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- Ament-Velásquez, Sandra Lorena, Ph.D. 1988-, et al.
(author)
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The Dynamics of Adaptation to Stress from Standing Genetic Variation and de novo Mutations
- 2022
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In: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 39:11
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Journal article (peer-reviewed)abstract
- Adaptation from standing genetic variation is an important process underlying evolution in natural populations, but we rarely get the opportunity to observe the dynamics of fitness and genomic changes in real time. Here, we used experimental evolution and Pool-Seq to track the phenotypic and genomic changes of genetically diverse asexual populations of the yeast Saccharomyces cerevisiae in four environments with different fitness costs. We found that populations rapidly and in parallel increased in fitness in stressful environments. In contrast, allele frequencies showed a range of trajectories, with some populations fixing all their ancestral variation in <30 generations and others maintaining diversity across hundreds of generations. We detected parallelism at the genomic level (involving genes, pathways, and aneuploidies) within and between environments, with idiosyncratic changes recurring in the environments with higher stress. In particular, we observed a tendency of becoming haploid-like in one environment, whereas the populations of another environment showed low overall parallelism driven by standing genetic variation despite high selective pressure. This work highlights the interplay between standing genetic variation and the influx of de novo mutations in populations adapting to a range of selective pressures with different underlying trait architectures, advancing our understanding of the constraints and drivers of adaptation.
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| 3. |
- Bianchi, Matteo, et al.
(author)
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Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs
- 2020
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In: BMC Genomics. - : BMC. - 1471-2164. ; 21
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Journal article (peer-reviewed)abstract
- Background: Hypothyroidism is a common complex endocrinopathy that typically has an autoimmune etiology, and it affects both humans and dogs. Genetic and environmental factors are both known to play important roles in the disease development. In this study, we sought to identify the genetic risk factors potentially involved in the susceptibility to the disease in the high-risk Giant Schnauzer dog breed.Results: By employing genome-wide association followed by fine-mapping (top variant p-value=5.7x10(-6)), integrated with whole-genome resequencing and copy number variation analysis, we detected a similar to 8.9 kbp deletion strongly associated (p-value=0.0001) with protection against development of hypothyroidism. The deletion is located between two predicted Interferon alpha (IFNA) genes and it may eliminate functional elements potentially involved in the transcriptional regulation of these genes. Remarkably, type I IFNs have been extensively associated to human autoimmune hypothyroidism and general autoimmunity. Nonetheless, the extreme genomic complexity of the associated region on CFA11 warrants further long-read sequencing and annotation efforts in order to ascribe functions to the identified deletion and to characterize the canine IFNA gene cluster in more detail.Conclusions: Our results expand the current knowledge on genetic determinants of canine hypothyroidism by revealing a significant link with the human counterpart disease, potentially translating into better diagnostic tools across species, and may contribute to improved canine breeding strategies.
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| 4. |
- Blixt, Maria, et al.
(author)
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MYCN induces cell-specific tumorigenic growth in RB1-proficient human retinal organoid and chicken retina models of retinoblastoma
- 2022
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In: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 11:1, s. 34-
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Journal article (peer-reviewed)abstract
- Retinoblastoma is a rare, intraocular paediatric cancer that originates in the neural retina and is most frequently caused by bi-allelic loss of RB1 gene function. Other oncogenic mutations, such as amplification and increased expression of the MYCN gene, have been found even with proficient RB1 function. In this study, we investigated whether MYCN over-expression can drive carcinogenesis independently of RB1 loss-of-function mutations. The aim was to elucidate the events that result in carcinogenesis and identify the cancer cell-of-origin. We used the chicken retina, a well-established model for studying retinal neurogenesis, and established human embryonic stem cell-derived retinal organoids as model systems. We over-expressed MYCN by electroporation of piggyBac genome-integrating expression vectors. We found that over-expression of MYCN induced tumorigenic growth with high frequency in RB1-proficient chicken retinas and human organoids. In both systems, the tumorigenic cells expressed markers for undifferentiated cone photoreceptor/horizontal cell progenitors. The over-expression resulted in metastatic retinoblastoma within 7–9 weeks in chicken. Cells expressing MYCN could be grown in vitro and, when orthotopically injected, formed tumours that infiltrated the sclera and optic nerve and expressed markers for cone progenitors. Investigation of the tumour cell phenotype determined that the potential for neoplastic growth was embryonic stage-dependent and featured a cell-specific resistance to apoptosis in the cone/horizontal cell lineage, but not in ganglion or amacrine cells. We conclude that MYCN over-expression is sufficient to drive tumorigenesis and that a cell-specific resistance to apoptosis in the cone/horizontal cell lineage mediates the cancer phenotype.
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| 5. |
- Bornelöv, Susanne, 1984-, et al.
(author)
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Comparative omics and feeding manipulations in chicken indicate a shift of the endocrine role of visceral fat towards reproduction
- 2018
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 19
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Journal article (peer-reviewed)abstract
- Background: The mammalian adipose tissue plays a central role in energy-balance control, whereas the avian visceral fat hardly expresses leptin, the key adipokine in mammals. Therefore, to assess the endocrine role of adipose tissue in birds, we compared the transcriptome and proteome between two metabolically different types of chickens, broilers and layers, bred towards efficient meat and egg production, respectively.Results: Broilers and layer hens, grown up to sexual maturation under free-feeding conditions, differed 4.0-fold in weight and 1.6-fold in ovarian-follicle counts, yet the relative accumulation of visceral fat was comparable. RNA-seq and mass-spectrometry (MS) analyses of visceral fat revealed differentially expressed genes between broilers and layers, 1106 at the mRNA level (FDR ≤ 0.05), and 203 at the protein level (P ≤ 0.05). In broilers, Ingenuity Pathway Analysis revealed activation of the PTEN-pathway, and in layers increased response to external signals. The expression pattern of genes encoding fat-secreted proteins in broilers and layers was characterized in the RNA-seq and MS data, as well as by qPCR on visceral fat under free feeding and 24 h-feed deprivation. This characterization was expanded using available RNA-seq data of tissues from red junglefowl, and of visceral fat from broilers of different types. These comparisons revealed expression of new adipokines and secreted proteins (LCAT, LECT2, SERPINE2, SFTP1, ZP1, ZP3, APOV1, VTG1 and VTG2) at the mRNA and/or protein levels, with dynamic gene expression patterns in the selected chicken lines (except for ZP1; FDR/P ≤ 0.05) and feed deprivation (NAMPT, SFTPA1 and ZP3) (P ≤ 0.05). In contrast, some of the most prominent adipokines in mammals, leptin, TNF, IFNG, and IL6 were expressed at a low level (FPKM/RPKM< 1) and did not show differential mRNA expression neither between broiler and layer lines nor between fed vs. feed-deprived chickens.Conclusions: Our study revealed that RNA and protein expression in visceral fat changes with selective breeding, suggesting endocrine roles of visceral fat in the selected phenotypes. In comparison to gene expression in visceral fat of mammals, our findings points to a more direct cross talk of the chicken visceral fat with the reproductive system and lower involvement in the regulation of appetite, inflammation and insulin resistance.
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| 6. |
- Brusini, Irene, et al.
(author)
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Changes in brain architecture are consistent with altered fear processing in domestic rabbits
- 2018
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:28, s. 7380-7385
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Journal article (peer-reviewed)abstract
- The most characteristic feature of domestic animals is their change in behavior associated with selection for tameness. Here we show, using high-resolution brain magnetic resonance imaging in wild and domestic rabbits, that domestication reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting that areas driving fear have lost volume while areas modulating negative affect have gained volume during domestication. In contrast to the localized gray matter alterations, white matter anisotropy was reduced in the corona radiata, corpus callosum, and the subcortical white matter. This suggests a compromised white matter structural integrity in projection and association fibers affecting both afferent and efferent neural flow, consistent with reduced neural processing. We propose that compared with their wild ancestors, domestic rabbits are less fearful and have an attenuated flight response because of these changes in brain architecture.
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| 7. |
- Carneiro, Miguel, et al.
(author)
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Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6200, s. 1074-1079
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Journal article (peer-reviewed)abstract
- The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.
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| 8. |
- Eshghi Sahraei, Shadi, et al.
(author)
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Development of a dual-host colonization system for analysis of host preference in an arbuscular mycorrhizal fungi
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Other publication (other academic/artistic)abstract
- Arbuscular mycorrhizal (AM) fungi represent a lineage of mutualistic plant symbionts, known to form biotrophic symbiosis with the vast majority vascular plant species. These ancient symbionts have been found to have low host specificity, but in nature host – fungal preferences have been observed. Over all, AM fungi increase their host fitness via providing nutrients (e.g. P, N) in exchange for photosynthetically derived carbon and energy. However, all interactions are not beneficial and negative feedback loops are important processes for maintaining plant and fungal diversity in natural ecosystems. In this study we design a dual-host growth system with F1 hybrids of sorghum and leek inoculated the hosts with the AM fungus Claroideoglomus claroideum. Host fitness and symbiotic effect following infection with AM fungus was studied using root transcriptome and 33P isotope tracing in different plant compartments. Unfortunately, very low levels of fugal transcripts were detected in sorghum roots at harvest and host specific gene expression could thus not be analysed. Both 33P isotope tracing and plant dry weight demonstrates a negative plant response to inoculation with C. claroideum for sorghum while no effect was observed for leek.
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| 10. |
- Feng, Chungang, et al.
(author)
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Moderate nucleotide diversity in the Atlantic herring is associated with a low mutation rate
- 2017
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In: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 6
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Journal article (peer-reviewed)abstract
- The Atlantic herring is one of the most abundant vertebrates on earth but its nucleotide diversity is moderate (pi = 0.3%), only three-fold higher than in human. Here, we present a pedigree-based estimation of the mutation rate in this species. Based on whole-genome sequencing of four parents and 12 offspring, the estimated mutation rate is 2.0 x 10(-9) per base per generation. We observed a high degree of parental mosaicism indicating that a large fraction of these de novo mutations occurred during early germ cell development. The estimated mutation rate the lowest among vertebrates analyzed to date - partially explains the discrepancy between the rather low nucleotide diversity in herring and its huge census population size. But a species like the herring will never reach its expected nucleotide diversity because of fluctuations in population size over the millions of years it takes to build up high nucleotide diversity.
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