| 1. |
- Basile, Walter, 1980-
(författare)
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Orphan Genes Bioinformatics : Identification and properties of de novo created genes
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Even today, many genes are without any known homolog. These "orphans" are found in all species, from Viruses to Prokaryotes and Eukaryotes. For a portion of these genes, we might simply not have enough data to find homologs yet. Some of them are imported from taxonomically distant organisms via lateral transfer; others have homologs, but mutated beyond the point of recognition.However, a sizeable fraction of orphan genes is unambiguously created via "de novo" mechanisms. The study of such novel genes can contribute to our understanding of the emergence of functional novelty and the adaptation of species to new ecological niches.In this work, we first survey the field of orphan studies, and illustrate some of the common issues. Next, we analyze some of the intrinsic properties of orphans proteins, including secondary structure elements and Intrinsic Structural Disorder; specifically, we observe that in young proteins the relationship between these properties and the G+C content of their coding sequence is stronger than in older proteins.We then tackle some of the methodological problems often found in orphan studies. We find that using evolutionarily close species, and sensitive, state-of-the art homology recognition methods is instrumental to the identification of a set of orphans enriched in de novo created ones.Finally, we compare how intrinsic disorder is distributed in bacteria versus eukaryota. Eukaryotic proteins are longer and more disordered; the difference is to be attributed primarily to eukaryotic-specific domains and linker regions. In these sections of the proteins, a higher frequency of the disorder-promoting amino acid Serine can be observed in Eukaryotes.
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| 2. |
- Brandström, Mikael, 1978-
(författare)
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Bioinformatic Analysis of Mutation and Selection in the Vertebrate Non-coding Genome
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The majority of the vertebrate genome sequence is not coding for proteins. In recent years, the evolution of this noncoding fraction of the genome has gained interest. These studies have been greatly facilitated by the availability of full genome sequences. The aim of this thesis is to study evolution of the noncoding vertebrate genome through bioinformatic analysis of large-scale genomic datasets.In a first analysis we addressed the use of conservation of sequence between highly diverged genomes to infer function. We provided evidence for a turnover of the patterns of negative selection. Hence, measures of constraint based on comparisons of diverged genomes might underestimate the functional proportion of the genome.In the following analyses we focused on length variation as found in small-scale insertion and deletion (indel) polymorphisms and microsatellites. For indels in chicken, replication slippage is a likely mutation mechanism, as a large proportion of the indels are parts of tandem-duplicates. Using a set of microsatellite polymorphisms in chicken, where we avoid ascertainment bias, we showed that polymorphism is positively correlated with microsatellite length and AT-content. Furthermore, interruptions in the microsatellite sequence decrease the levels of polymorphism.We also analysed the association between microsatellite polymorphism and recombination in the human genome. Here we found increased levels of microsatellite polymorphism in human recombination hotspots and also similar increases in the frequencies of single nucleotide polymorphisms (SNPs) and indels. This points towards natural selection shaping the levels of variation. Alternatively, recombination is mutagenic for all three kinds of polymorphisms. Finally, I present the program ILAPlot. It is a tool for visualisation, exploration and data extraction based on BLAST.Our combined results highlight the intricate connections between evolutionary phenomena. It also emphasises the importance of length variability in genome evolution, as well as the gradual difference between indels and microsatellites.
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| 3. |
- Linnenbrink, Miriam, et al.
(författare)
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Experimental Evaluation of a Direct Fitness Effect of the De Novo Evolved Mouse Gene Pldi
- 2024
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Ingår i: GENOME BIOLOGY AND EVOLUTION. - 1759-6653. ; 16:5
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Tidskriftsartikel (refereegranskat)abstract
- De novo evolved genes emerge from random parts of noncoding sequences and have, therefore, no homologs from which a function could be inferred. While expression analysis and knockout experiments can provide insights into the function, they do not directly test whether the gene is beneficial for its carrier. Here, we have used a seminatural environment experiment to test the fitness of the previously identified de novo evolved mouse gene Pldi, which has been implicated to have a role in sperm differentiation. We used a knockout mouse strain for this gene and competed it against its parental wildtype strain for several generations of free reproduction. We found that the knockout (ko) allele frequency decreased consistently across three replicates of the experiment. Using an approximate Bayesian computation framework that simulated the data under a demographic scenario mimicking the experiment's demography, we could estimate a selection coefficient ranging between 0.21 and 0.61 for the wildtype allele compared to the ko allele in males, under various models. This implies a relatively strong selective advantage, which would fix the new gene in less than hundred generations after its emergence.
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| 4. |
- Prpic, Nikola-Michael, et al.
(författare)
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Evolution of dorsal–ventral axis formation in arthropod appendages : H15 and optomotor-blind/bifid-type T-box genes in the millipede Glomeris marginata (Myriapoda: Diplopoda)
- 2005
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Ingår i: Evolution & Development. - 1520-541X .- 1525-142X. ; 7:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- In Drosophila, the T-box genes optomotor-blind (omb) and H15 have been implicated in specifying the development of the dorso-ventral (DV) axis of the appendages. Results from the spider Cupiennius salei have suggested that this DV patterning system may be at least partially conserved. Here we extend the study of the DV patterning genes omb and H15 to a representative of the Myriapoda in order to add to the existing comparative data set and to gain further insight into the evolution of the DV patterning system in arthropod appendages. The omb gene of the millipede Glomeris marginata is expressed on the dorsal side of all appendages including trunk legs, maxillae, mandibles, and antennae. This is similar to what is known from Drosophila and Cupiennius and suggests that the role of omb in instructing dorsal fates is conserved in arthropods. Interestingly, the lobe-shaped portions of the mouthparts do not express omb, indicating that these are ventral components and thus may be homologous to the endites present in the corresponding appendages in insects. Concerning the H15 gene we were able to identify two paralogous genes in Glomeris. Both genes are expressed in the sensory organs of the maxilla and antenna, but only Gm-H15-1 is expressed along the ventral side of the trunk legs. The expression is more extensive than in Cupiennius, but less so than in Drosophila. In addition, no ventral expression domain is present in the maxilla, mandible, and antenna. Because of this, the role of H15 in the determination of ventral fate remains unclear.
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| 5. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 6. |
- Shi, Wei, 1970-
(författare)
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Growth and Behaviour : Epigenetic and Genetic Factors Involved in Hybrid Dysgenesis
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In mammals, the most frequently observed hybrid dysgenesis effects are growth disturbances and male sterility. Profound defects in placental development have been described and our work on hybrids in genus Mus has demonstrated putative hybrid dysgenesis effects that lead to defects in lipid homeostasis and maternal behavior. Interestingly, mammalian interspecies hybrids exhibit strong parent-of-origin effects in that offspring of reciprocal matings, even though genetically identical, frequently exhibit reciprocal phenotypes. Recent studies have provided strong link between epigenetic regulation and growth, behavior and placental development. Widespread disruption of genomic imprinting has been described in hybrids between closely related species of the genus Peromyscus. The studies presented in this thesis aim to investigate the effects of disrupted epigenetics states on altered growth, female infanticide and placental dysplasia observed in Mus hybrids. We showed that loss-of-imprinting (LOI) of a paternally expressed gene, Peg1, was correlated with increased body weight of F1 hybrids. Furthermore, we investigated whether LOI of Peg1 in F1 females would interfere with maternal behavior. A subset of F1 females indeed exhibited highly abnormal maternal behavior in that they rapidly attacked and killed the pups. By microarray hybridization, a large number of differentially expressed genes in the infanticidal females as compared to normally behaving females were identified. In addtion to Peg1 LOI, we studied allelic expression of numerous imprinted genes in adult Mus interspecies hybrids. In contrast to the study from Peromyscus, patterns of LOI were not consistent with a direct influence of altered expression levels of imprinted genes on growth. Finally, we investigated the allelic interaction between an X-linked locus and a paternally expressed gene, Peg3, in placental defects in Mus hybrids. This study further strengthened the notion that divergent genetic and epigenetic mechanisms may be involved in hybrid dysgenesis in diverse groups of mammals.
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| 7. |
- Staubach, Fabian, et al.
(författare)
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A test of the neutral model of expression change in natural populations of house mouse subspecies
- 2010
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Ingår i: Evolution. - : Wiley. - 0014-3820 .- 1558-5646. ; 64:2, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Changes in expression of genes are thought to contribute significantly to evolutionary divergence. To study the relative role of selection and neutrality in shaping expression changes, we analyzed 24 genes in three different tissues of the house mouse (Mus musculus). Samples from two natural populations of the subspecies M. m. domesticus and M. m. musculus were investigated using quantitative PCR assays and sequencing of the upstream region. We have developed an approach to quantify expression polymorphism within such populations and to disentangle technical from biological variation in the data. We found a correlation between expression polymorphism within populations and divergence between populations. Furthermore, we found a correlation between expression polymorphism and sequence polymorphism of the respective genes. These data are most easily interpreted within a framework of a predominantly neutral model of gene expression change, where only a fraction of the changes may have been driven by positive selection. Although most genes investigated were expressed in all three tissues analyzed, significant changes of expression levels occurred predominantly in a single tissue only. This adds to the notion that enhancer-specific effects or transregulatory effects can modulate the evolution of gene expression in a tissue-specific way.
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| 8. |
- Tautz, Diethard, et al.
(författare)
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Next generation molecular ecology.
- 2010
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Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 19:Suppl. 1, s. 1-3
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Wolf, Jochen B. W., et al.
(författare)
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Nucleotide divergence vs. gene expression differentiation : comparative transcriptome sequencing in natural isolates from the carrion crow and its hybrid zone with the hooded crow
- 2010
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Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 19:Suppl. 1, s. 162-175
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in sequencing technology promise to provide new strategies for studying population differentiation and speciation phenomena in their earliest phases. We focus here on the black carrion crow (Corvus [corone] corone), which forms a zone of hybridization and overlap with the grey coated hooded crow (Corvus [corone] cornix). However, although these semispecies are taxonomically distinct, previous analyses based on several types of genetic markers did not reveal significant molecular differentiation between them. We here corroborate this result with sequence data obtained from a set of 25 nuclear intronic loci. Thus, the system represents a case of a very early phase of species divergence that requires new molecular approaches for its description. We have therefore generated RNAseq expression profiles using barcoded massively parallel pyrosequencing of brain mRNA from six individuals of the carrion crow and five individuals from a hybrid zone with the hooded crow. We obtained 856 675 reads from two runs, with average read length of 270 nt and coverage of 8.44. Reads were assembled de novo into 19 552 contigs, 70% of which could be assigned to annotated genes in chicken and zebra finch. This resulted in a total of 7637 orthologous genes and a core set of 1301 genes that could be compared across all individuals. We find a clear clustering of expression profiles for the pure carrion crow animals and disperse profiles for the animals from the hybrid zone. These results suggest that gene expression differences may indeed be a sensitive indicator of initial species divergence.
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