Sequence of the small subunit ribosomal RNA gene expressed in the bloodstream stages of Plasmodium berghei: evolutionary implications

We have determined the complete nucleotide sequence of the coding region of the small subunit rRNA gene expressed by bloodstream stages of the apicomplexan Plasmodium berghei. It is 2059 nucleotides long. Elements contributing to its relatively large size are all concentrated in regions known to be variable in length among eukaryotes. In a phylogenetic tree constructed from pairwise comparisons of eukaryotic small subunit rRNA sequences, the apicomplexan line branches at a rather early point in eukaryotic evolution before any multicellular kingdoms had yet appeared.     

Power to detect risk alleles using genome-wide tag SNP panels

Advances in high-throughput genotyping and the International HapMap Project have enabled association studies at the whole-genome level. We have constructed whole-genome genotyping panels of over 550,000 (HumanHap550) and 650,000 (HumanHap650Y) SNP loci by choosing tag SNPs from all populations genotyped by the International HapMap Project. These panels also contain additional SNP content in regions that have historically been overrepresented in diseases, such as nonsynonymous sites, the MHC region, copy number variant regions and mitochondrial DNA. We estimate that the tag SNP loci in these panels cover the majority of all common variation in the genome as measured by coverage of both all common HapMap SNPs and an independent set of SNPs derived from complete resequencing of genes obtained from SeattleSNPs. We also estimate that, given a sample size of 1,000 cases and 1,000 controls, these panels have the power to detect single disease loci of moderate risk (λ ~ 1.8–2.0). Relative risks as low as λ ~ 1.1–1.3 can be detected using 10,000 cases and 10,000 controls depending on the sample population and disease model. If multiple loci are involved, the power increases significantly to detect at least one locus such that relative risks 20%–35% lower can be detected with 80% power if between two and four independent loci are involved. Although our SNP selection was based on HapMap data, which is a subset of all common SNPs, these panels effectively capture the majority of all common variation and provide high power to detect risk alleles that are not represented in the HapMap data.     

Plasticity in thermal tolerance has limited potential to buffer ectotherms from global warming

Global warming is increasing the overheating risk for many organisms, though the potential for plasticity in thermal tolerance to mitigate this risk is largely unknown. In part, this shortcoming stems from a lack of knowledge about global and taxonomic patterns of variation in tolerance plasticity. To address this critical issue, we test leading hypotheses for broad-scale variation in ectotherm tolerance plasticity using a dataset that includes vertebrate and invertebrate taxa from terrestrial, freshwater and marine habitats. Contrary to expectation, plasticity in heat tolerance was unrelated to latitude or thermal seasonality. However, plasticity in cold tolerance is associated with thermal seasonality in some habitat types. In addition, aquatic taxa have approximately twice the plasticity of terrestrial taxa. Based on the observed patterns of variation in tolerance plasticity, we propose that limited potential for behavioural plasticity (i.e. behavioural thermoregulation) favours the evolution of greater plasticity in physiological traits, consistent with the ‘Bogert effect’. Finally, we find that all ectotherms have relatively low acclimation in thermal tolerance and demonstrate that overheating risk will be minimally reduced by acclimation in even the most plastic groups. Our analysis indicates that behavioural and evolutionary mechanisms will be critical in allowing ectotherms to buffer themselves from extreme temperatures.     

The fully-active nature of synthetic and hydrolytic activities of glucose-6-phosphatase of intact nuclear membrane

Carbamyl-P: glucose phosphotransferase, mannose-6-P: glucose phosphotransferase, and mannose-6-P and glucose-6-P phosphohydrolase activities of D-glucose-6-P phosphohydrolase (EC 3.1.3.9) have been demonstrated in avian and mammalian liver (and kidney) nuclear membrane. In marked contrast with activities of this enzyme of fragmented endoplasmic reticulum (“microsomes”), those of the intact membrane of isolated nuclei are totally, or nearly-totally, manifest without the need for preliminary activation by detergents or similar treatments. Disruption of nuclei and isolation of nuclear membranes results in the acquisition of detergent-sensitivity of such activities. Physiological implications of these observations are discussed.     

Non-snRNP U1A levels decrease during mammalian B-cell differentiation and release the IgM secretory poly(A) site from repression

A regulated shift from the production of membrane to secretory forms of Immunoglobulin M (IgM) mRNA occurs during B cell differentiation due to the activation of an upstream secretory poly(A) site. U1A plays a key role in inhibiting the expression of the secretory poly(A) site by inhibiting both cleavage at the poly(A) site and subsequent poly(A) tail addition. However, how the inhibitory effect of U1A is alleviated in differentiated cells, which express the secretory poly(A) site, is not known. Using B cell lines representing different stages of B cell differentiation, we show that the amount of U1A available to inhibit the secretory poly(A) site is reduced in differentiated cells. Undifferentiated B cells have more total U1A than differentiated cells and a greater proportion of this is not associated with the U1snRNP. We show that this is available to inhibit poly(A) addition at the secretory poly(A) site using cold competitor RNA oligos to de-repress poly(A) addition in nuclear extracts from the respective cell lines. In addition, endogenous non-snRNP associated U1A-immunopurified from the different cell lines-inhibits poly(A) polymerase activity proportional to U1A recovered, suggesting that available U1A level alone is responsible for changes in its inhibitory effect at the secretory IgM poly (A) site.