogen surveillance efforts by prioritizing species missing host defense genes and identifying putative zoonotic reservoirs.

genomics↗