| 1. |
- Höglund, Andrey, 1985-, et al.
(author)
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The methylation landscape and its role in domestication and gene regulation in the chicken
- 2020
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In: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 4, s. 1713-1724
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Journal article (peer-reviewed)abstract
- Domestication is one of the strongest examples of artificial selection and has produced some of the most extreme within-species phenotypic variation known. In the case of the chicken, it has been hypothesized that DNA methylation may play a mechanistic role in the domestication response. By inter-crossing wild-derived red junglefowl with domestic chickens, we mapped quantitative trait loci for hypothalamic methylation (methQTL), gene expression (eQTL) and behaviour. We find large, stable methylation differences, with 6,179 cis and 2,973 trans methQTL identified. Over 46% of the trans effects were genotypically controlled by five loci, mainly associated with increased methylation in the junglefowl genotype. In a third of eQTL, we find that there is a correlation between gene expression and methylation, while statistical causality analysis reveals multiple instances where methylation is driving gene expression, as well as the reverse. We also show that methylation is correlated with some aspects of behavioural variation in the inter-cross. In conclusion, our data suggest a role for methylation in the regulation of gene expression underlying the domesticated phenotype of the chicken.
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| 2. |
- Humble, Emily, et al.
(author)
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RAD Sequencing and a Hybrid Antarctic Fur Seal Genome Assembly Reveal Rapidly Decaying Linkage Disequilibrium, Global Population Structure and Evidence for Inbreeding
- 2018
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In: G3. - : GENETICS SOCIETY AMERICA. - 2160-1836. ; 8:8, s. 2709-2722
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Journal article (peer-reviewed)abstract
- Recent advances in high throughput sequencing have transformed the study of wild organisms by facilitating the generation of high quality genome assemblies and dense genetic marker datasets. These resources have the potential to significantly advance our understanding of diverse phenomena at the level of species, populations and individuals, ranging from patterns of synteny through rates of linkage disequilibrium (LD) decay and population structure to individual inbreeding. Consequently, we used PacBio sequencing to refine an existing Antarctic fur seal (Arctocephalus gazella) genome assembly and genotyped 83 individuals from six populations using restriction site associated DNA (RAD) sequencing. The resulting hybrid genome comprised 6,169 scaffolds with an N50 of 6.21 Mb and provided clear evidence for the conservation of large chromosomal segments between the fur seal and dog (Canis lupus familiaris). Focusing on the most extensively sampled population of South Georgia, we found that LD decayed rapidly, reaching the background level by around 400 kb, consistent with other vertebrates but at odds with the notion that fur seals experienced a strong historical bottleneck. We also found evidence for population structuring, with four main Antarctic island groups being resolved. Finally, appreciable variance in individual inbreeding could be detected, reflecting the strong polygyny and site fidelity of the species. Overall, our study contributes important resources for future genomic studies of fur seals and other pinnipeds while also providing a clear example of how high throughput sequencing can generate diverse biological insights at multiple levels of organization.
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| 3. |
- Höglund, Andrey, 1985-, et al.
(author)
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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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In: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 20:3
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Journal article (peer-reviewed)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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| 4. |
- Martinez Barrio, Alvaro, 1977-, et al.
(author)
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Data mining of the dog genome reveals novel Canine Endogenous Retroviruses(CfERVs)
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Other publication (pop. science, debate, etc.)abstract
- Mining the dog genome for canine endogenous retroviruses (CfERV) using the program RetroTector© identified 407 CfERVs (0.15% of the total genome size). Phylogenetic analysis showed that the majority of these CfERVs belong to the gammaretroviridae (n=313) genus. In this group, we found 33 integrated CfERVs with similarity to the human HERV-Fc1. Eighteen of them had conserved open reading frames open and seven of the 18 were recent integrations (≤ 5% LTR divergence). Some of these CfERVs may have potential for active retrotransposition and could actively contribute to the plasticity of canine genomes. Similar to other vertebrates, betaretroviruses (n=28) was the second most common group. In addition, four spuma-like and four gypsy-like CfERVs were identified, the latter group being rare in vertebrate genomes. Moreover, we identified 55 CfERVs that could not be classified unambiguously to any known retroviral genera. The integration landscape shows that all dog chromosomes have CfERV integrations with non-uniform distribution both along and across chromosomes. Some regions were essentially devoid of CfERVs whereas other regions had large numbers. Notably, in a comparison between dog and human genomes, CfERV were approximately one fifth of the amount of HERVs found. Species-specific mechanisms for purging and protection against retroviral infections are suggested to act in the dog genome. The CfERV integration pattern showed that a substantial fraction of annotated genes were found within 100 kb distance from annotated proviruses. The majority of such integrations were placed in antisense orientation relative to the transcriptional direction of the neighboring chromosomal genes. In conclusion, our results from Canis familiaris genome analysis support the notion that different mammals may interact distinctively with endogenous retroviruses.
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| 5. |
- Martinez Barrio, Alvaro, 1977-, et al.
(author)
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GeneFinder: "in silico" positional cloning of trait genes
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Other publication (pop. science, debate, etc.)abstract
- Motivation: Positional cloning of trait genes is extremely laborious and the amount of information available on gene function in different organisms is increasing so rapidly that it is hard for a research group to collect all the relevant information from a number of data sources without performing a large number of manual and time consuming searches. Results: A web service application named GeneFinder was designed and implemented. It collects selected available information related to trait loci within a given chromosomal region that control a specific phenotype. The information contains details on gene function, disease conditions, tissue expression as well as predicted gene homologies in several other species. The information gathered is further ordered by a special-purpose ranking algorithm. A web interface to the GeneFinder web service was also developed where the results are presented in a ranked list easing its interpretation. We explain the design of the architecture, show how our web interface works, and finally test a candidate region. Availability: GeneFinder is publicly available and free to use. The web interface is available at http://www.genefinder.org/.
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| 6. |
- Martínez Barrio, Álvaro, 1977-
(author)
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Novel Bioinformatics Applications for Protein Allergology, Genome-Wide Association and Retrovirology Studies
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Recently, the pace of growth in the amount of data sources within Life Sciences has increased exponentially until pose a difficult problem to efficiently manage their integration. The data avalanche we are experiencing may be significant for a turning point in science, with a change of orientation from proprietary to publicly available data and a concomitant acceptance of studies based on the latter. To investigate these issues, a Network of Excellence (EMBRACE) was launched with the aim to integrate the major databases and the most popular bioinformatics software tools. The focus of this thesis is therefore to approach the problem of seamlessly integrating varied data sources and/or distributed research tools. In paper I, we have developed a web service to facilitate allergenicity risk assessment, based on allergen descriptors, in order to characterize proteins with the potential for sensitization and cross-reactivity. In paper II, a web service was developed which uses a lightweight protocol to integrate human endogenous retrovirus (ERV) data within a public genome browser. This new data catalogue and many other publicly available sources were integrated and tested in a bioinformatics-rich client application. In paper III, GeneFinder, a distributed tool for genome-wide association studies, was developed and tested. Useful information based on a particular genomic region can be easily retrieved and assessed. Finally, in paper IV, we developed a prototype pipeline to mine the dog genome for endogenous retroviruses and displaying the transcriptional landscape of these retroviral integrations. Moreover, we further characterized a group that until this point was believed to be primate-specific. Our results also revealed that the dog has been very effective in protecting itself from such integrations. This work integrates different applications in the fields of protein allergology, biotechnology, genome association studies and endogenous retroviruses.
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| 7. |
- Sayadi, Ahmed, et al.
(author)
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The genomic footprint of sexual conflict
- 2019
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In: Nature Ecology & Evolution. - : Nature Publishing Group. - 2397-334X. ; 3:12, s. 1725-1730
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Journal article (peer-reviewed)abstract
- Genes with sex-biased expression show a number of unique properties and this has been seen as evidence for conflicting selection pressures in males and females, forming a genetic 'tug-of-war' between the sexes. However, we lack studies of taxa where an understanding of conflicting phenotypic selection in the sexes has been linked with studies of genomic signatures of sexual conflict. Here, we provide such a link. We used an insect where sexual conflict is unusually well understood, the seed beetle Callosobruchus maculatus, to test for molecular genetic signals of sexual conflict across genes with varying degrees of sex-bias in expression. We sequenced, assembled and annotated its genome and performed population resequencing of three divergent populations. Sex-biased genes showed increased levels of genetic diversity and bore a remarkably clear footprint of relaxed purifying selection. Yet, segregating genetic variation was also affected by balancing selection in weakly female-biased genes, while male-biased genes showed signs of overall purifying selection. Female-biased genes contributed disproportionally to shared polymorphism across populations, while male-biased genes, male seminal fluid protein genes and sex-linked genes did not. Genes showing genomic signatures consistent with sexual conflict generally matched life-history phenotypes known to experience sexually antagonistic selection in this species. Our results highlight metabolic and reproductive processes, confirming the key role of general life-history traits in sexual conflict.
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| 8. |
- Wright, Dominic, 1977-, et al.
(author)
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The genetic architecture of domestication in the chicken: effects of pleiotropy and linkage
- 2010
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In: Molecular Ecology. - Oxford : Blackwell Publishing Ltd. - 0962-1083 .- 1365-294X. ; 19, s. 5140-5156
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Journal article (peer-reviewed)abstract
- The extent of pleiotropy and epistasis in quantitative traits remains equivocal. In the caseof pleiotropy, multiple quantitative trait loci are often taken to be pleiotropic if theirconfidence intervals overlap, without formal statistical tests being used to ascertain ifthese overlapping loci are statistically significantly pleiotropic. Additionally, the degreeto which the genetic correlations between phenotypic traits are reflected in thesepleiotropic quantitative trait loci is often variable, especially in the case of antagonisticpleiotropy. Similarly, the extent of epistasis in various morphological, behavioural andlife-history traits is also debated, with a general problem being the sample sizes requiredto detect such effects. Domestication involves a large number of trade-offs, which arereflected in numerous behavioural, morphological and life-history traits which haveevolved as a consequence of adaptation to selective pressures exerted by humans andcaptivity. The comparison between wild and domestic animals allows the geneticanalysis of the traits that differ between these population types, as well as being ageneral model of evolution. Using a large F2 intercross between wild and domesticatedchickens, in combination with a dense SNP and microsatellite marker map, bothpleiotropy and epistasis were analysed. The majority of traits were found to segregate in11 tight ‘blocks’ and reflected the trade-offs associated with domestication. These blockswere shown to have a pleiotropic ‘core’ surrounded by more loosely linked loci. Incontrast, epistatic interactions were almost entirely absent, with only six pairs identifiedover all traits analysed. These results give insights both into the extent of such blocks inevolution and the development of domestication itself.
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