The evolution of developmental programs : a case study in the gastropod mollusc Patella vulgata

At the interface between evolutionary biology and developmental biology is the so-called field of evolutionary developmental biology (evo-devo in short). This field asks how different adult animals (species) came into being by heritable changes during their embryonic development. One way to study this question is a comparative analysis of genes that are important for the development of different species. Many genes appear to be conserved during evolution, i.e. the same gene can have a comparable role during the development of very different species. This developmental genetic unity underlying very different animals has puzzled evolutionists as well as developmental biologists. It has led to two main questions: -what aspects of gene function can be considered as conserved, thus evolutionary very ancient, perhaps even ancestral to metazoans (or bilaterians)? -how can such different animals be generated from such similar sets of genes? This study is involved with the phylum Mollusca (snails, slugs, octopuses and the like). Very little is known on the genetics of early development of molluscs. Data on the role of genes during the development of molluscan animals, therefore, is likely to provide new insights and will contribute to answering the abovementioned questions. The study organism of this thesis is the gastropod mollusk Patella vulgata. Orthologs (gene homologs) of seven genes are described: snail, twist, orthodenticle, orthopedia, engrailed, dpp en hedgehog. The question asked is in this thesis is: what insights do we obtain when we broaden our comparative analysis of the role developmental genes play to molluscs? The research on these seven genes has given a number of new insights. One is a better understanding on what role of these genes has been conserved during evolution. It is very likely that the common evolutionary ancestor to all animals already had these genes with these particular functions. Despite the fact that many animals have genes in common, often with the same function, not all animals are alike. The research described in this thesis contributed to our understanding of this apparent paradox. A gene can have a certain function, which allows it to contribute to the development of very different structures or organs. For example, the engrailed gene is involved in generating boundaries between groups of cells. During development, cells expressing the engrailed gene form a compartment excluding other, neighbouring cells that form another compartment (and do not express engrailed). Both compartments become different parts of the adult organism. In the fruitfly, for example, engrailed plays a role in boundary formation between segments, the building blocks of the body of the fly. But also in molluscs, such as Patella, engrailed is involved in boundary formation, namely between cells that form the shell and the surrounding cells that do not contribute to shell formation. The fact that such very different structures such as segments in flies and shells in snails use the same gene for their formation can thus be explained by the fact that engrailed is a boundary formation gene. This is the way evolution creates different animals from the same set of genes: by recombining similar building blocks in new ways, new structures can be formed, a phenomenon called tinkering (or bricolage)

GSuite HyperBrowser: integrative analysis of dataset collections across the genome and epigenome

Background: Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation. Findings: We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered. Conclusions: Through a combination of streamlined data acquisition, interoperable representation of dataset collections, and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no.This work was supported by the Research Council of Norway (under grant agreements 221580, 218241, and 231217/F20), by the Norwegian Cancer Society (under grant agreements 71220’PR-2006-0433 and 3485238-2013), and by the South-Eastern Norway Regional Health Authority (under grant agreement 2014041).Peer Reviewe

The khmer software package: enabling efficient nucleotide sequence analysis

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

The khmer software package: enabling efficient nucleotide sequence analysis [version 1; referees: 2 approved, 1 approved with reservations]

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

Good enough practices in scientific computing

Computers are now essential in all branches of science, but most researchers are never taught the equivalent of basic lab skills for research computing. As a result, data can get lost, analyses can take much longer than necessary, and researchers are limited in how effectively they can work with software and data. Computing workflows need to follow the same practices as lab projects and notebooks, with organized data, documented steps, and the project structured for reproducibility, but researchers new to computing often don’t know where to start. This paper presents a set of good computing practices that every researcher can adopt, regardless of their current level of computational skill. These practices, which encompass data management, programming, collaborating with colleagues, organizing projects, tracking work, and writing manuscripts, are drawn from a wide variety of published sources from our daily lives and from our work with volunteer organizations that have delivered workshops to over 11,000 people since 2010

Genomic characterization of the Atlantic cod sex-locus

A variety of sex determination mechanisms can be observed in evolutionary divergent teleosts. Sex determination is genetic in Atlantic cod (Gadus morhua), however the genomic location or size of its sex-locus is unknown. Here, we characterize the sex-locus of Atlantic cod using whole genome sequence (WGS) data of 227 wild-caught specimens. Analyzing more than 55 million polymorphic loci, we identify 166 loci that are associated with sex. These loci are located in six distinct regions on five different linkage groups (LG) in the genome. The largest of these regions, an approximately 55 Kb region on LG11, contains the majority of genotypes that segregate closely according to a XX-XY system. Genotypes in this region can be used genetically determine sex, whereas those in the other regions are inconsistently sex-linked. The identified region on LG11 and its surrounding genes have no clear sequence homology with genes or regulatory elements associated with sex-determination or differentiation in other species. The functionality of this sex-locus therefore remains unknown. The WGS strategy used here proved adequate for detecting the small regions associated with sex in this species. Our results highlight the evolutionary flexibility in genomic architecture underlying teleost sex-determination and allow practical applications to genetically sex Atlantic cod

From Green to Red: Horizontal Gene Transfer of the Phycoerythrin Gene Cluster between Planktothrix Strains

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The genomic mosaicism of hybrid speciation

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