(Icelandic) Er hægt að endurlífga útdauð dýr?

Arnar Pálsson, 17/08/2018

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(Icelandic) Er hægt að klóna apa?

Arnar Pálsson, 02/05/2018

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(Icelandic) Hversu mörg gen fáum við frá hverjum forföður?

Arnar Pálsson, 03/04/2018

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Differential gene expression during early development in recently evolved and sympatric Arctic charr morphs

Arnar Pálsson, 29/01/2018

Differential gene expression during early development in recently evolved and sympatric Arctic charr morphs.

Jóhannes Guðbrandsson, Sigríður Rut Franzdóttir, Bjarni Kristófer Kristjánsson, Ehsan Pashay Ahi, Valerie Helene Maier, Kalina H. Kapralova, Sigurður Sveinn Snorrason, Zophonías Oddur Jónsson, Arnar Pálsson

Published in PeerJ.

Phenotypic differences between closely related taxa or populations can arise through genetic variation or be environmentally induced, leading to altered transcription of genes during development. Comparative developmental studies of closely related species or variable populations within species can help to elucidate the molecular mechanisms related to evolutionary divergence and speciation. Studies of Arctic charr (Salvelinus alpinus) and related salmonids have revealed considerable phenotypic variation among populations and in Arctic charr many cases of extensive variation within lakes (resource polymorphism) have been recorded. One example is the four Arctic charr morphs in the ∼10,000 year old Lake Thingvallavatn, which differ in numerous morphological and life history traits. We set out to investigate the molecular and developmental roots of this polymorphism by studying gene expression in embryos of three of the morphs reared in a common garden set-up. We performed RNA-sequencing, de-novo transcriptome assembly and compared gene expression among morphs during an important timeframe in early development, i.e., preceding the formation of key trophic structures. Expectedly, developmental time was the predominant explanatory variable. As the data were affected by some form of RNA-degradation even though all samples passed quality control testing, an estimate of 3 0 -bias was the second most common explanatory variable. Importantly, morph, both as an independent variable and as interaction with developmental time, affected the expression of numerous transcripts. Transcripts with morph effect, separated the three morphs at the expression level, with the two benthic morphs being more similar. However, Gene Ontology analyses did not reveal clear functional enrichment of transcripts between groups. Verification via qPCR confirmed differential expression of several genes between the morphs, including regulatory genes such as AT-Rich Interaction Domain 4A (arid4a) and translin (tsn). The data are consistent with a scenario where genetic divergence has contributed to differential expression of multiple genes and systems during early development of these sympatric Arctic charr morphs.

Trancriptional co-option, transcriptional decay and the principles of regulatory evolution.

Arnar Pálsson, 19/01/2018

Trancriptional co-option, transcriptional decay and the principles of regulatory evolution.

Arnar Pálsson, Institute of biology, University of Iceland

Marcos A. Antezana, Institute of biology, University of Iceland

PALSSON A. & ANTEZANA M. 2017: Transcriptional co-option, transcriptional decay and the principles of regulatory evolution. Abstract. - In: W ERTH S. & O BERMAYER W. (editors). Lichen Genomics Workshop II. Institute of Plant Sciences, University of Graz, Austria. 2–5 November 2017. - Fritschiana (Graz) 85: 32–34. - ISSN 1024-0306.

Regulatory evolution is important for adaptive evolution and the emergence of novelties, in part because regulatory mutations tend to be less pleiotropic than changes in exons. The functional properties of regulatory elements, e.g. short, degenerate motifs, for multiple activators and repressors, dictate the evolution of regulatory DNA (Wray et al. 2003). Stabilizing selection on transcription may explain the evolutionary turnover of transcription factor binding sites (TFBS) in enhancers (Ludwig et al. 2000). Genes have been recruited for multiple functions during evolution, by a process called transcriptional co-option (TC) (True and Carroll 2002). In TC a mutation in a gene (here called focal gene), not previously expressed in a specific tissue or cell population during development, turns the gene on in that tissue and the responsible allele is fixed in the population. As new TFBS arise easily via mutation, it was proposed that any transcription factor can co-opt (influence the transcription of) any gene in the genome (Prud’homme et al 2007). Here we define the opposite scenario, evolution by transcriptional decay (TD). In TD, a mutation reducing strongly the transcription of a focal gene in tissue or developmentally specific fashion is fixed by positive selection. An example of TC would be the recruitment of various crystallins to the vertebrate lens (Piatigorsky 2006), and of TD the loss of Pitx1 expression in pelvic structures in stickleback (Shapiro et al. 2004). Here we will use transcriptional decay and co-option as a prism to explore the principles of regulatory evolution.

 

TC or TD can arise by mutations in either trans-factors (TF) or cis-elements (figure part A). While we focus on mutations in cis, changes in the structure or tissue specific concentration of a TF can affect expression of a focal gene. Such changes are expected to be pleiotropic, with changes in expression of targets of that TF (if changes are in TF level, then the effects will be more circumscribed). Changes at the level of cis-elements will be less pleiotropic. Disruption of TFBS can for example either increase or decrease expression of the focal gene, depending on whether the TF that binds that TFBS represses or activates transcription. The complementary argument applies for mutations that generate TFBS; TC can occur by gain of an activator binding site affecting the focal gene. And in TD a gain of a binding site for repressor near the focal gene.

Regulatory mutations can be pleiotropic. In one scenario, a mutation alters the expression of two or more genes in the same chromosome region. If the fitness increase of the increased expression of the focal gene outweighs the fitness reduction of its chromosome neighbors (figure, part B), then TC can occur. The stronger the selection, the more serious the regulatory side effects can be. After fixation of such a mutation, we anticipate rounds of refinement where the deleterious expression of nearby genes will be alleviated, e.g. by loss of activator sites or gain of repressor sites (figure, part B). Other regulatory changes (miRNA binding sites, RNA degradation etc) may play a role, and the complementary case when reduced expression of two or more genes is favored will adhere to the same principles. Similar mechanistic and evolutionary logic will also be apply if adaptive expression increase of a focal gene in a tissue, leads to increased expression of the gene in other tissues.

The central principles discussed here are, i) mutations disrupting TFBS can lead to beneficial changes in gene expression, ii) cis-regulatory mutations can be pleiotropic, affecting multiple genes and potentially tissues, iii) the likelihood of fixation of such pleiotropic mutations depends on the strength of selection, iv) natural selection is likely to alleviate such side-effects by favoring modifiers (e.g. in cis or trans). Finally, these principles are likely to apply more generally, to gain and decay of associations between trans-regulators and regulatory motifs in DNA, RNA and proteins. For instance regulatory systems like those controlling mRNA splicing, export, stability and localization, translation, protein maturation and modifications and other cellular regulatory cascades.

Acknowledgements. We thank Silke Werth and other organizers of the Lichen Genomics Workshop.

References

Wray G.A., Hahn M.W., Abouheif E., Balhoff J.P., Pizer M., Rockman M.V., Romano L.A. 2003: The evolution of transcriptional regulation in eukaryotes. Molecular Biology and Evolution.20: 1377-1419.

Ludwig M.Z., Bergman C., Patel N.H., Kreitman M. 2000: Evidence for stabilizing selection in a eukaryotic enhancer element. Nature. 403: 564-567.

True J.R., Carroll S.B. 2002 Gene co-option in physiological and morphological evolution. Annual Review Cellular and Developmental Biology. 18: 53-80.

Prud'homme B., Gompel N., Carroll S.B. 2007 Emerging principles of regulatory evolution. Proceedings of the National Academy of Sciences U S A. 15: 8605-8612.

Piatigorsky J. 2006 Evolutionary genetics: seeing the light: the role of inherited developmental cascades in the origins of vertebrate lenses and their crystallins. Heredity. 96: 275-277.

Shapiro M.D., Marks M.E., Peichel C.L., Blackman B.K., Nereng K.S., Jónsson B., Schluter D., Kingsley D.M. 2004 Genetic and developmental basis of evolutionary pelvic reduction in threespine sticklebacks. Nature. 428: 717-723

Differential gene expression during early development in recently evolved and sympatric Arctic charr morphs

Arnar Pálsson, 29/09/2017

Sent to a PeerJ near you.

Differential gene expression during early development in recently evolved and sympatric Arctic charr morphs

Jóhannes Guðbrandsson, Sigríður Rut Franzdóttir, Bjarni Kristófer Kristjánsson, Ehsan Pashay Ahi, Valerie Helene Maier, Sigurður Sveinn Snorrason, Zophonías Oddur Jónsson, Arnar Pálsson

Phenotypic differences between closely related taxa or populations can arise through genetic variation or be environmentally induced, in both cases leading to altered transcription of genes during the structural and functional development of the body. Comparative developmental studies of closely related species or variable populations of the same species can help to elucidate the molecular mechanisms related to population divergence and speciation. Studies of Arctic charr (Salvelinus alpinus) and related salmonids have revealed considerable phenotypic variation among populations and in Arctic charr many cases of extensive variation within lakes (resource polymorphism) have been recorded. One example is the four Arctic charr morphs in the ~10.000 year old Lake Thingvallavatn, which differ in numerous morphologicaland life history traits. We set out to investigate the molecular and developmental roots of this polymorphism by studying gene expression in embryos of three of the morphs reared in a common garden set-up. We performed RNA-sequencing, de-novo transcriptome assembly and compared gene expression among morphs during a timeframe in early development.

Expectedly, developmental time was the predominant explanatory variable. As the data were affected by RNA-degradation, an estimate of 3’-bias was the second most common explanatory variable. Morph, both as a independent variable and as interaction with developmental time, affected the expression of numerous transcripts. The majority of transcripts with significant morph effects separated the limnetic and the benthic morphs. However, gene ontology analyses did not reveal clear functional enrichment of transcripts between groups. Verification via qPCR confirmed differential expression of several genes between the morphs, including regulatory genes such as Arid4a and Tsn. The data are consistent with a scenario where genetic divergence has contributed to differential expression of multiple genes and systems during early development of these sympatric Arctic charr morphs.

(Icelandic) Geta tveir einstaklingar farið í erfðapróf og fengið að vita hvort þeir séu samfeðra?

Arnar Pálsson, 19/09/2017

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(Icelandic) Tilnefningar óskast, fyrir heiðursverðlaun líffræðifélagsins

Arnar Pálsson, 22/08/2017

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Nordic Committee on Bioethics Conference: Facing Death - End of life decisions

Arnar Pálsson, 15/08/2017

Nordic Committee on Bioethics Conference: Facing Death - End of life decisions

Should end of life care for incurable ill patients include the possibility of euthanasia or physician-assisted suicide? Assisted death or euthanasia are not allowed in any of the Nordic countries, however, surveys show that an increased proportion of the public supports this.

The Nordic committee on bioethics will host a conference on address how the Nordic countries can learn from the experience on assisted death in Europe and North America. The conference aims to reach medical professionals, policy makers and academics, and will be organised in cooperation with the Centre for Ethics at the University of Iceland. The conference will take place at the University of Iceland, Veröld, hús Vigdísar, Brynjólfsgata 1, Reykjavík (main auditorium).

Full schedule and registration info.

Session on bioethics at NeIC 2017

Arnar Pálsson, 09/05/2017

For the past 4 years I have served on the Nordic committee for bioethics. The committee operates under the umbrella of Nordforsk, and its mandate is to foster discussion and debate about bioethical questions and topics of relevance to the nordic countries.

Later this month will the committee host a workshop at the NeIC (Nordic electronic infrastructure collaboration) conference in Umea (May 29-June 1). The topics of the workshop are:

"New technologies enable the accumulation of large amounts of genetic data, biometric data, health records and socio-economic data about individuals. These data are increasingly being gathered and mined by companies for research and commercial purposes. The proper handling, security and use of such data is important to protect individuals while enabling the use of the data for the benefits of society, research or business. This workshop aims to investigate key ethical and societal issues concerning the large-scale collection, storage and sharing of data about individuals."

Full schedule of talks is available at the website of the conference.

Bioethics of Databanks and Datasharing