Frequency dependent selection: I. Rare male phenomenon in D. subobscura dependent on the proportion of Amy genotypes and substrate composition

Analysis of the rare male mating advantage in D. subobscura, as a type of frequency dependent selection on maltose and starch media, was done by applying different statistical approaches (χ², cross-product ratio, variance and regression analysis). They reveal that mating occurs at random when proportions of prospective mates are equal, and that mating success of the males homozygous for Amy-locus genotypes (S/S and F/F) depends on their proportion. Regression analysis showed that the F/F males are sexually more active (have higher vigour) than S/S males. Rare male effect is one-sided and appears in F/F males that partake in more heterogamic matings. Comparison of the number of observed and expected homo- and heterogamic matings shows that homogamic matings are more frequent. Multifactorial analysis of variance shows that the number of matings are different for nine pairs of lines and four possible mating types (S_fS_m, S_fF_m, F_fS_m, F_fF_m). The rare male phenomenon is not dependent on different food composition, but is associated with variations in individual genotypes.     

Molecular basis of the optochin-sensitive phenotype of pneumococcus: characterization of the genes encoding the F0 complex of the Streptococcus pneumoniaeStreptococcus oralis H+-ATPases

The gene responsible for the optochin-sensitive (Opt^S) phenotype of Streptococcus pneumoniae has been characterized. Sequence comparisons indicated that the genes involved encoded the subunits of the F₀ complex of an H⁺-ATPase. Sequence analysis and transformation experiments showed that the atpC gene is responsible for the optochin-sensitive resistant (Opt^S/Opt^R) phenotype. Our results also show that natural as well as laboratory Opt^R isolates have arisen by point mutations that produce different amino acid changes at positions 48, 49 or 50 of the ATPase c subunit. The nucleotide sequence of the F F₀ complex of the Streptococcus oralis ATPase has also been determined. In addition, comparison of the sequence of the atpCAB genes of S. pneumoniae R6 (Opt^S) and M222 (an Opt^R strain produced by inter-species recombination between pneumococcus and S. oralis), and S. oralis revealed that, in M222, an interchange of atpC and atpA had occurred. We also demonstrate that optochin specifically inhibited the membrane-bound ATPase activity of the S. pneumoniae wild-type (Opt^S) strains, and found a 100-fold difference between Opt^S and Opt^R strains, both in growth inhibition and in membrane ATPase resistance.     

Newly characterized genetic polymorphism of uropepsinogen group A (PGA) using both isoelectric focusing and immunoblotting

Summary Genetic polymorphism of uropepsinogen group A (PGA) was characterized in human urine using a technique involving both polyacrylamide gel isoelectric focusing and immunoblotting with an anti-PGA antibody. PGA was clearly separable into five fractions, termed I to V in order of decreasing anodal mobility. The most slowly migrating fraction V was composed of F (fast) and/or S (slow) band(s). The population frequencies of the three patterns of fraction V (F, FS, and S) and family studies indicated that PGA V is controlled by a pair of alleles, PGA V ^* F and PGA V ^* S, at a single autosomal locus, and that both are codominant. The frequencies of the genes are 0.07 for PGA V ^* F and 0.93 for PGA V ^* S.     

Dominant and additive resistance to the root-knot nematodes Meloidogyne chitwoodi and M. fallax in Central American Solanum species

 The inheritance of resistance to Meloidogyne chitwoodi and M. fallax in Solanum fendleri, S. hougasii and S. stoloniferum was studied assuming disomic behaviour of these polyploid Solanum species. Various populations were produced from crosses within the wild Solanum species; resistant×susceptible and reciprocal crosses (F₁), self-pollinations (S₁), testcrosses (TC) and self-pollinations (F₂) of resistant hybrids, if possible. For the test crosses with S. hougasii, susceptible genotypes of S. iopetalum were used. In seedling tests, numbers of egg masses were counted after inoculation with M. chitwoodi or M. fallax. Almost all seedlings of the F₁ and S₁ populations of S. fendleri appeared to be resistant, whereas the TC and F₂ populations of three different resistant hybrid genotypes segregated into resistant (having 1 or no egg mass) and susceptible plants (having more than 1 egg mass) at ratios of 1:1 and 3:1, respectively. The results clearly indicate the action of a single dominantly inherited gene, and the symbol R _Mc2 is proposed for this gene. In the case of S. hougasii, F₁ and S₁ seedlings appeared to be mostly resistant. Difficulties were met in producing TC and F₂ populations, and only four TC populations were obtained, which segregated at a 1:1 ratio. These results also indicate the presence of a simple dominant factor. For both S. fendleri and S. hougasii no differences were observed between M. chitwoodi and M. fallax, indicating that resistance genes are the same for both nematode species. The F₁, S₁ and TC populations of S. stoloniferum segregated for the square root number of egg masses into normal-like distributions, which deviated between the Meloidogyne species used. The patterns indicate the presence of several additive genes and one or more genes effective to M. fallax but not to M. chitwoodi. The relationship of resistance genes present in various Central American Solanum species is discussed. Received: 24 September 1996/Accepted: 8 November 1996     

Selection against homozygotes in the ADH polymorphic system of Drosophila melanogaster associated with the lethal factor l(2) Stm

In the natural populations ⁺Tüb, ⁺Prov, and ⁺Rov, similar Adh ^F allele frequencies occur (q _F=0.11, 0.18, and 0.08, respectively). However, there is a discrepancy in that the Adh ^F allele in ⁺Tüb is closely linked to the lethal factor 1(2)Stm, which reduces relative fitness of the F phenotype to zero. In spite of this, polymorphism is maintained also in ⁺Tüb, because the heterozygotes are superior to the homozygous S type (relative fitness=0.88). Under laboratory culture conditions, in ⁺Tüb the relative fitness of the S genotype further decreases to 0.6. After outcrossing the lethal factor, relative fitnesses for S, FS, and F become 0.6, 1, and 0.48, respectively, implying that fitness for S remains the same. Relative values for S, FS, and F in ⁺Prov, not affected by the lethal factor, are calculated by the maximum average fitness method to be 1, 1.2, and 0.2 under the assumption that heterozygous FS are similarly superior to S as in the natural ⁺Tüb population and all allele frequencies found are stable equilibrium values.     

The distribution of Gc subtypes among the Mongoloid populations

The polymorphism of Gc (group-specific components) has been investigated for a series of 3,160 individual samples from 11 Mongoloid populations in Asia and North and South America by isoelectric focusing on polyacrylamide gels. The samples fall into six Gc phenotypes which can be explained by the three common alleles, Gc^1F, Gc^1S, and Gc², together with several variant phenotypes explained as the heterozygotes for the three common alleles. The distribution of Gc^1F suballele appears to be considerably different from population to population among Mongoloids, ranging from 0.105 (Machiguenga Indans, Peru) to 0.609 (Kadazan, Borneo). A clear geographic cline from Southeast Asia into South America in Gc^1F allele was observed in the populations. In general, Gc^1F allele frequencies are lower in European populations and higher in African populations. The range of variability in the Gc^1F values observed among the Asiatic populations is between the Africans and the Europeans.     

Hemoglobins, haptoglobins, and transferrins in indigenous populations of Kenya

Hemoglobin, haptoglobin, and transferrin phenotypes were determined by means of starch-gel electrophoresis for a sample of 226 Kenya hospital patients. Allele frequencies were: Hb_β^S=0.081; Hp¹=0.057; Tf^D=0.038. Hemoglobin S was the only aberrant hemoglobin found in this sample. Transferrins C and D were the only transferrins found. Hemoglobin and transferrin phenotypes were also determined for a sample of 201 newborn Kenya infants. One of these infants had hemoglobins F, S, and C, eight had hemoglobins A, F, and S, and the remainder had hemoglobins A and F. Transferrins C, B, and D were found in this sample. Allele frequencies were: Tf^B=0.008; Tf^D=0.019.     

Linkage of C4 and C4 deficiency to BF and GPLA

The C4, Bf, and GPLA phenotypes of homo- and heterozygous C4-deficient guinea pigs were studied. The electrophoretic patterns suggest that the deficiency in circulating C4 results from an impaired structural gene, allelic to the C4^F, C4^S, and C4^S1 alleles at the C4 locus. In family studies, support for linkage of C4 and Bf to theGPLA system was obtained. The defective gene appears to be the fourth allele, which is rare, in the polymorphism of the fourth component of guinea pig complement.Abbreviations used in this paper are as follows Bf locus for properdin factor B - MHC major histocompatibility complex - GPLA major histocompatibility complex of the guinea pig     

Epigenetics of dominance for enzyme activity

We have isolated and purified two parental homodimers and a unique heterodimer of acid phosphatase [coded byAcph-1 ^1.05(F) andAcph-1 ^0.95(S)] from isogenic homozygotes and heterozygotes ofDrosophila malerkotliana. F andS produce qualitatively different allozymes and the two alleles are expressed equally within and across all three genotypes andF andS play an equal role in the epigenetics of dominance. Subunit interaction in the heterodimer over a wide range of H⁺ concentrations accounts for the epigenetics of dominance for enzyme activity     

Genetic regulation of liver alcohol dehydrogenase in Peromyscus

Data from genetic crosses of Peromyscus maniculatus and P. polionotus suggest that electrophoretic variants of liver alcohol dehydrogenase are coded by alleles at a single locus. These alleles, designated Adh ^F , Adh ^S , and Adh ^N , determine, respectively, the fast, slow, and not detectable (null) ADH electrophoretic phenotypes. Heterozygotes (Adh ^F /Adh ^S ) exhibit three bands on zymograms, suggesting a dimeric subunit structure for the enzyme. However, Adh ^F /Adh ^N and Adh ^S /Adh ^N animals exhibit a single band, suggesting that the Adh ^N allele does not produce a polypeptide subunit capable of dimerizing into an active molecule. Fast and slow electrophoretic phenotypes exhibit multiple bands which can be converted into single major fast and slow bands, respectively, upon treatment with oxidized or reduced NAD. Addition of NAD also stabilizes both the fast and slow enzyme to heat inactivation at 60 C for at least 30 min.This work was supported by Predoctoral Fellowship AA-05067 from the National Institute of Alcohol Abuse and Alcoholism to K. G. B. and South Carolina Commission on Alcohol and Drug Abuse Grant 7607. Also, partial support was provided by NIH Grant CA-16184.     

Dominance Relationship between Two Self-Incompatible<Emphasis Type="Italic">Brassica campestris</Emphasis> Haplotypes in Response to CO<Subscript>2</Subscript> Gas

InBrassica, self-incompatibility (SI) can be overcome by CO₂ application, an effective method for obtaining numerous inbred lines for F, commercial seed. We previously reported two different S-alleles ofBrassica campestris, S⁷³³ and S⁷³⁴, with extremely different degrees of susceptibility to this gas. In the current study, we raised a cross-population between those two genetic lines, and analyzed their reaction level of self-incompatibility to CO₂ (RLSICO₂). Here, all 40 of our progeny from the F₁ cross-population were susceptible, maintaining high values of RLSICO₂. This suggests that the susceptible line, S⁷³⁴, is dominant to the insusceptible line, S⁷³³. We also generated an F₂ selfing-population of each crossed progeny, S⁷³³♀ S⁷³⁴♂ and S⁷³³♂ S⁷³⁴♀, to assess the RLSICO₂ of each individual. PCR-RFLP analysis was performed to determine the S-genotype of the F₂ population. The S⁷³⁴ allele segregated in a theoretical ratio of the dominant trait, and the RLSICO₂ was consistent with the dominance relationship. Therefore, we have now demonstrated that high RLSICO₂ in β.campestris is controlled by a dominant gene. Both authors contributed equally to this work     

Partial monosomy 22 as the result of an unbalanced translocation 5:22 in a patient with cri-du-chat syndrome

Summary Properdin factor B phenotypes were determined in 7 Bantu speaking Negroid populations, 1 Indian, and 1 Colored population of South Africa in a total of 1258 individuals. In the Negroid populations allele frequencies were: Bf^F 0.655, Bf^S 0.282, Bf^RARE 0.063, in the Indian population: Bf^F 0.322, Bf^S 0.645, Bf^RARE 0.033, and in the Colored population: Bf^F 0.513, Bf^S 0.435, Bf^RARE 0.052. In addition, 2 so far unknown F alleles and possibly 1 new S allele were discovered.     

Genes required for both gliding motility and development in Myxococcus xanthus

Myxococous xanthus cells can glide both as individual cells, dependent on A dventurous motility (A motility), and as groups of cells, dependent upon S ocial motility (S motility), Tn5-lac mutagenesis was used to generate 16 new A^- and nine new S^- mutations. In contrast with previous results, we find that subsets of A^- mutants are defective in fruiting body morphogenesis and/or myxospore differentiation. All S^- mutants are defective in fruiting body morphogenesis, consistent with previous results. Whereas some S^- mutants produce a wild-type complement of spores, others are defective in the differentiation of myxospores. Therefore, a subset of the A genes and all of the S genes are critical for fruiting body morphogenesis. Subsets of both A and S genes are essential for sporulation. Three S::Tn5–lac insertions result in surprising phenotypes. Colonies of two S^- mutants glide on ‘swim’ (0.35% agar) plates to form fractal patterns. These S^- mutants are the first examples of a bacterium in which mutations result in fractal patterns of colonial spreading. An otherwise wild-type strain with one S^- insertion resembles the frz^- sglA1^- mutants upon development, suggesting that this S^- gene defines a new chemotaxis component in M. xanthus.     

Genetics of complement C4. Two homoduplication haplotypes C4S C4S and C4F C4F in a family

Summary A family in which two homoduplicated C4 haplotypes (or supergenes) segregate is described. One haplotype C4F ^* 3 C4F ^*2.2 is composed of two C4F alleles and the other C4S ^* 5.1 C4S ^*1 of two C4S alleles. The C4F duplication haplotype is a partial inhibitor of the Rodgers antigen, and judged from our family and population material, it seems to be rather frequent and associated with HLAB ^*35, Bf ^* F, and HLAD/DR ^*1. The C4S duplication haplotype is Rg(a-) and is not identified in individuals without another S, Ch(a+) variant.This work was supported by grant No 12-1727 from the Danish Medical Research Council     

Physiological effects of an allozyme polymorphism: Glutamate-pyruvate transaminase and response to hyperosmotic stress in the copepod Tigriopus californicus

In order to regulate cell volume during hyperosmotic stress, the intertidal copepod Tigriopus californicus, like other aquatic crustaceans, rapidly accumulates high levels of intracellular alanine, proline, and glycine. Glutamate-pyruvate transaminase (GPT; EC 2.6.1.2), which catalyzes the final step of alanine synthesis, is genetically polymorphic in T. californicus populations at Santa Cruz, California. Spectrophotometric studies of homogenates derived from a homozygous isofemale line of each of the two common GPT alleles indicated that the GPT^F allozyme has a significantly higher specific activity than the GPT^S allozyme. Under conditions of hyperosmotic stress, individual adult copepods of GPT^F and GPT^F/S genotypes accumulated alanine, but not glycine or proline, more rapidly than GPT^S homozygotes. When young larvae were subjected to the same hyperosmotic conditions, GPT^S larvae suffered a significantly higher mortality than GPT^F or GPT^F/S larvae. These results suggest that the biochemical differences among GPT allozymes result in specific physiological variation among GPT genotypes and that this physiological variation is manifested in differential genotypic survivorships under some naturally occurring environmental conditions.This work was supported in part by a grant from the Lerner Fund for Marine Research of the American Museum of Natural History, an NIH Training Grant in Integrative Biology, and NIH Grants GM 28016 and GM 10452.     

Sex-limited genetic variation in a mouse salivary protein

This report describes a gene which influences the electrophoretic mobility of a protein in the salivas of adult mice. Three categories of phenotype have been observed: the two single-banded types, F (Fast) and S (Slow), and the two-banded type, SF (Slow-Fast), with the two bands represented in varying proportions. All females, regardless of age or strain, and all males before puberty show only the F phenotype. Males of the BALB/c and C57BL/6J strains show the F phenotype throughout puberty and adult life, whereas males of the C3H/St and C57BL/KsJ strains show the SF phenotype in puberty and the S phenotype in adult life. We have designated this variation the sex-limited saliva pattern (Ssp). The results from genetic crosses indicate that the variation among the strains is determined by an autosomal locus, Ssp, with two alleles, Ssp ^S andSsp ^F ,where Ssp ^S is dominant to Ssp ^F .Testosterone treatment can accelerate the acquisition of the S type in males of the strains C3H/St and C57BL/KsJ and also induces that phenotype in C3H/St females and C57BL/6J males. Thus it appears that the observed strain-specific differences reflect a genetic variation in androgen levels and/or androgen sensitivity rather than variation in a structural gene.This study was supported in part by PHS Research Grant 5 RO1 AM21177 and by the Indiana University Human Genetics Center (PHS PO1 GM21054). The preliminary work was done during a 1-month visit by RCK to the Institute of Ecology and Genetics which was supported by the University of Aarhus. This is publication No. 80-18 from the Department of Medical Genetics. RCK was supported by PHS Career Development Award 1 KO4 AM00284. SRD was supported by PHS General Medical Training Grant T32 GM07468.     

Molecular studies of FIme resistance plasmids, particularly in epidemic Salmonella typhimurium.

Summary The molecular sizes of F₁ me resistance plasmids from strains of Salmonella typhimurium, S. wien and S. typhi were within the range 87.9–102.6×10⁶ daltons. DNA reassociation studies indicated that the plasmids from these hosts had at least 80% of their nucleotide sequences in common. A high proportion of F₁ me plasmids cannot mediate their own transfer. The non-autotransferring property of such plasmids is the result of DNA deletion; a non-autotransferring F₁ me plasmid was about 10×10⁶ daltons shorter than autotransferring representatives of the group, and its DNA showed 100% homology with them. Plasmids of the F₁ me group are incompatible with the F factor and with F₁R factors. F₁ me plasmids are incompatible with the fi ⁺ MP10 plasmid of S. typhimurium, whereas F and F₁ factors are compatible with MP10 (Anderson et al., 1977). There was no significant DNA homology between members of the F₁ me group and MP10, and these plasmids may share only a small region of DNA responsible for their incompatibility. The F₁ me R factors examined had 29–37% DNA homology with the F factor, and 50–58% homology with the F₁ resistance plasmid, R162. Molecular examination therefore supports the genetic differentiation of members of the F₁ me group from other F-like plasmids. Both types of investigation can thus be used in epidemiological studies of bacterial strains carrying resistance or other plasmids.     

The genetic control of grain esterases in hexaploid wheat

Summary A comparison of EST-5 grain esterase phenotypes from wheat-alien amphiploid, addition and substitution genotypes, resolved by flat-bed isoelectric focusing identified homoeologous Est-5 loci on chromosome 3H of Hordeum vulgare, 3H^ch of H. chilense, 3S^b of Aegilops bicornis, 3S¹ of Ae. sharonensis and Ae. longissima and 6R of Secale cereale and 6R^m of S. montanum. The Est-5 genes in alien species provide evidence for chromosome homoeology with wheat.     

Point mutagenesis in mouse reveals contrasting pathogenetic effects between MEN2B- and Hirschsprung disease-associated missense mutations of the RET gene

Missense mutations of the RET gene have been identified in both multiple endocrine neoplasia (MEN) type 2A/B and Hirschsprung disease (HSCR: congenital absence of the enteric nervous system, ENS). Current consensus holds that MEN2A/B and HSCR are caused by activating and inactivating RET mutations, respectively. However, the biological significance of RET missense mutations in vivo has not been fully elucidated. In the present study, we introduced one MEN2B-associated (M918T) and two HSCR-associated (N394K and Y791F) RET missense mutations into the corresponding regions of the mouse Ret gene by genome editing (Ret^M919T, Ret^N396K and Ret^Y792F) and performed histological examinations of Ret-expressing tissues to understand the pathogenetic impact of each mutant in vivo. Ret^M919T/+ mice displayed MEN2B-related phenotypes, including C-cell hyperplasia and abnormal enlargement of the primary sympathetic ganglia. Similar sympathetic phenotype was observed in Ret^M919T/- mice, demonstrating a strong pathogenetic effect of the Ret M918T by a single-allele expression. In contrast, no abnormality was found in the ENS of mice harboring the Ret N394K or Y791F mutation. Most surprisingly, single-allele expression of RET N394K or Y791F was sufficient for normal ENS development, indicating that these RET mutants exert largely physiological function in vivo. This study reveals contrasting pathogenetic effects between MEN2B- and HSCR-associated RET missense mutations, and suggests that some of HSCR-associated RET missense mutations are by themselves neither inactivating nor pathogenetic and require involvement of other gene mutations for disease expressivity.