Biology subjects

Andersson, L.

Publications and source records attributed to Andersson, L..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

The origin and maintenance of supergenes contributing to ecological adaptation in Atlantic herring

Chromosomal inversions are associated with local adaptation in many species. However, questions regarding how they are formed, maintained and impact various other evolutionary processes remain elusive. Here, using a large genomic dataset of long-read and short-read sequencing, we ask these questions in one of the most abundant vertebrates on Earth, the Atlantic herring. This species has four megabase-sized inversions associated with ecological adaptation that correlate with water temperature. The S and N inversion alleles at these four loci dominate in the southern and northern parts, respectively, of the species distribution in the North Atlantic Ocean. By determining breakpoint coordinates of the four inversions and the structural variations surrounding them, we hypothesize that these inversions are formed by ectopic recombination between duplicated sequences immediately outside of the inversions. We show that these are old inversions (>1 MY), albeit formed after the split between Atlantic herring and its sister species, the Pacific herring. They are yet to reach mutation-flux equilibrium, but the large Ne of herring combined with the common occurrence of opposite homozygotes across the species distribution has allowed effective purifying selection to prevent accumulation of genetic load and repeats within the inversions.

evolutionary biology↗

bioRxiv2023

Conservation of affinity rather than sequence underlies a dynamic evolution of the motif-mediated p53/MDM2 interaction in teleosts

The transcription factor and cell cycle regulator p53 is marked for degradation by the ubiquitin ligase MDM2. The interaction between these two proteins is mediated by a conserved binding motif in the disordered p53 transactivation domain (p53TAD) and the folded SWIB domain in MDM2. The conserved motif in p53TAD from zebrafish displays a 20-fold weaker interaction with MDM2, compared to the interaction in human and chicken. To investigate this apparent difference, we tracked the molecular evolution of the p53TAD/MDM2 interaction among ray- finned fishes (Actinopterygii), the largest vertebrate clade. Intriguingly, phylogenetic analyses, ancestral sequence reconstructions, and binding experiments showed that different loss-of- affinity changes in the canonical binding motif within p53TAD have occurred repeatedly and convergently in different fish lineages, resulting in relatively low extant affinities (KD = 0.5-5 M). However, for eleven different fish p53TAD/MDM2 interactions, non-conserved regions flanking the canonical motif increased the affinity 4 to 73-fold to be on par with the human interaction. Our findings suggest that compensating changes at conserved and non-conserved positions within the motif, as well as in flanking regions of low conservation, underlie a stabilizing selection of "functional affinity" in the p53TAD/MDM2 interaction. Such interplay complicates bioinformatic prediction of binding and call for experimental validation. Motif- mediated protein-protein interactions involving short binding motifs and folded interaction domains are very common across multicellular life. It is likely that evolution of affinity in motif- mediated interactions often involves an interplay between specific interactions made by conserved motif residues and non-specific interactions by non-conserved disordered regions.

molecular biology↗

bioRxiv2023

Introgression underlies phylogenetic uncertainty but not parallel plumage evolution in a recent songbird radiation

Instances of parallel phenotypic evolution offer great opportunities to understand the evolutionary processes underlying phenotypic changes. However, confirming parallel phenotypic evolution and studying its causes requires a robust phylogenetic framework. One such example is the "black-and-white wagtails", a group of five species in the songbird genus Motacilla: one species, the White Wagtail (M. alba), shows wide intra-specific plumage variation, while the four others form two pairs of very similar-looking species (African Pied Wagtail M. aguimp + Mekong Wagtail M. samveasnae and Japanese Wagtail M. grandis + White-browed Wagtail M. maderaspatensis, respectively). However, the two species in each of these pairs were not recovered as sisters in previous phylogenetic inferences. Their relationships varied depending on the markers used, suggesting that gene tree heterogeneity might have hampered accurate phylogenetic inference. Here, we use whole genome resequencing data to explore the phylogenetic relationships within this group, with a special emphasis on characterizing the extent of gene tree heterogeneity and its underlying causes. We first used multispecies coalescent methods to generate a "complete evidence" phylogenetic hypothesis based on genome-wide variants, while accounting for incomplete lineage sorting and introgression. We then investigated the variation in phylogenetic signal across the genome, to quantify the extent of discordance across genomic regions, and test its underlying causes. We found that wagtail genomes are mosaics of regions supporting variable genealogies, because of ILS and inter-specific introgression. The most common topology across the genome, supporting M. alba and M. aguimp as sister species, appears to be influenced by ancient introgression. Additionally, we inferred another ancient introgression event, between M. alba and M. grandis. By combining results from multiple analyses, we propose a phylogenetic network for the black-and-white wagtails that confirms that similar phenotypes evolved in non-sister lineages, supporting parallel plumage evolution. Furthermore, the inferred reticulations do not connect species with similar plumage coloration, suggesting that introgression does not underlie parallel plumage evolution in this group. Our results demonstrate the importance of investigation of genome-wide patterns of gene tree heterogeneity to help understanding the mechanisms underlying phenotypic evolution.

evolutionary biology↗

bioRxiv2023

ZC3H11A interacts with PABPN1 and alters polyadenylation of viral transcripts

Nuclear mRNA metabolism is regulated by multiple proteins, which either directly bind to RNA or form multi-protein complexes. The RNA-binding protein ZC3H11A is involved in nuclear mRNA export, and NF-{kappa}B signaling and is essential during mouse embryo development. Furthermore, previous studies have shown that ZC3H11A is important for nuclear-replicating viruses. However, detailed biochemical characterization of the ZC3H11A protein has been lacking. In this study, we established the ZC3H11A protein interactome in human and mouse cells. We demonstrate that the nuclear poly(A)-binding protein PABPN1 interacts specifically with the ZC3H11A protein and controls ZC3H11A localization into nuclear speckles. We report that ZC3H11A specifically interacts with the human adenovirus type 5 (HAdV-5) capsid mRNA in a PABPN1-dependent manner. Notably, ZC3H11A uses the same zinc finger motifs to interact with PABPN1 and mRNA, with a single zinc finger motif responsible for these functions. Further, we demonstrate that the lack of ZC3H11A alters the polyadenylation of HAdV-5 capsid mRNA. Taken together, our results suggest that the ZC3H11A protein acts as a novel regulator of polyadenylation of nuclear mRNA.

molecular biology↗

bioRxiv2022

Large effect loci have a prominent role in Darwin's finch evolution

A fundamental goal in evolutionary biology is to understand the genetic architecture of adaptive traits and its evolutionary relevance. Using whole-genome data of 3,958 Darwins finches on the Galapagos Island of Daphne Major we identify six loci of large effect that explain 46% of the variation in beak size of Geospiza fortis, a key ecological trait. Allele frequency changes across 30 years at these loci affected beak morphology in two ways. An abrupt change in beak size occurred in Geospiza fortis as a result of natural selection associated with a drought, and a more gradual change occurred in G. scandens as a result of introgressive hybridization. This study demonstrates how large effect loci are a major contributor to the genetic architecture of rapid diversification during adaptive radiations. One Sentence SummaryAllele frequency change at six loci of large effect causes evolutionary change in key ecological traits.

evolutionary biology↗

bioRxiv2022

Ablation of ZC3H11A causes early embryonic lethality and dysregulation of metabolic processes

ZC3H11A is a stress-induced mRNA binding protein required for efficient growth of nuclear-replicating viruses, while being dispensable for the viability of cultured human cells. The cellular functions of ZC3H11A during embryo development are unknown. Here we report the generation and phenotypic characterization of Zc3h11a knock-out mice. Heterozygous null Zc3h11a mice were born at the expected frequency without distinguishable phenotypic differences compared with wild-type. In contrast, homozygous null Zc3h11a mice were missing, indicating that Zc3h11a is crucial for embryonic viability and survival. Zc3h11a-/- embryos were detected at the expected Mendelian ratios up to late preimplantation stage (E4.5). However, phenotypic characterization at E6.5 revealed degeneration of Zc3h11a-/- embryos, indicating developmental defects around the time of implantation. Transcriptomic analyses documented a dysregulation of glycolysis and fatty acid metabolic pathways in Zc3h11a-/- embryos at E4.5. Proteomic analysis indicated a tight interaction between ZC3H11A and mRNA-export proteins in embryonic stem cells. Furthermore, CLIP-seq analysis demonstrated that ZC3H11A binds a subset of mRNA transcripts that are critical for metabolic regulation of embryonic cells. Altogether, the results show that ZC3H11A is participating in export and post-transcriptional regulation of selected mRNA transcripts required to maintain metabolic processes in embryonic cells. While ZC3H11A is essential for the viability of the early mouse embryo, inactivation of Zc3h11a expression in adult tissues using a conditional knock-out did not lead to obvious phenotypic defects.

cell biology↗

bioRxiv2022

Heterotopic ossification in intact rat Achilles tendons is characterized by unique mineralized collagen fiber structures

Heterotopic ossification (HO) entails pathological mineral formation inside soft tissues. In human Achilles tendons, HO is often associated with tendinopathies, tendon weakness and pain. One hypothesis is that HO occurs in response to inflammation and by either intramembranous ossification, endochondral ossification, or a combination of both. However, refined details regarding HO deposition and microstructure are still unknown. In this study, we characterize HO in intact rat Achilles tendons through high-resolution phase contrast enhanced synchrotron X-ray tomographic imaging. Furthermore, we test the potential of using a procedure to induce local tissue injury by needling to study the relation between microdamage and formation of HO. The results show that HO occurs in all intact rat tendons occupying up to 1% of the total volume at 16 weeks of age. The HOs are characterized by an elongated ellipsoidal shape and by a distinctive fiber-like internal structure which suggests that some collagen fibers have become mineralized. The data indicates that the deposition along the fibers initiates in the pericellular area, and propagates into the intercellular area. The results also show that multiple HO deposits may merge into bigger structures with time by accession along unmineralized fibers. Furthermore, the presence of unmineralized regions within the deposits may indicate that HOs are not only growing, but mineral resorption can also occur. Additionally, phase contrast enhanced synchrotron X-ray tomography allowed to distinguish microdamage at the fiber level due to needling and it could in the future enable to elucidate the relation between local inflammation, microdamage, and HO deposition.

physiology↗

bioRxiv2022

Low mutation load in a supergene underpinning alternative male mating strategies in ruff

Ruffs are shorebirds with an elaborate lekking behavior involving three male morphs with different mating strategies: Independents, Satellites, and Faeders1,2. The latter two are heterozygous for different versions of a supergene maintained by an inversion that were estimated to have occurred about 4 million years ago3. Faeders carry an intact inversion while the Satellite allele is recombinant, both of which are expected to accumulate high mutational load because they are recessive lethals. Here we have constructed a highly contiguous genome assembly of the inversion region for both the Independent and Satellite haplotypes. The recombination event(s) between an inverted and non-inverted chromosome creating the Satellite allele must have occurred recently (within the last 100,000 years) based on the minute sequence divergence between the Satellite and Independent alleles in the recombinant regions. Contrary to expectations4,5, we find no expansion of repeats and only a very modest mutation load on the Satellite allele in the nonrecombinant region despite high sequence divergence (1.46%). The essential centromere protein CENPN gene is disrupted by the inversion, and surprisingly is as well conserved on the inversion haplotypes as on the noninversion haplotype. The results suggest that the inversion may be much younger than previously thought. The lack of mutation load despite recessive lethality can be explained by the introgression of the inversion from a now extinct lineage.

evolutionary biology↗

bioRxiv2022

The genomic basis and environmental correlates of local adaptation in the Atlantic horse mackerel (Trachurus trachurus)

Understanding how populations adapt to local environments is increasingly important to prevent biodiversity loss due to climate change. Here we examined whole-genome variation of twelve Atlantic horse mackerel samples from the North Sea to North Africa, and the western Mediterranean Sea. This marine migratory benthopelagic fish is one of the most widely distributed and commercially important species in the eastern Atlantic. We found low population structure at neutral loci, but high differentiation at adaptive loci distinguishing the western Mediterranean and the North Sea populations from other Atlantic locations. Candidate genes distinctive of the Mediterranean include a green-sensitive-opsin harbouring two missense mutations that might fine-tune the spectral sensitivity to blue-green light conditions. Candidate genes characteristic of the North Sea could play a critical role in cold tolerance (energy metabolism and cell membrane structure) and increased sensitivity to odours, presumably to compensate reduced visibility in turbid waters. We also discovered a putative chromosomal inversion (9.9 Mb) that follows a climate-related latitudinal cline with a break near mid Portugal. Genome-environment association analysis indicated that seawater-dissolved oxygen concentration and temperature are likely the main environmental drivers of local adaptation. Our genomic data broadly supports the current stock divisions, but recommends revision of the western and southern stock boundaries. We developed a reduced SNP panel that genetically discriminate the North Sea and North Africa from neighbouring populations. Our study highlights the importance of life history and chromosomal inversions in adaptation with gene flow, and the complexity of evolutionary and ecological processes involved in local adaptation.

genomics↗

bioRxiv2022

A baseline for the genetic stock identification of Atlantic herring, Clupea harengus, in ICES Divisions 6.a, 7.b-c

Atlantic herring in ICES Divisions 6.a, 7.b-c comprises at least three populations, distinguished by temporal and spatial differences in spawning, which have until recently been managed as two stocks defined by geographic delineators. Outside of spawning the populations form mixed aggregations, which are the subject of acoustic surveys. The inability to distinguish the populations has prevented the development of separate survey indices and separate stock assessments. A panel of 45 SNPs, derived from whole genome sequencing, were used to genotype 3,480 baseline spawning samples (2014-2021). A temporally stable baseline comprising 2,316 herring from populations known to inhabit Division 6.a was used to develop a genetic assignment method, with a self-assignment accuracy >90%. The long-term temporal stability of the assignment model was validated by assigning archive (2003-2004) baseline samples (270 individuals) with a high level of accuracy. Assignment of non-baseline samples (1,514 individuals) from Division 6.a, 7.b-c indicated previously unrecognised levels of mixing of populations outside of the spawning season. The genetic markers and assignment models presented constitute a toolbox that can be used for the assignment of herring caught in mixed survey and commercial catches in Division 6.a into their population of origin with a high level of accuracy.

zoology↗

bioRxiv2022

Spatiotemporal variations in retrovirus-host interactions among Darwin's finches

Endogenous retroviruses (ERVs) are inherited remnants of past retroviruses that colonized host germline over millions of years, providing a sampling of retroviral diversity across time. The utility of ERVs as markers of host genome evolution is augmented by their ability to reveal historic retrovirus-host interactions, given that ERVs are examples of active retroviruses at the time of germline invasion. Here, we utilize the strength of Darwins finches, a system synonymous with evolutionary studies, for investigating ERV history, revealing recent retrovirus-host interactions in natural populations. By mapping ERV variation across all species of Darwins finches and comparing with outgroup species, we highlight geographical and historical patterns of retrovirus-host occurrence, utilizing the system as a natural model for evaluating the extent and timing of retroviral activity in hosts undergoing adaptive radiation and colonization of new environments. We found shared ERVs among all samples indicating retrovirus-host associations pre-dating host speciation, as well as considerable ERV variation across populations of the entire Darwins finches radiation. Unexpected ERV variation in finch species on different islands suggest historical changes in gene flow and selection. Non-random distribution of ERVs along and between chromosomes, as well as across finch species, suggests association between ERV accumulation and the rapid speciation of Darwins finches.

evolutionary biology↗

bioRxiv2021

Darwin's finches - an adaptive radiation constructed from ancestral genetic modules

Recent adaptive radiations are models for investigating mechanisms contributing to the evolution of biodiversity. An unresolved question is the relative importance of new mutations, ancestral variants, and introgressive hybridization for phenotypic evolution and speciation. Here we address this issue using Darwins finches, which vary in size from an 8g warbler finch with a pointed beak to a 40g large ground finch with a massive blunt beak. We present a highly contiguous genome assembly for one of the species and investigate the genomic architecture underlying phenotypic diversity in the entire radiation. Admixture mapping for beak and body size in the small, medium and large ground finches revealed 28 loci showing strong genetic differentiation. These loci represent ancestral haplotype blocks with origins as old as the Darwins finch phylogeny (1-2 million years). Genes expressed in the developing beak are overrepresented in these genomic regions. Frequencies of allelic variants at the 28 loci covary with phenotypic similarities in body and beak size across the Darwins finch phylogeny. These ancestral haplotypes constitute genetic modules for selection, and act as key determinants of the exceptional phenotypic diversity of Darwins finches. Such ancestral haplotype blocks can be critical for how species adapt to environmental variability and change.

evolutionary biology↗

bioRxiv2021

Transspecies beak color polymorphism in the Darwin's finch radiation

Carotenoid-based polymorphisms are widespread in populations of birds, fish, and reptiles1, but little is known of how they affect fitness and are maintained as species multiply2. We report a combined field and molecular-genetic investigation of a nestling beak color polymorphism in Darwins finches. Beaks are pink or yellow, and yellow is recessive3. Here we show that the polymorphism arose in the Galapagos approximately half a million years ago through a regulatory mutation in the BCO2 gene, and is shared by 14 descendant species. The frequency of the yellow genotype is associated with cactus flower abundance in cactus finches, and is altered by introgressive hybridization. The polymorphism is most likely a balanced polymorphism, maintained by ecological selection pressures associated with diet, and augmented by occasional interspecific introgression. Polymorphisms that are hidden as adults, as here, may contribute to evolutionary diversification in underappreciated ways in other systems.

evolutionary biology↗

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↗

bioRxiv2020

A point mutation in Ttc26 causes lumbar spinal cord fusion and synchronous hind-limb locomotion in hop mice

Identifying the spinal circuits controlling locomotion is critical for unravelling the mechanisms controlling the production of gaits. Development of the circuits governing left-right coordination relies on axon guidance molecules such as ephrins and netrins. To date, no other class of proteins have been shown to play a role during this process. Here we have analyzed hop mice, which walk with a characteristic hopping gait using their hind legs in synchrony. Fictive locomotion experiments suggest that a local defect in the ventral spinal cord contributes to the aberrant locomotor phenotype. Hop mutant spinal cords had severe morphological defects, including the absence of the ventral midline and a poorly defined border between white and grey matter. The hop mice represent the first model where the left and right central pattern generators (CPGs) are fused to form one central CPG, with a synchronous gait as a functional consequence. These defects were exclusively found in the lumbar domain and were associated with abnormal developmental processes, including a misplaced notochord and reduced induction of ventral progenitor domains. While the underlying mutation in hop mice has been suggested to lie within Ttc26, other genes in close vicinity have been associated with gait defects. By replicating the point mutation within Ttc26, employing CRISPR technology, we observed mice with an identical phenotype, thereby verifying the hop mutation. Thus, we show that the assembly of the lumbar CPG network is dependent on a fully functional TTC26 protein.

neuroscience↗

bioRxiv2019

A chromosome-level assembly of the Atlantic herring - detection of a supergene and other signals of selection

The Atlantic herring is a model species for exploring the genetic basis for ecological adaptation, due to its huge population size and extremely low genetic differentiation at selectively neutral loci. However, such studies have so far been hampered because of a highly fragmented genome assembly. Here, we deliver a chromosome-level genome assembly based on a hybrid approach combining a de novo PacBio assembly with Hi-C-supported scaffolding. The assembly comprises 26 autosomes with sizes ranging from 12.4 to 33.1 Mb and a total size, in chromosomes, of 726 Mb. The development of a high-resolution linkage map confirmed the global chromosome organization and the linear order of genomic segments along the chromosomes. A comparison between the herring genome assembly with other high-quality assemblies from bony fishes revealed few interchromosomal but frequent intrachromosomal rearrangements. The improved assembly makes the analysis of previously intractable large-scale structural variation more feasible; allowing, for example, the detection of a 7.8 Mb inversion on chromosome 12 underlying ecological adaptation. This supergene shows strong genetic differentiation between populations from the northern and southern parts of the species distribution. The chromosome-based assembly also markedly improves the interpretation of previously detected signals of selection, allowing us to reveal hundreds of independent loci associated with ecological adaptation in the Atlantic herring.

genomics↗

bioRxiv2019

Liver-Chip: Reproducing Human and Cross-Species Toxicities

Nonclinical rodent and non-rodent toxicity models used to support clinical trials of candidate drugs may produce discordant results or fail to predict complications in humans contributing to drug failures in the clinic. Here we applied microengineered Organ-on-Chip (Organ-Chip) technology to design rat, dog, and human Liver-Chips containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, with or without Kupffer cells and hepatic stellate cells, cultured under physiological fluid flow. The Liver-Chips detected diverse phenotypes of liver toxicity including hepatocellular injury, steatosis, cholestasis, and fibrosis as well as species-specific toxicities when treated with tool compounds. Multi-species Liver-Chips may provide a useful platform for prediction of liver toxicity and inform human relevance of liver toxicities detected in animal studies to better determine safety and human risk.\n\nOne Sentence SummaryMicroengineered Organ-Chip technology has been used to design rat, dog and human Liver-Chips that recapitulate species-specific liver toxicities.

pharmacology and toxicology↗

bioRxiv2019

Adaptation to seasonal reproduction and thermal minima-related factors drives fine-scale divergence despite gene flow in Atlantic herring populations

Natural selection can maintain local adaptation despite the presence of gene flow. However, the genomic basis and environmental factors involved in adaptation at fine-spatial scales are not well understood. Here, we address these questions using Atlantic herring (Clupea harengus), an abundant, migratory, and widely distributed marine species with substantial genomic resources including a chromosome-level genome assembly and genomic data from the eastern Atlantic and Baltic populations. We analysed whole-genome sequence and oceanographic data to examine the genetic variation of 15 spawning aggregations across the northwest Atlantic Ocean ([~]1,600 km of coastline) and the association of this variation with environmental variables. We found that population structure lies in a small fraction of the genome involving adaptive genetic variants of functional importance. We discovered 10 highly differentiated genomic regions distributed across four chromosomes. Two of these loci appear to be private to the northwest, four loci share a large number of adaptive variants between northwest and northeast Atlantic, and four shared loci exhibit an outstanding diversity in haplotype composition, including a novel putative inversion on chromosome 8. Another inversion on chromosome 12 underlies a latitudinal genetic pattern discriminating populations north and south of a biogeographic transition zone on the Scotian Shelf. Our genome-environment association analysis indicates that sea water temperature during winter is the environmental factor that best correlates with the latitudinal pattern of this inversion. We conclude that the timing and geographic location of spawning and early development are under diverse selective pressures related to environmental gradients. Natural selection appears to act on early-life performance traits with differential fitness across environments. Our study highlights the role of genomic architecture, ancestral haplotypes, and selection in maintaining adaptive divergence in species with large population sizes and presumably high gene flow.

genomics↗