DNA sequence variation in a 3.7-kb noncoding sequence 5' of the CYP1A2 gene: implications for human population history and natural selection

CYP1A2 is a cytochrome P450 gene that is involved in human physiological responses to a variety of drugs and toxins. To investigate the role of population history and natural selection in shaping genetic diversity in CYP1A2, we sequenced a 3.7-kb region 5' from CYP1A2 in a diverse collection of 113 individuals from three major continental regions of the Old World (Africa, Asia, and Europe). We also examined sequences in the 90-member National Institutes of Health DNA Polymorphism Discovery Resource (PDR). Eighteen single-nucleotide polymorphisms (SNPs) were found. Most of the high-frequency SNPs found in the Old World sample were also found in the PDR sample. However, six SNPs were detected in the Old World sample but not in the PDR sample, and two SNPs found in the PDR sample were not found in the Old World sample. Most pairs of SNPs were in complete linkage disequilibrium with one another, and there was no indication of a decline of disequilibrium with physical distance in this region. The average +/- SD nucleotide diversity in the Old World sample was 0.00043+/-0.00026. The African population had the highest level of nucleotide diversity and the lowest level of linkage disequilibrium. Two distinct haplotype clusters with broadly overlapping geographical distributions were present. Of the 17 haplotypes found in the Old World sample, 12 were found in the African sample, 8 were found in Indians, 5 were found in non-Indian Asians, and 5 were found in Europeans. Haplotypes found outside Africa were mostly a subset of those found within Africa. These patterns are all consistent with an African origin of modern humans. Seven SNPs were singletons, and the site-frequency spectrum showed a significant departure from neutral expectations, suggesting population expansion and/or natural selection. Comparison with outgroup species showed that four derived SNPs have achieved high (>0.90) frequencies in human populations, a trend consistent with the action of positive natural selection. These patterns have a number of implications for disease-association studies in CYP1A2 and other genes.     

Vitellogenesis by the American cockroach: Electrophoretic and antigenic characterization of haemolymph and oöcyte proteins

Several peptides have been found in the haemolymph which are antigenically similar to peptides found in the terminal oöcyte during vitellogenesis. There appear to be two major peptides. labeled A and D, in the oöcyte with a stoichiometry of A₂D₁. These two proteins are also found in the haemolymph. Several other prominent proteins found in the haemolymph during the six day cycle are not found to be immunochemically similar to yolk antisera.The possibility of a precursor protein found in both the haemolymph and terminal oöcyte with a molecular weight of 189,000 is discussed.     

The Z-band lattice in skeletal muscle in rigor

Previous work with tetanized and relaxed muscle has shown a correlation between active tension and the structure of the Z-band. This suggests that there is a correlation between the cross-bridge binding in the A-band and the structure of the Z-band. Using electron microscopy and optical diffraction we have examined this correlation in glycerinated muscle in rigor and in unstimulated intact muscle. We have found that the Z-bands of muscles in rigor always show the basketweave form, while those of the unstimulated muscles always show the small square form. The basketweave form found in rigor muscles is similar in form and dimension to that found in tetanized muscle. Thus it appears that the small square form of the Z-band is found in physiological states with little cross-bridge binding and the basketweave form is found in states with a high degree of cross-bridge binding.     

Bf and C3 complement types in rheumatoid arthritis

Bf and C3 complement types were studied in 100 male and 100 females patients from northern Sweden with erosive rheumatoid arthritis (RA) and compared with population controls. A significantly decreased frequency of the Bf FS phenotype was found particularly in males and in patients with a family history of polyarthritis. Significant Bf associations were also found with a more severe form of RA (functional classes III and IV) and with high titers of the rheumatoid factor. No significant difference with respect to C3 phenotype and gene frequencies was found between RA patients and controls. Thus, the association between RA and C3F found in some previous investigations was not confirmed.     

Autosomal and sex-chromosomal polymorphism in a wild population of the Norway rat,Rattus norvegicus

The karyotypes of 33 specimens of Rattus norvegicus captured in a wild population, were studied by means of conventional Giemsa staining and G- and C-banding methods. A chromosomal polymorphism for the presence or absence of extra segments in autosomes 3 and 12 and the X chromosome was found, beside a polymorphism for centromeric C-bands in pair no. 6.The frequency of different chromosome types found in this population was compared with that found in a wild population in Japan as well as with that found in some inbred strains.     

Multiple molecular forms of murine thymocyte-stimulating factor

Murine thymocyte stimulating factor (TSF) was found to sediment in sucrose density gradients on a broad band with peaks at about 2.60 S and 2.0 S. Two main peaks of TSF activity (with buoyant densities of 1.34 and 1.28 g/ml) were found in CsCl density gradients. Gel chromatography on Sephadex G-100 columns of the material sedimented in sucrose or CsCl density gradients originated multiple peaks of TSF activity with various molecular weights. Heterogeneity of molecular forms of TSF was also found upon dilution of the factor. The lowest molecular weights found were 4000 and 4700 daltons. When Sephadex fractions containing the low molecular weight material were pooled and rerun on Sephadex columns, molecular species with a wide range of molecular weights were found. Temperature also affects the appearance of the low molecular weight forms of TSF. Most of the experiments presented in this work were carried out with Sephadex-purified TSF. Multiple molecular forms, however, and, in particular, the forms with molecular weights of 4000 and 4700 daltons were found also with TSF-Fraction IIIa, a highly purified preparation of this factor.     

The YARHG domain: an extracellular domain in search of a function

We have identified a new bacterial protein domain that we hypothesise binds to peptidoglycan. This domain is called the YARHG domain after the most highly conserved sequence-segment. The domain is found in the extracellular space and is likely to be composed of four alpha-helices. The domain is found associated with protein kinase domains, suggesting it is associated with signalling in some bacteria. The domain is also found associated with three different families of peptidases. The large number of different domains that are found associated with YARHG suggests that it is a useful functional module that nature has recombined multiple times.     

Position of ultimobranchial body cysts in the human fetal thyroid gland

In a series of 21 human fetal thyroid glands examined histologically in serial sections, seven ultimobranchial body cysts were found. The position of these cysts correlated well with the distribution of calcitonin-containing cells found by previous investigators in the adult thyroid gland. Ultimobranchial body cysts found external to the thyroid lobes may offer a developmental explanation for the paucity of calcitonin found in some adult thyroid glands. The close developmental relationship between the parathyroid gland and the ultimobranchial body could explain the presence of calcitonin found in these glands in some adults.     

Influence of anthropogenic pollution on ostracod assemblages of Amurskii Bay,Sea of Japan

The species composition and distribution of ostracods were investigated at two sites with different pollution levels on the eastern coast of Amurskii Bay within the limits of Vladivostok City. A total of 41 species were found. In all, thirty-eight species (28 of them alive) were found at the first site between Krasnyi and Groznyi capes. Another twenty-seven species were found at a depth of 1.5–3 m in the phytal zone with a diversity of microbiotopes. As the bottom became increasingly silty and the depth increased, the number of species decreased. A total of 25 species (only 15 of them alive) were found at the mouth of the Vtoraya Rechka River, which is heavily polluted by municipal and industrial sewage discharge. No valves of ostracods were found in surface sediments on silts at a depth down to 5.5m. At 4 m, only 2 species were found alive on stones overgrown with Saccharina japonica. At 500 m from a sewage discharge site, few ostracod valves were found that seemed to have died recently. At a distance of over 1 km, an ostracod assemblage typical of the silty substrates of Amurskii Bay was found below a 7 m depth (21 species, 12 of them alive).     

Two types of triplicated alpha-globin loci in humans.

DNA from healthy Malaysian newborns was studied on gene maps after digestion with different restriction endonucleases. Of 65 newborns, two were found to be carriers of two different variants of triplicated alpha-globin loci. In variant no. 1, found in an Malay, the three alpha-globin genes are in an elongated DNA fragment on digestion with Eco RI and Bam HI. The third alpha-globin gene was found in a additional 3.7-kb fragment on digestion with Hpa I, Bgl II and Hind III. In variant no. 2, a new type of triplicated alpha-globin loci, found in a Chinese, the three alpha-globin genes reside in an elongated DNA fragment longer than that of variant no. 1 on digestion with Eco RI and Bam HI. The third alpha-globin gene was found in an additional 4.2-kb fragment on digestion with Hpa I and Hind III. Digestion of this variant DNA with Bg1 II produced an abnormal 16.7-kb fragment in addition to the normal 7.0-kb Bgl-II fragment. The locations of the restriction sites in the two types of triplicated alpha-globin loci are compatible with a mechanism of unequal crossing over following two different modes of misalignment.     

Extraintestinal sporozoites of chicken Eimeria in chickens and turkeys

Oocysts were found in the feces of chickens (recipients) dosed orally with whole blood, liver, lung, or heart homogenates from chickens and turkeys (donors) inoculated 3 and 4 days previously with a mixture of 3.5 X 10(6) oocysts of chicken Eimeria. No oocysts were found in the feces of recipients given spleen homogenates from these same chickens and turkeys and none were found in the feces of recipients given similar material from uninoculated donors. Intracellular sporazoites were found in the peripheral blood of a turkey inoculated with chicken Eimeria. The results indicate that a small number of sporozoites are capable of invading and surviving for at least 4 days in the peripheral blood of chickens and turkeys.     

Co-evolution of the legume-Rhizobium association

Summary A number of examples is given demonstrating the co-existence of pea genotypes and their specific Rhizobium, strains isolated within the same region.R. leguminosarum strains compatible with the cultivated pea have a narrow symbiotic range and they are widely distributed in European soils. This is presumably due to the narrow genetic base of the cultivated pea and its wide-spread cultivation in European soils. Rhizobium strains capable of nodulating a primitive pea line from Afghanistan were only found in soils of the Middle East and Central Asia. A more restricted distribution of specific Rhizobium strains was found for fulvum peas from Israel. Rhizobium strains effective with the fulvum pea were found in Israeli soils. A good example of co-evolution due to geographical isolation was found in south Turkey. Here a pea line was found which can form an effective symbiosis with local Rhizobium strains but not with strains from other parts of Turkey.     

A species of Sarcocystis using owls as definitive hosts.

Sporulated oocysts found in the intestines of a Masked Owl (Tyto novaehollandiae) and a Barn Owl (T. alba) produced sarcocysts in mice. Schizonts were found in the livers of 3 mice that died at 7-8 days after dosing. Neither sarcocysts nor schizonts were found in chickens dosed with oocysts from a Masked Owl.     

Biological properties of rat serum hydrolases splitting N-acetyl-L-tyrosine ethyl ester.

An increase in the level of activity splitting N-acetyl-L-tyrosine ethyl ester (ATEE) was found in the plasma of rats with experimentally induced rheumatoid inflammation. The level of this activity rose paralled with development of the inflammation. Homogenate of inflamed rat paws was found to contain a raised content of the high molecular weight fraction. Which was found to contain a raised content of the fraction I (splitting ATEE) causes an increase in vascular permeability and releases active kinins from plasma kininogens. These properties were also found, on a smaller scale, in serum fraction II. The results show no parallel between ATEE-splitting activity and the magnitude of the biological response.     

Cystathionine beta synthase: gene dosage effect in trisomy 21

The enzymatic activity of cystathionine beta synthase has been studied in fibroblasts of nine patients with regular trisomy 21. An excess of CBS activity was found in trisomy 21 with a trisomy 21/normal ratio equal to 1.66. A 1.04 ratio was found in 21q21----21 p ter monosomy; a 1.04 and 0.99 ratio was found in two 21 qter----21q22.3 monosomies; a 1.14 ratio in 21 qter----21q22 monosomy; a 0.89 ratio in a 21q21----21 pter trisomy; an excess of CBS activity was found in a 21q22.1 ----21q21 trisomy with a 1.57 ratio. These results show a gene dosage effect in human fibroblasts trisomic for chromosome 21 and suggest the assignment of human CBS locus between 21q22.1 and 21q21.     

Med,a cell-surface localized protein regulating a competence transcription factor gene,comK, in Bacillus subtilis

Med was found as a positive regulator for comK, a master regulator for late competence genes. It was found by Western analysis that the ComK level was decreased in a med mutant. Experiments using an alkaline phosphatase fusion with Med and Western analysis of Med were done because a putative lipo-modification signal is found at the N-terminus of Med. The results obtained are consistent with the localization of Med at the cell surface. An implication of the cell-surface localization of Med is discussed in terms of comK regulation.     

Cytoplasmic helical structure associated with Acholeplasma laidlawii.

A distinct spiral protein structure was found in three species of Acholeplasma, but was not found in the Mycoplasma species studied. The spirals, which are 14 nm in width and of variable length from 50 to 300 nm, are formed by a helical arrangement of 7-nm subunits. A rosette-like structure 45 nm in diameter also composed of 7-nm subunits was found in close association with the spirals and may be a taut in vivo form of the spiral. The electrophoretic profile in sodium dodecyl sulfate-polyacrylamide gels indicated that the spirals are composed of a predominant polypeptide with an apparent molecular weight of 100,000. No evidence can be found for inferring actin-like properties for this structure.