A statistical analysis of nucleotide sequences of introns and exons in human genes

DNA sequences of 56 human genes for which information on both exons and introns was available were examined. The variance in G+C content among genes is estimated and shown to be substantial. There is a high correlation in G+C content between exons and introns within the same gene. The dinucleotide frequencies of introns are similar to those of intergenic spacer regions and are in reasonable agreement with predictions from substitution rates estimated from pseudogenes, except that the observed deficiency of TA doublets is not predicted. Duplicated bases also show a frequency greater than the expectation under independence. There is marked variability among genes in the frequency of the doublet CG relative to its expectation under independence. This variation is evolutionarily conserved and is correlated with the G+C content. Pseudogenes behave as if they are in a low -G+C, CG-deficient part of the genome, although the genes from which they arose are variable in these respects.      

Cryptococcus neoformans: Comparisons of in vitro antifungal susceptibilities of serotypes AD and BC

Thirty-nine isolates of Cryptococcus neoformans, nineteen serotype AD and twenty serotype BC, were assayed for susceptibility to eight antifungal agents using an in vitro agar dilution assay. Media employed were Kimmig agar and yeast nitrogen base supplemented with 10% glucose. The antifungal agents used were ketoconazole, amphotericin B, 5-fluorocytosine, nystatin, miconazole, BAY N 7133, ICI 153,066, and itraconazole. No clinically significant differences in in vitro minimum inhibitory concentrations were detected between serotypes AD and BC against any of the compounds tested. An adverse medium effect was observed in two of the assays, but the outcome of the AD/BC comparison was not affected. This is the first report in which the in vitro antifungal susceptibilities of Cryptococcus neoformans serotypes are analyzed.     

Models for the evolution of protandry in insects

Protandry is the tendency for males to emerge before females, and it is common in insects with discrete, nonoverlapping generations in which females mate once only soon after emergence. In these circumstances males which emerge early will have more opportunities to mate than those which emerge late, so that protandry would be expected to evolve through sexual selection. In diploid species in which the primary sex ratio is fixed, protandry can evolve only through shortening the developmental time of males, so changing the distribution of their emergence times. Two models of the evolution of protandry in this way are compared. The first model assumes that the distribution of male emergence times can respond without any constraint to sexual selection, so leading to an “ideal free” distribution; the second model assumes that the distribution can shift only in mean (or possibly in mean and variance), but not in shape.     

Cryptococcus neoformans II. Phagocytosis by Human Leukocytes

Twenty-four per cent of the leukocytes from healthy human subjects phagocytized an encapsulated strain of Cryptococcus neoformans. Phagocytosis was approximately three times more effective with nonencapsulated mutants of C. neoformans. When the mutants reverted to the encapsulated state, the percentages of phagocytosis decreased. These data indicate that cryptococcal polysaccharide inhibits the phagocytosis of C. neoformans by human leukocytes.     

Reduced synonymous substitution rate at the start of enterobacterial genes.

Synonymous codon usage is less biased at the start of Escherichia coli genes than elsewhere. The rate of synonymous substitution between E.coli and Salmonella typhimurium is substantially reduced near the start of the gene, which suggests the presence of an additional selection pressure which competes with the selection for codons which are most rapidly translated. Possible competing sources of selection are the presence of secondary ribosome binding sites downstream from the start codon, the avoidance of mRNA secondary structure near the start of the gene and the use of sub-optimal codons to regulate gene expression. We provide evidence against the last of these possibilities. We also show that there is a decrease in the frequency of A, and an increase in the frequency of G along the E.coli genes at all three codon positions. We argue that these results are most consistent with selection to avoid mRNA secondary structure.     

Computer-based simulation of the recovery of intracellular enzymes and its pilot-scale verification

Accurate and reliable models are required for a range of unit operations if simulations are to be used for accelerating the design and optimisation of bioprocesses. This paper presents results of pilot-plant studies that have been used to verify process simulations for a sequence of operations comprising of cell disruption, fractional protein precipitation and centrifugal separation. These have been tested using the purification of the enzyme alcohol dehydrogenase (ADH) from Saccharomyces cerevisiae as being representative of the recovery of a labile intracellular enzyme. Comparison of pilot-plant against simulated data highlights where improvements to the models are required and has resulted in increased confidence in the simulations for a wide range of conditions including the operational scale and the nature of the starting material. Results demonstrate the effectiveness of the verification approach for the development of reliable predictive models to assess the feasibility of process designs and performance of a train of bioprocess operations. UCL is the Biotechnology and Biological Sciences Research Council's sponsored Advanced Centre for Biochemical Engineering and the Council's support is gratefully acknowledged. The authors would like to thank I Ms. N. Abidi for technical assistance.     

Strand symmetry of mutation rates in theβ-globin region

Summary It has been suggested that there may be inequalities in the types of substitution on the two DNA strands (in particular, in the frequencies of transversions from R to Y and from Y to R) due to a higher error rate on the lagging than the leading strand during replication. Reexamination of 11 kb of the -globin region sequenced in six primates fails to confirm this suggestion. Examination of the 73-kb -globin region sequenced in humans shows that the frequency of pyrimidines in different parts of this region is more variable than expected in a random sequence, but the pattern is more consistent with nonrandomness generated by DNA turnover mechanisms than with strand asymmetry due to a higher error rate on the lagging strand.     

Fascioloides magna (Bassi, 1875) in feral swine from southern Texas.

Between 1971 and 1975, Fascioloides magna was found in 46 of 67 (69%) feral swine (Sus scrofa) in southern Texas. Flukes were recovered from swine in areas where F. magna commonly has been recovered from white-tailed deer and cattle. One to 12 flukes were recovered from each infected animal. Their presence was indicated by black hematin pigment on the liver and various other internal organs. Eggs were not detected in the gallbladder or feces of infected animals although mature flukes and eggs were recovered in the livers suggesting that, like cattle, feral swine can be infected but are aberrant hosts for the parasite and do not disseminate eggs.     

Enzymes for biosynthesis de novo and elongation of fatty acids in mycobacteria grown in host cells: is Mycobacterium leprae competent in fatty acid biosynthesis?

Fatty acid synthetase activity in extracts of Mycobacterium leprae was equivalent to 1.7 pmol malonyl-CoA incorporated into fatty acid min-1 (mg protein)-1. This activity--if representative of living M. leprae organisms--is insufficient to enable them to synthesize their lipid requirements rapidly enough to support growth. The major activity for scavenging fatty acids in extracts of Mycobacterium microti and Mycobacterium avium, as well as in extracts of M. leprae, was acetyl-CoA-dependent fatty acyl-CoA 'elongase'. This activity was about four times higher in M. avium and M. microti grown in a medium which contained lipids, or when grown in mice, than in medium without added lipids. In contrast, the de novo fatty acid synthetase activity was repressed in M. avium and M. microti when grown in medium that contained lipids, or when grown in mice. These results are consistent with the hypothesis that mycobacteria grown in vivo preferentially scavenge lipids from the host cells, and suggest that a source of lipid should be included in media for attempted axenic isolation of M. leprae.     

Synonymous Substitution Rates in Enterobacteria

It has been shown previously that the synonymous substitution rate between Escherichia coli and Salmonella typhimurium is lower in highly than in weakly expressed genes, and it has been suggested that this is due to stronger selection for translational efficiency in highly expressed genes as reflected in their greater codon usage bias. This hypothesis is tested here by comparing the substitution rate in codon families with different patterns of synonymous codon use. It is shown that the decline in the substitution rate across expression levels is as great for codon families that do not appear to be subject to selection for translational efficiency as for those that are. This implies that selection on translational efficiency is not responsible for the decline in the substitution rate across genes. It is argued that the most likely explanation for this decline is a decrease in the mutation rate. It is also shown that a simple evolutionary model in which synonymous codon use is determined by a balance between mutation, selection for an optimal codon, and genetic drift predicts that selection should have little effect on the substitution rate in the present case.