Nucleotide distribution in gymnosperm nuclear sequences suggests a model for GC-content change in land-plant nuclear genomes

Nuclear protein coding sequences from gymnosperms are currently scarce. We have determined 4 kb of nuclear protein coding sequences from gymnosperms and have collected and analyzed >60 kb of nuclear sequences from gymnosperms and nonspermatophytes in order to better understand processes influencing genome evolution in plants. We show that conifers possess both biased and nonbiased genes with respect to GC content, as found in monocots, suggesting that the common ancestor of conifers and monocots may have possessed both biased and nonbiased genes. The lack of biased genes in dicots is suggested to be a derived character for this lineage. We present a simple but speculative model of land-plant genome evolution which considers changes in GC bias and CpG frequency, respectively, as independent processes and which can account for several puzzling aspects of observed nucleotide frequencies in plant genes.Abbreviations GC guanosine plus cytosine - GapC glycolytic glyceraldehyde-3-phosphate dehydrogenase, EC 1.2.1.12 - GapA Calvin cycle glyceraldehyde-3-phosphate dehydrogenase, EC 1.2.1.13 - O/E ratio of observed-to-expected dinucleotide frequencies Correspondence to: W. Martin     

Mathematical Model For Human Myeloma Relating Growth Kinetics and Drug Resistance

Abstract. We present a computer-based mathematical model that can simulate characteristic features of the clinical time course of human myeloma. It asserts that therapy resistance in myeloma cells is an inherited trait associated with the longer inter-mitotic times of some cells and that the strength of this trait affects tumour growth characteristics. These kinetic differences within the malignant cell clone may also influence therapeutic efficacy. In the model, the same total therapy, administered in different time-dose fractions, could be 'curative' or 'minimally effective' depending on kinetic properties. For example, as others have shown, in myeloma pulsed intermittent therapy is often more effective than low dose continuous therapy. According to our model this finding is compatible with a high coefficient of inheritability of resistance from one cell generation to the next. the model also suggests that if there are subclones of varying resistance, a therapy must have some effect on each of them if it is to be employed in a curative fashion. While many aspects of the model are not yet clinically testable, exploration of its concepts might increase knowledge about fundamental neoplastic mechanisms.