Biology subjects

Berg, F.

Publications and source records attributed to Berg, F..

4 recordsLinked to original sources

bioRxiv2025

Unheralded high MHC Class II polymorphism in the abundant Atlantic herring resolved by long-read sequencing

Major Histocompatibility Complex (MHC) genes are the most polymorphic in vertebrate genomes due to their important function of presenting a diversity of peptides from pathogens to initiate an adaptive immune response. Here, we have characterized MHC class II genes and explored their polymorphism and evolution in one of the most abundant vertebrates in the world, Atlantic herring (Clupea harengus). The vast population size and schooling behavior make Atlantic herring an attractive target for pathogens. Hence, we hypothesized that it would maintain exceptionally high MHC polymorphism. We used PacBio HiFi long-read whole genome sequencing data of 14 individuals from three different geographic regions in the Atlantic Ocean and Baltic Sea. The analysis identified nine MHC class II loci distributed across four chromosomes. We found two distinct lineages of class II genes, a highly polymorphic one denoted DA and a non-polymorphic DB lineage, arranged as alpha-beta gene pairs (DAA-DAB or DBA-DBB). The DA genes showed extremely high nucleotide diversity in exon 2, strong signatures of positive selection (dN/dS >> 1) as well as copy number variation. Structure prediction revealed that all highly polymorphic amino acid residues occurred in the predicted peptide binding cleft. Two of the most polymorphic loci showed distinct allelic groupings (supertypes), with high sequence similarity within supertypes and high sequence divergence between supertypes. Most of the haplotypes had genes from different supertypes, thus maintaining diverse class II repertoire in a single individual. There was also a highly significant nonrandom association of DAA and DAB alleles within supertypes, strongly suggesting coevolution of DAA and DAB alleles forming the peptide binding domain. This study reveals that the herring MHC class II genes are among the most, if not the most, polymorphic so far described in vertebrates. Their exceptional polymorphism surpasses that of human due to a larger gene repertoire, copy number variation, and pronounced sequence divergence among alleles. This unheralded polymorphism is most likely explained by the combined effects of the vast population size, minimizing genetic drift, and strong pathogen-driven balancing selection.

immunology↗

bioRxiv2024

Limited parallelism in genetic adaptation to brackish water bodies in European sprat and Atlantic herring

The European sprat is a small plankton-feeding clupeid present in the northeastern Atlantic Ocean, the Mediterranean Sea as well as in the brackish Baltic Sea and Black Sea. This species is the target of a major fishery and therefore an accurate characterization of its genetic population structure is crucial to delineate proper stock assessments that aid ensuring the fisherys sustainability. Here we present (i) a draft genome assembly, (ii) pooled whole genome sequencing of 19 population samples covering most of the species distribution range, and (iii) the design and test of a SNP-chip resource and use this to validate the population structure inferred from pooled sequencing. These approaches revealed, using the populations sampled here, three major groups of European sprat: Oceanic, Coastal and Brackish with limited differentiation within groups even over wide geographical stretches. Genetic structure is largely driven by six large putative inversions that differentiate Oceanic and Brackish sprats, while Coastal populations display intermediate frequencies. Interestingly, populations from the Baltic and the Black Seas share similar frequencies of haplotypes at these putative inversions despite their distant geographic location. The closely related clupeids European sprat and Atlantic herring both show genetic adaptation to the brackish Baltic Sea, providing an opportunity to explore the extent of genetic parallelism. This analysis revealed limited parallelism in the form of three sharp signals of selection that overlapped between the two species and contained single genes such as PRLRA, which encodes the receptor for prolactin, a freshwater-adapting hormone in euryhaline species, and THRB, a receptor for thyroid hormones, important both for metabolic regulation and the development of red cone photoreceptors.

genomics↗

bioRxiv2023

Efficient ultrasound-mediated drug delivery to orthotopic liver tumors: Direct comparison of doxorubicin-loaded nanobubbles and microbubbles

Liver metastasis is a major obstacle in treating aggressive cancers, and current therapeutic options often prove insufficient. To overcome these challenges, there has been growing interest in ultrasound-mediated drug delivery using lipid-shelled microbubbles (MBs) and nanobubbles (NBs) as promising strategies for enhancing drug delivery to tumors. Our previous work demonstrated the potential of Doxorubicin-loaded C3F8 NBs (hDox-NB, 280 {+/-} 123 nm) in improving cancer treatment in vitro using low-frequency ultrasound. In this study, we investigated the pharmacokinetics and biodistribution of sonicated hDox-NBs in orthotopic rat liver tumors. We compared their delivery and therapeutic efficiency with size-isolated MBs (hDox-MB, 1104 {+/-} 373 nm). Results showed a similar accumulation of hDox in tumors treated with hDox-MBs and unfocused therapeutic ultrasound (hDox-MB+TUS) and hDox-NB+TUS. However, significantly increased apoptotic cell death in the tumor and fewer off-target apoptotic cells in the normal liver were found upon the treatment with hDox-NB+TUS. The tumor-to-liver apoptotic ratio was elevated 9.4-fold following treatment with hDox-NB+TUS compared to hDox-MB+TUS, suggesting that the therapeutic efficacy and specificity are significantly increased when using hDox-NB+TUS. These findings highlight the potential of this approach as a viable treatment modality for liver tumors. By elucidating the behavior of drug-loaded bubbles in vivo, we aim to contribute to developing more effective liver cancer treatments that could ultimately improve patient outcomes and decrease off-target side effects.

bioengineering↗

bioRxiv2020

The genetic architecture underlying ecological adaptation in Atlantic herring is not consistent with the infinitesimal model

Atlantic herring is widespread in North Atlantic and adjacent waters and is one of the most abundant vertebrates on earth. This species is well suited to explore genetic adaptation due to minute genetic differentiation at selectively neutral loci. Here we report hundreds of loci underlying ecological adaptation to different geographic areas and spawning conditions. Four of these represent megabase inversions confirmed by long read sequencing. The genetic architecture underlying ecological adaptation in the herring is in conflict with the infinitesimal model for complex traits because of the large shifts in allele frequencies at hundreds of loci under selection.

evolutionary biology↗