uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
2R and remodeling of vertebrate signal transduction engine
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
2010 (English)In: BMC Biology, ISSN 1741-7007, Vol. 8, 146- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Whole genome duplication (WGD) is a special case of gene duplication, observed rarely in animals, where all genes duplicate simultaneously through polyploidisation. Two rounds of WGD (2R-WGD) occurred at the base of vertebrates, giving rise to an enormous wave of genetic novelty, but a systematic analysis of functional consequences of this event has not yet been performed. Results: We show that 2R-WGD affected overwhelming majority (74%) of signaling genes, in particular developmental pathways involving receptor tyrosine kinases, Wnt and TGF-beta ligands, GPCRs, and the apoptosis pathway. 2R-retained genes, in contrast to tandem duplicates, were enriched in protein interaction domains, and multifunctional signaling modules of Ras and MAP-kinase cascades. 2R-WGD had a fundamental impact on the cell-cycle machinery; redefined molecular building blocks of the neuronal synapse; and was formative for vertebrate brains. We investigated 2R-associated nodes in context of the human signaling network, as well as an inferred ancestral pre-2R (AP2R) network, and found that hubs (particularly involving negative regulations), were preferentially retained, with high-connectivity driving retention. Finally, microarrays and proteomics demonstrated a trend for gradual paralog expression divergence, independent of the duplication mechanism; but inferred ancestral expression states suggested preferential sub-functionalisation among 2R-ohnologs (2ROs). Conclusions: The 2R event left an indelible imprint on vertebrate signaling and cell-cycle. We show that 2R-WGD preferentially retained genes are associated with higher organismal complexity (e.g. locomotion, nervous system, morphogenesis), while genes associated with basic cellular functions (e.g. translation, replication, splicing, recombination; with the notable exception of cell-cycle) tended to be excluded. 2R-WGD set the stage for the emergence of key vertebrate functional novelties (such as complex brains, circulatory system, heart, bone, cartilage, musculature, and the adipose tissue). Full explanation of the impact of 2R on evolution, function, and the flow of information in vertebrate signaling networks is likely to have practical consequences for regenerative medicine, stem cell therapies, and cancer treatment.

Place, publisher, year, edition, pages
2010. Vol. 8, 146- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-139280DOI: 10.1186/1741-7007-8-146ISI: 000288535900001PubMedID: 21144020OAI: oai:DiVA.org:uu-139280DiVA: diva2:380897
Available from: 2010-12-22 Created: 2010-12-22 Last updated: 2011-04-06Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Ludwig Institute for Cancer Research
In the same journal
BMC Biology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 147 hits
ReferencesLink to record
Permanent link

Direct link