The 'effective number of codons' used in a gene

A simple measure is presented that quantifies how far the codon usage of a gene departs from equal usage of synonymous codons. This measure of synonymous codon usage bias, the 'effective number of codons used in a gene', Nc, can be easily calculated from codon usage data alone, and is independent of gene length and amino acid (aa) composition. Nc can take values from 20, in the case of extreme bias where one codon is exclusively used for each aa, to 61 when the use of alternative synonymous codons is equally likely. Nc thus provides an intuitively meaningful measure of the extent of codon preference in a gene. Codon usage patterns across genes can be investigated by the Nc-plot: a plot of Nc vs. G + C content at synonymous sites. Nc-plots are produced for Homo sapiens, Saccharomyces cerevisiae, Escherichia coli, Bacillus subtilis, Dictyostelium discoideum, and Drosophila melanogaster. A FORTRAN77 program written to calculate Nc is available on request.     

Knowledge and experience of young people regarding drug abuse, 1969-89.

OBJECTIVE--To establish a baseline of knowledge to plan an effective health education programme in schools. The survey was repeated at five year intervals from 1969 to 1989. DESIGN--To preserve consistency, the same anonymous questionnaire, which was confidential to the research workers, was used throughout. SETTING--Three secondary schools in Wolverhampton in different parts of the town and representing different social groups. SUBJECTS--Sample sizes ranged from 471 fourth year pupils (aged 14 to 15) in 1969 to 540 in 1984 and 380 in 1989, the decrease being due mainly to the falling birth rate. There were slightly more girls than boys, and the pupils covered the whole range of academic ability. RESULTS--Over the 20 years the proportion of pupils who knew someone taking drugs more than doubled from 15% (71) to 31% (117) and the proportion who had been offered drugs almost quadrupled from 5% (24) to 19% (72). The changes taking place over the past five years were characterised by an increased knowledge about drugs and the first mention of "crack," a purified form of cocaine, and "ecstasy" (methylenedioxymethamphetamine). Peer influence continued to be given as the prime reason for taking drugs. Over the 20 years, though less often mentioned in 1989, television and newspapers remained the most common source of information. CONCLUSIONS--These results suggest the need for responsible coverage by the mass media and for more effective health and social education programmes to prevent the spread of drug misuse.     

Diffusion gradient plates for herbicide toxicity tests on micro-algae and cyanobacteria

Single dimension agar gel diffusion gradient plates were used to test the tolerance of several micro-algae and cyanobacteria to five herbicides. Growth of most of the test organisms was prevented by terbutryn and diuron at concentrations between 1·1 and 2·8 μg/ml (minimum inhibitory concentration, MIC). Chlorpropham was intermediate in toxicity whilst monuron and atrazine generally gave higher MIC values (up to 17·1 μg/ml). The cyanobacteria were mostly more tolerant than the algae, but susceptibility to the herbicides was variable even between strains of an individual algal species. The gradient plate technique offers the advantages of simplicity and low cost in toxicity screening studies with herbicides or other biologically active chemicals and xenobiotics.     

Codon usage patterns in Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens; a review of the considerable within-species diversity.

The genetic code is degenerate, but alternative synonymous codons are generally not used with equal frequency. Since the pioneering work of Grantham's group it has been apparent that genes from one species often share similarities in codon frequency; under the "genome hypothesis" there is a species-specific pattern to codon usage. However, it has become clear that in most species there are also considerable differences among genes. Multivariate analyses have revealed that in each species so far examined there is a single major trend in codon usage among genes, usually from highly biased to more nearly even usage of synonymous codons. Thus, to represent the codon usage pattern of an organism it is not sufficient to sum over all genes as this conceals the underlying heterogeneity. Rather, it is necessary to describe the trend among genes seen in that species. We illustrate these trends for six species where codon usage has been examined in detail, by presenting the pooled codon usage for the 10% of genes at either end of the major trend. Closely-related organisms have similar patterns of codon usage, and so the six species in Table 1 are representative of wider groups. For example, with respect to codon usage, Salmonella typhimurium closely resembles E. coli, while all mammalian species so far examined (principally mouse, rat and cow) largely resemble humans.     

The Upper Cave at Zhoukoudian and the origins of the Mongoloids

The best evidence for identifying the inhabitants of northeast Asia in the terminal Pleistocene or early Holocene periods is provided by the human burials from the Upper Cave at Zhoukoudian, and in particular the “Old Man”. Apart from the Minatogawa finds on Okinawa, all Late Pleistocene human remains from East Asia that are reasonably well published are poorly preserved and often have equivocal dates. Since the time the Upper Cave was excavated it has been supposed that the human remains were the link between “Peking Man” and the modern Mongoloid complex. We have carried out multivariate analyses of the “Old Man” cranium employing new measurements of Weidenreich's cast of the skull and comparative data from Howells' survey of modern human groups. Despite our expectations the analyses have not shown the “Old Man” to be closely linked with the Mongoloids. Considering all the evidence available we conclude that the common belief of a close biological relationship between the people buried in the Upper Cave and the modern Mongoloids is not yet adequately demonstrated. Of crucial importance in interpreting the Upper Cave burials is their antiquity, which is still commonly thought to be in the order of at least 18 000 years. We believe that recent C-14 dates of about 11 000 years, determined from animal bones, indicate the earliest possible date for the burials. The time span between the Upper Cave burials and the earliest known modern Mongoloids in north China is in the order of about 4–5000 years. It is possible that a major population shift has occurred in north China between the terminal Pleistocene and the mid Holocene, when farming first appears. If this is so, the Upper Cave people may not have been closely allied to the Mongoloid groups that now inhabit East Asia and the Americas.     

Short estrous cycles and associated progesterone in serum of beef heifers aborted at various stages of gestation

Estrous cycles were observed and concentrations of progesterone were measured after abortion in crossbred Angus heifers that were injected with a prostaglandin F(2) alpha analogue about day 50 (15 heifers), 75 (14 heifers), 100 (13 heifers) or 125 (49 heifers) of gestation. The average interval from injection to first estrus was 3.6, 4.2, 3.7 and 6.4 d for heifers injected at an average of 50, 75, 100 or 125 d of gestation, respectively. Cycles of fewer than 13 d were classified as short, those of 13 to 16 d as intermediate, those of 16 to 24 d as normal, and those of more than 24 d as long. Heifers aborted at 50 d of gestation had seven short and eight normal first cycles; heifers aborted at 75 d had 11 short cycles, two normal cycles, and one long cycle; heifers aborted at 100 d had 12 short cycles and one normal cycle; whereas heifers aborted at 125 d had 25 short cycles, 13 normal cycles, two long cycles, six intermediate cycles. Three heifers failed to exhibit a second estrus by 50 d after abortion. Of those heifers having short first cycles, short second cycles occurred in one of seven heifers aborted at Day 50, three of 11 at Day 75, seven of 12 at Day 100 and 18 of 25 at Day 125. Serum progesterone was measured at 0, 1 and 2 d after injection and at 5 and 10 d after the first estrus. Concentration of progesterone in serum declined before estrus, then increased by 5 d after estrus in all cases. Progesterone concentration increased between 5 and 10 d after estrus in heifers exhibiting normal estrous cycles but docreased in heifers having short cycles. Data indicate that the percentage of heifers having single or repeated short cycles after abortion increases as the duration of gestation increases to 100 d.     

Cold culture of different stage mouse embryos in bicarbonated and bicarbonate-free media

Mouse embryos of different stages of development were cultured to expanded blastocysts following storage (1 to 8 d) at 4 degrees C in the presence or absence of HCO(3)(-). The effect of oxygen tension on the cold storage of one- and two-cell mouse embryos at 4 degrees C was evaluated by 37 degrees C culture and transfer to pseudopregnant recipients. Survival at 4 degrees C of early, one- to four-cell mouse embryos was improved with HCO(3)(-) in the medium. The presence of HCO(3)(-) was not of benefit for morulae or blastocyst survival following cold storage. Reducing the oxygen atmosphere from 20 to 5% O(2) improved survival of one-cell mouse embryos stored at 4 degrees C. The survival of two- and four-cell embryos, morulae and blastocysts at 4 degrees C was similar in 90% N(2), 5% CO(2) and 5% CO(2) in air, but it was significantly poorer in air alone. The collapse of morulae and blastocysts during cold storage up to 5 d was reduced with HCO(3)(-) in the storage medium. Blastocysts stored for 6 d at 4 degrees C failed to survive following immediate transfer to pseudopregnant recipients. Blastocyst survival was improved compared to controls (direct transfer of unstored blastocysts to recipients) when cultured for 36 h at 37 degrees C following 6 d of cold storage. This result suggests that cold-stored mouse blastocysts may require a metabolic period of readjustment to survive following transfer to synchronized recipients.