| 1. |
- Albert, Frank W., et al.
(författare)
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A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals
- 2012
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Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 8:9, s. e1002962-
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Tidskriftsartikel (refereegranskat)abstract
- Domestication has led to similar changes in morphology and behavior in several animal species, raising the questionwhether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing toanalyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogsand wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with thosebetween domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selectedfor tameness or aggression towards humans. There were few gene expression differences between domesticated and wilddogs, pigs, and rabbits (30–75 genes (less than 1%) of expressed genes were differentially expressed), while guinea pigs andC. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in thedifferent domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestiveevidence for the existence of a small group of genes that changed their expression in a similar fashion in differentdomesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticatedanimals and the tame and aggressive rats. However, two of the genes with the strongest expression differences betweenthe rats (DLL3 and DHDH) were located in a genomic region associated with tameness and aggression, suggesting a role ininfluencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific tothe given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise bedifferent.
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| 2. |
- Bivik, Caroline, et al.
(författare)
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Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling
- 2016
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- The Notch pathway controls proliferation during development and in adulthood, and is frequently affected in many disorders. However, the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging. Here, we address the complexity of Notch signaling with respect to proliferation, using the developing Drosophila CNS as model. We find that a Notch/Su(H)/E(spl)-HLH cascade specifically controls daughter, but not progenitor proliferation. Additionally, we find that different E(spl)-HLH genes are required in different neuroblast lineages. The Notch/Su(H)/E(spl)-HLH cascade alters daughter proliferation by regulating four key cell cycle factors: Cyclin E, String/Cdc25, E2f and Dacapo (mammalian p21(CIP1)/p27(KIP1)/p57(Kip2)). ChIP and DamID analysis of Su(H) and E(spl)-HLH indicates direct transcriptional regulation of the cell cycle genes, and of the Notch pathway itself. These results point to a multi-level signaling model and may help shed light on the dichotomous proliferative role of Notch signaling in many other systems.
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| 3. |
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| 4. |
- Eriksson, Jonas, et al.
(författare)
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Identification of the yellow skin gene reveals a hybrid origin of the domestic chicken
- 2008
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 4:2, s. e1000010-
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Tidskriftsartikel (refereegranskat)abstract
- Yellow skin is an abundant phenotype among domestic chickens and is caused by a recessive allele (W*Y) that allows deposition of yellow carotenoids in the skin. Here we show that yellow skin is caused by one or more cis-acting and tissue-specific regulatory mutation(s) that inhibit expression of BCDO2 (beta-carotene dioxygenase 2) in skin. Our data imply that carotenoids are taken up from the circulation in both genotypes but are degraded by BCDO2 in skin from animals carrying the white skin allele (W*W). Surprisingly, our results demonstrate that yellow skin does not originate from the red junglefowl (Gallus gallus), the presumed sole wild ancestor of the domestic chicken, but most likely from the closely related grey junglefowl (Gallus sonneratii). This is the first conclusive evidence for a hybrid origin of the domestic chicken, and it has important implications for our views of the domestication process.
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| 5. |
- Fernius, Josefin, et al.
(författare)
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Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis.
- 2007
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Ingår i: PLOS Genetics. - : Public Library Science. - 1553-7390 .- 1553-7404. ; 3:11
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Tidskriftsartikel (refereegranskat)abstract
- During cell division all chromosomes must be segregated accurately to each daughter cell. Errors in this process give rise to aneuploidy, which leads to birth defects and is implicated in cancer progression. The spindle checkpoint is a surveillance mechanism that ensures high fidelity of chromosome segregation by inhibiting anaphase until all kinetochores have established bipolar attachments to spindle microtubules. Bub1 kinase is a core component of the spindle checkpoint, and cells lacking Bub1 fail to arrest in response to microtubule drugs and precociously segregate their DNA. The mitotic role(s) of Bub1 kinase activity remain elusive, and it is controversial whether this C-terminal domain of Bub1p is required for spindle checkpoint arrest. Here we make a detailed analysis of budding yeast cells lacking the kinase domain (bub1DeltaK). We show that despite being able to arrest in response to microtubule depolymerisation and kinetochore-microtubule attachment defects, bub1DeltaK cells are sensitive to microtubule drugs. This is because bub1DeltaK cells display significant chromosome mis-segregation upon release from nocodazole arrest. bub1DeltaK cells mislocalise Sgo1p, and we demonstrate that both the Bub1 kinase domain and Sgo1p are required for accurate chromosome biorientation after nocodazole treatment. We propose that Bub1 kinase and Sgo1p act together to ensure efficient biorientation of sister chromatids during mitosis.
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| 6. |
- Fernius, Josefin, et al.
(författare)
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Establishment of cohesion at the pericentromere by the Ctf19 kinetochore subcomplex and the replication fork-associated factor, Csm3
- 2009
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Ingår i: PLOS Genetics. - : Public Library Science. - 1553-7390 .- 1553-7404. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- The cohesin complex holds sister chromatids together from the time of their duplication in S phase until their separation during mitosis. Although cohesin is found along the length of chromosomes, it is most abundant at the centromere and surrounding region, the pericentromere. We show here that the budding yeast Ctf19 kinetochore subcomplex and the replication fork-associated factor, Csm3, are both important mediators of pericentromeric cohesion, but they act through distinct mechanisms. We show that components of the Ctf19 complex direct the increased association of cohesin with the pericentromere. In contrast, Csm3 is dispensable for cohesin enrichment in the pericentromere but is essential in ensuring its functionality in holding sister centromeres together. Consistently, cells lacking Csm3 show additive cohesion defects in combination with mutants in the Ctf19 complex. Furthermore, delaying DNA replication rescues the cohesion defect observed in cells lacking Ctf19 complex components, but not Csm3. We propose that the Ctf19 complex ensures additional loading of cohesin at centromeres prior to passage of the replication fork, thereby ensuring its incorporation into functional linkages through a process requiring Csm3.
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| 7. |
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| 8. |
- Friberg, Urban, 1972-, et al.
(författare)
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Sexually Antagonistic “Zygotic Drive” of the Sex Chromosomes
- 2008
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Ingår i: PLOS Genetics. - : PLOS Genetics. - 1553-7390 .- 1553-7404. ; 4:12
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Tidskriftsartikel (refereegranskat)abstract
- Genomic conflict is perplexing because it causes the fitness of a species to decline rather than improve. Many diverse forms of genomic conflict have been identified, but this extant tally may be incomplete. Here, we show that the unusual characteristics of the sex chromosomes can, in principle, lead to a previously unappreciated form of sexual genomic conflict. The phenomenon occurs because there is selection in the heterogametic sex for sex-linked mutations that harm the sex of offspring that does not carry them, whenever there is competition among siblings. This harmful phenotype can be expressed as an antagonistic green-beard effect that is mediated by epigenetic parental effects, parental investment, and/or interactions among siblings. We call this form of genomic conflict sexually antagonistic “zygotic drive”, because it is functionally equivalent to meiotic drive, except that it operates during the zygotic and postzygotic stages of the life cycle rather than the meiotic and gametic stages. A combination of mathematical modeling and a survey of empirical studies is used to show that sexually antagonistic zygotic drive is feasible, likely to be widespread in nature, and that it can promote a genetic “arms race” between the homo- and heteromorphic sex chromosomes. This new category of genomic conflict has the potential to strongly influence other fundamental evolutionary processes, such as speciation and the degeneration of the Y and W sex chromosomes. It also fosters a new genetic hypothesis for the evolution of enigmatic fitness-reducing traits like the high frequency of spontaneous abortion, sterility, and homosexuality observed in humans.
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| 9. |
- Hägg, Sara, 1977-, et al.
(författare)
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Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2 : The Stockholm Atherosclerosis Gene Expression (STAGE) Study
- 2009
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Ingår i: PLoS Genetics. - : PLoS Genetics. - 1553-7390 .- 1553-7404. ; 5:12, s. e1000754-
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Tidskriftsartikel (refereegranskat)abstract
- Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n=66/tissue) and atherosclerotic and unaffected arterial wall (n=40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n=15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n=3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n=49/48) and one visceral fat (n=59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P=0.008 and P=0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n=55/54) relating to carotid stenosis (P=0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n=16/17, P<10-27and-30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, cellular and lesion expression of LDB2, and the expression of 13 TEML genes in Ldb2-deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and together with LDB2 merits further attention in CAD research.
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| 10. |
- Höglund, Andrey, 1985-, et al.
(författare)
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The regulation of methylation on the Z chromosome and the identification of multiple novel Male Hyper-Methylated regions in the chicken
- 2024
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. To investigate how variation in DNA methylation is regulated on the Z chromosome we utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals. The relatively large numbers of individuals allowed us to identify additional genomic MHM regions on the Z chromosome that were significantly differentially methylated between the sexes. These regions appear to down-regulate local gene expression in males, but not remove it entirely (unlike the lncRNAs identified in the initial MHM regions). These MHM regions were further tested and the most balanced genes appear to show decreased expression in males, whilst methylation appeared to be far more correlated with gene expression in the less balanced, as compared to the most balanced genes. In addition, trans effect hotspots were also identified that were based on the autosomes but affected the Z, and also that were based on the Z chromosome but that affected autosomal DNA methylation regulation. In addition, quantitative trait loci (QTL) that regulate variation in methylation on the Z chromosome, and those loci that regulate methylation on the autosomes that derive from the Z chromosome were mapped. Trans-effect hotspots were also identified that were based on the autosomes but affected the Z, and also one that was based on the Z chromosome but that affected both autosomal and sex chromosome DNA methylation regulation. We show that both cis and trans loci that originate from the Z chromosome never exhibit an interaction with sex, whereas trans loci originating from the autosomes but affecting the Z chromosome always display such an interaction. Our results highlight how additional MHM regions are actually present on the Z chromosome, and they appear to have smaller-scale effects on gene expression in males. Quantitative variation in methylation is also regulated both from the autosomes to the Z chromosome, and from the Z chromosome to the autosomes. DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. We utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals, to investigate the role that methylation plays in regulating gene expression on the Z chromosome. Our results highlight how additional MHM regions are actually present on the Z chromosome, and they appear to have smaller-scale effects on gene expression in males. Quantitative variation in methylation is also regulated both from the autosomes to the Z chromosome, and from the Z chromosome to the autosomes. In addition, these MHM regions were further tested and the most balanced genes appear to show decreased expression in males, whilst methylation appeared to be far more correlated with gene expression in the less balanced, as compared to the most balanced genes.
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