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Gene expression in chromosomal Ridge domains : influence on transcription, mRNA stability, codon usage, and evolution - Stellingen

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Gene expression in chromosomal Ridge domains : influence on transcription,

mRNA stability, codon usage, and evolution

Gierman, H.J.

Publication date

2010

Link to publication

Citation for published version (APA):

Gierman, H. J. (2010). Gene expression in chromosomal Ridge domains : influence on

transcription, mRNA stability, codon usage, and evolution.

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Propositions

1. Anti-Ridges preceded and facilitated the creation of Ridges.

2. The underlying mechanism of low gene expression in anti-Ridges is not restricted to the lack of a Ridge mechanism.

3. Chromosomal domains have contributed to the origin and evolution of vertebrate animals during and after the Cambrian explosion.

4. The recent discovery of Ridges in birds (Nie et al., BMC Genomics. 2010;11:28), not only suggests that dinosaurs (from which birds descend) possessed Ridges, but that Ridges facilitated the evolution of their extreme dimensions: Large predators like Tyrannosaurus rex would have had relatively small population sizes, which strongly reduces the force of natural selection, for which Ridges might compensate.

5. The strong effect of temperature on CpG mutation rate (Fryxell & Zuckerkandl, Mol Biol Evol. 2000;17:1371-83), predicts that the exterior placement of the scrotum prevents the extremization of the isochore structure, due to its cooling effect on germline cells.

6. Aging and cancer are both caused by the deregulation of gene expression: Aging is the random deregulation of genes impairing regenerative growth and cellular function in general, whereas cancer arises whenever random deregulation affects specific genes that facilitate proliferation.

7. Given that RNA is an obvious candidate for specific DNA binding, but that only few examples of RNA-DNA hybrids are known (e.g. Xist), either undiscovered mechanisms prevent the thousands of transcribed RNAs from binding to DNA, or RNA-DNA hybrids are themselves a still largely undiscovered mechanism.

8. The poor detection limit of current protein sequencing methods impedes the high-throughput identification of proteins. In theory, a single protein molecule can be identified by using recombinant aminoacyl tRNA

synthetases to connect the protein's (dissociated) amino acids to corresponding tRNAs: Reverse transcription and single molecule sequencing of the isolated tRNAscan reveal the amino acid composition, which uniquely identifies each protein.

9. The most likely way for malaria to be cured, is if global warming were to bring it to Europe and North America. 10. Evolution without Ridges is like a blind mechanic with a gun shooting at the engine of a car to make it run faster:

Eventually, a bullet will improve the engine by accident, but it takes a couple of billion cars to get there.

11. Evolution with Ridges is like a blind mechanic with a screwdriver and a wrench randomly moving around parts in the engine: Odds are this mechanic will be home a lot earlier.

Propositions belonging to the thesis 'Gene expression in chromosomal Ridge domains. Influence on transcription, mRNA stability, codon usage, and evolution'. Hinco J. Gierman, Amsterdam, April 27th, 2010.

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