bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.07.01.662619

Gene gain and loss drive the diversification of gig immune genes in teleosts: structural and regulatory insights from Atlantic salmon

Abstract

Interferon-stimulated genes (ISGs) are key players in vertebrate antiviral immunity. Among teleost ISGs, the grass carp reovirus-induced gene (gig) families 1 and 2 (gig1 and gig2, respectively) are absent in mammals but conserved in fishes and amphibians, and they have been implicated in resistance to viral infections across several aquaculture species. In particular, gig1 and gig2 genes are transcriptionally induced by viral stimuli in teleosts such as zebrafish, grass carp, and salmonids, and recent studies have highlighted their potential involvement in resistance to economically important diseases like pancreas disease in Atlantic salmon. Yet, the rapid evolution of these genes hinders a comprehensive understanding of their diversification process and regulatory mechanisms. This study investigated gig gene evolution across teleosts, with a focus on Atlantic salmon (Salmo salar). Phylogenetic analysis across representative ray-finned fishes (Actinopterygii), including both teleosts and non-teleost outgroups such as the spotted gar (Holostei), indicated that gig1 is restricted to teleosts, with no identifiable homologs in non-teleost lineages. In contrast, gig2 genes are present in both teleosts and the spotted gar, suggesting an origin prior to the teleost-specific whole genome duplication (Ts3R), likely in early non-amniote vertebrates. Whole-genome duplication drove lineage-specific expansions, particularly of gig2 in salmonids. Structural and transcriptomic analyses showed that gig1 and gig2 differ in domain composition, repeat content, and regulation. Our findings suggest the complex interplay of duplication history, structural divergence, and transcriptional regulation in shaping immune gene repertoires in teleosts, with implications for understanding host-pathogen interactions and aquaculture disease responses. Article summaryThis study investigates the evolutionary history and diversification of the gig immune gene families in aquatic species, with particular focus on Atlantic salmon. Phylogenetic and structural analyses revealed that gig1 and gig2 follow distinct evolutionary trajectories, shaped by whole-genome and tandem duplications. Further analysis of Atlantic salmon gig genes showed divergent structures and regulation, highlighting a general role of gig genes in antiviral Interferon-mediated immunity and additionally suggesting functional specialization across gig paralogs. Together, these findings improve our understanding of immune gene evolution in fishes and provide insights relevant to antiviral defense and disease management in aquaculture species.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Manousi, D., Naseer, S., Martin, S. A. M., Sandve, S. R., Saitou, M.. 2025-07-05. Gene gain and loss drive the diversification of gig immune genes in teleosts: structural and regulatory insights from Atlantic salmon. https://doi.org/10.1101/2025.07.01.662619

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Genomic correlates of metastatic competence and progression in human melanoma

Genomic events and their timing that grant a primary tumour the competence to disseminate remain poorly defined. We performed sequencing of 247 stage I/II primary cutaneous melanomas (CMs) and 60 matched metastases without intervening therapy from a prospectively followed registry cohort with a median followup of 92 months, integrating copy-number, mutational, protein and spatial-transcriptomic analyses. Relapse was not distinguished by oncogenic point mutations, which were largely shared between primaries and metastases, but by somatic copy-number alterations (SCNAs) and global chromosomal instability. We defined OncoCycle, a six-gene copy-number signature (amplification of CDK4, MCL1 and CD276; biallelic loss of CDKN2A, CDKN2B and TP53BP1) that predicted relapse independently of established clinicopathological features in melanoma, and a pan-cancer analysis. In matched pairs, metastatic progression was driven by continued copy-number evolution and reduction in intra-tumoural heterogeneity, rather than by acquired point mutations, and OncoCycle alterations from primary tumours were preserved in metastasis seeding clones. Clonal reconstruction revealed both monoclonal and polyclonal metastasis seeding, and spatial transcriptomics resolved copy-number-defined metastatic subclones occupying and programming distinct immune and stromal niches. Thus, metastatic competence was primed early by focal SCNAs on a background of chromosomal instability, elaborated by continued copy-number evolution during dissemination and spatio-temporal interactions with the tumour-microenvironment.

genomics↗

PfPHAST: Plasmodium falciparum Public Health Amplicon Sequencing Tool, a Streamlined Panel for Malaria Genomic Surveillance

Genomic tools can support malaria control policy through surveillance of Plasmodium falciparum populations, tracking antimalarial drug resistance, pfhrp2/3 deletions that compromise rapid diagnostic tests, and selection at the circumsporozoite protein (PfCSP) vaccine target, as well as through molecular correction of therapeutic efficacy studies (TES). Multiplex Amplicons for Drug, Diagnostic, Diversity, and Differentiation Haplotypes using Targeted Resequencing (MAD4HatTeR), a comprehensive amplicon sequencing panel covering up to 276 targets, supports these applications but is tailored to research rather than routine programmatic use. We developed P. falciparum Public Health Amplicon Sequencing Tool (PfPHAST), a 56-target derivative of MAD4HatTeR spanning drug resistance loci, pfhrp2/3 deletion, PfCSP genotyping, non-falciparum species identification, and 20 high-heterozygosity microhaplotype loci for TES classification. We compared PfPHAST and MAD4HatTeR using laboratory strain controls, including two-strain dilution series and a five-strain mixture, across parasite densities of 100 to 10,000 parasites/L. At matched per-target depth, PfPHAST achieved a higher quality-control pass rate than MAD4HatTeR (94.4% versus 90.0%) and distributed reads more evenly across targets. The panels showed comparable recall and precision for drug resistance codons and microhaplotypes, reaching near-complete recall above 40% within-sample allele frequency (WSAF) at all densities, with reduced sensitivity for minor alleles below 10% WSAF at low parasite density in both panels. Observed and expected WSAF correlated strongly for both panels, and both resolved a five-strain polyclonal mixture, including a 5% minor strain. By concentrating sequencing capacity on targets of greatest programmatic relevance, PfPHAST offers a scalable, lower-cost alternative to comprehensive research panels without sacrificing performance on shared targets, complementing MAD4HatTeR for routine molecular malaria surveillance.

genomics↗

Structural variation in repeat elements is widespread in normal human tissues and in tumorigenesis

Somatic mosaicism contributes to genomic variation, yet postzygotic structural variants remain under-characterized. We performed long- and short-read WGS from multiple individuals (n=47 normal tissues; n=168 samples) and identified mosaic structural variants in all individuals and germ layers, impacting a median 285.2 kb/genome. Nearly half of breakpoints were independently validated, with tissue distributions reflecting both early and late developmental origins. Most mosaic variants were repeat-mediated and 8.3% overlapped functional elements, an enrichment compared to germline variants. To extend these analyses in samples where long-read sequencing is infeasible, we measured repeat alterations from short-read sequencing, recapitulating mosaic tissue-specific differences. We characterized tumor- and tissue- specific variation in repeats across 15 cancer types and found tumor-related repeat variation to be similar in scale to that of normal mosaic variation. Tracking repeat changes in cell-free DNA provided a noninvasive approach for tumor monitoring. Our analyses revealed widespread repeat-driven structural variation in health and disease.

genomics↗