Showing papers in "Genetics Research in 1982"

Selection against harmful mutations in large sexual and asexual populations.

Abstract: Selection against harmful mutations in large populations is studied assuming that the rate of fitness decrease grows with every new mutation added to a genome. Under this reasonable assumption (Mayr, 1970) the average fitness of a sexual population, without linkage between the loci, is higher, and the average equilibrium number of harmful mutations per individual lower, than in an asexual population. If a gamete contains on the average one or more new mutations, the resulting advantage of sexual reproduction and recombination seems to be sufficient to counterbalance the double advantage of parthenogenesis. Moreover, selection against harmful mutations is probably the most powerful factor preventing linkage disequilibrium even with epistatic interaction between the loci.

Predictions of response to artificial selection from new mutations.

Abstract: The pattern of response expected from fixation of mutant genes for quantitative traits in finite populations is investigated for a range of distributions of mutant gene effects. The eventual rate depends on the total variance of mutant effects per generation, but the initial rate and the variance of response is higher if the distribution of mutant effects has a large standard deviation or is leptokurtic. The difference between initial and eventual rates of response is greater with large population sizes.For a range of assumptions, new mutants are unlikely to have much influence on response for 20 or so generations, but then may contribute substantially, such that no plateaux are obtained. However, information on the variance contributed by mutants is almost entirely on bristle number in Drosophila.It is argued that the role of new mutants should be considered in designing breeding programmes, in particular in utilizing large populations.

Genetic differentiation of quantitative characters between populations or species: I. Mutation and random genetic drift

Abstract: Introducing a new genetic model called the discrete allelic-state model, the evolutionary change of genetic variation of quantitative characters within and between populations is studied under the assumption of no selection. This model allows us to study the effects of mutation and random genetic drift in detail. It is shown that when the allelic effects on phenotype are additive, the rate of approach of the genetic variance within populations to the equilibrium value depends only on the effective population size. It is also shown that the distribution of genotypic value often deviates from normality particularly when the effective population size and the number of loci concerned are small. On the other hand, the interpopulational variance increases linearly with time, if the intrapopu-lational variance remains constant. Therefore, the ratio of interpopulational variance to intrapopulational variance can be used for testing the hypothesis of neutral evolution of quantitative characters.

A new allele sash (Wsh) at the W-locus and a spontaneous recessive lethal in mice.

Abstract: A mutation to an apparently new allele at the W-locus of the mouse arose spontaneously in a cross between two inbred strains. Heterozygotes have a broad white sash, leading to the name and symbol sash, Wsh. Homozygotes are black-eyed whites which are viable, fertile and not anaemic, although the gene does cause mild haematopoietic defects. The original mutant animal also carried a spontaneous recessive lethal mutation on chromosome 5, mapping at 2 cM distal to the W-locus.

Estimation and interpretation of genetic distance in empirical studies.

Abstract: Linear functions of Nei's genetic-distance statistic are calculated frequently in the literature of population genetics. Variance estimates for these linear functions are either not presented or incorrectly calculated. Part of the problem stems from the common assumption that distance statistics are independent random variables. This assumption is not generally correct. We describe methods for estimating the variance of linear combinations of genetic-distance statistics. We also suggest a method for constructing confidence intervals on genetic-distance statistics when these values are small (< 0·10) and their distribution deviates substantially from normal.

Genetic basis and natural variation of α-amylase isozymes in barley

Abstract: Two physiologically and biochemically distinct groups of α-amylase (E.C.3.2.1.1) isozymes are synthesized when isolated aleurone layers of barley are incubated with gibberellic acid (GA3). Isoelectric focusing of the α-amylases showed that the isoelectric points of the isozymes of one group were near pH 5, whereas those of the second group were close to pH 6. Using wheat–barley addition lines, the genes for these groups were located in barley chromosomes 1 and 6 respectively. Joint segregation in the F2 generation of appropriate crosses indicated that the isozymes within each group were inherited collectively, and were attributed to codominant alleles segregating at two presumably complex loci, α-Amy 2 and α-Amy 1.The extent of genetic variation at these two loci was examined in 40 lines of Hordeum spontaneum (the wild progenitor of barley), and in a complex gene pool representative of H. vulgare (composite cross XXI). Variation at the α-Amy 1 locus was much more extensive than that at the α-Amy 2 locus. The genetic variation at both α-amylase loci exceeded that at the majority of other allozyme loci. However the α-amylase loci were less variable than the two loci coding for the seed storage protein, hordein. The wild species was found to contain much genetic diversity, which might be useful in modifying α-amylase activity by breeding. Parallels between the genetics and variation of α-amylase in barley and wheat were noted.

Sex-determinants and their distribution in various populations of Musca domestica L. of Western Europe

Abstract: The distribution of sex-determinants in field populations of Musca domestica domestica L. was studied in 62 samples of flies collected at 53 sites (animal farms) between 1975 and 1981 in an area stretching North–South from Denmark (+ Iceland) to Sicily.Karyological observations and genetic analyses demonstrated the existence of three types of population along a latitudinal cline. Populations of Northern Europe were of the standard type (XX females and XY males) with the Y chromosome determining sex. Those of Central and Southern Italy from sites below 100 m.a.s.l. (metres above sea level) were autosomal (XX females and males), sex in them being determined by autosomal sex-determinants for both femaleness and maleness. In the large intermediate zone the populations were mixed and had several karyotypes in both sexes. In this zone an altitudinal gradient was also observed, with autosomal determinants less common at higher altitudes. Genetic tests showed, in the autosomal and in the mixed populations, the presence of two autosomal male factors: M III, the most common, on autosome III and M II, on autosome II.The gradient in sex determinants found in flies of Western Europe appears to be a dynamic phenomenon of relatively recent origin. Both climatic influence and selective pressure with insecticides have probably contributed towards the micro-evolution of populations with different sex-determinants in the houseflies of the area studied.

Models of mitochondrial DNA transmission genetics and evolution in higher eucaryotes

Abstract: The future value of mitochondrial DNA (mtDNA) sequence information to studies in population biology will depend in part on understanding of mtDNA transmission genetics both within cell lineages and between animal generations. A series of stochastic models has been constructed here based on various possibilities concerning this transmission. Several of the models generate predictions inconsistent with available data and, hence, their assumptions are provisionally rejected. Other models cannot yet be falsified. These latter models include assumptions that (1) mtDNA's are sorted through cellular lineages by random allocation to daughter cells in germ cell lineages; (2) the effective intracellular population sizes (nM's) of mtDNA's are small; and (3) sperm may (or may not) provide a low level ‘gene-flow’ bridge between otherwise isolated female lineages. It is hoped that the models have helped to identify and will stimulate further empirical study of various parameters likely to strongly influence mtDNA evolution. In particular, critical experiments or measurements are needed to determine the effective sizes of mtDNA populations in germ (and somatic) cells and to examine possible paternal contributions to zygote mtDNA composition.

Path analysis under generalized assortative mating. II. American I.Q.

Abstract: Rice, Cloninger & Reich (1980) showed that correlational data on American I.Q. is consistent with a rather low genetic heritability. Here we confirm their general results with a more parsimonious model. From phenotypic data alone, the estimates of genetic and cultural heritability are 0·31 and 0·42, respectively. Using environmental indices, the parsimonious estimates become 0·34 and 0·26, respectively.

Nucleotide sequences of highly repeated DNAs; compilation and comments.

Abstract: The nucleotide sequence data from highly repeated DNAs of inverte-brates and mammals are summarized and briefly discussed. Very similar conclusions can be drawn from the two data bases. Sequence complexities can vary from 2 bp to at least 359 bp in invertebrates and from 3 bp to at least 2350 bp in mammals. The larger sequences may or may not exhibit a substructure. Significant sequence variation occurs for any given repeated array within a species, but the sources of this heterogeneity have not been systematically partitioned. The types of alterations in a basic repeating unit can involve base changes as well as deletions or additions which can vary from 1 bp to at least 98 bp in length. These changes indicate that sequence per se is unlikely to be under significant biological constraints and may sensibly be examined by analogy to Kimura's neutral theory for allelic variation. It is not possible with the present evidence to discriminate between the roles of neutral and selective mechanisms in the evolution of highly repeated DNA.Tandemly repeated arrays are constantly subjected to cycles of amplification and deletion by mechanisms for which the available data stem largely from ribosomal genes. It is a matter of conjecture whether the solutions to the mechanistic puzzles involved in amplification or rapid redeployment of satellite sequences throughout a genome will necessarily give any insight into biological functions.The lack of significant somatic effects when the satellite DNA content of a genome is significantly perturbed indicates that the hunt for specific functions at the cellular level is unlikely to prove profitable.The presence or in some cases the amount of satellite DNA on a chromosome, however, can have significant effects in the germ line. There the data show that localized condensed chromatin, rich in satellite DNA, can have the effect of rendering adjacent euchromatic regions rec−, or of altering levels of recombination on different chromosomes. No data stemming from natural populations however are yet available to tell us if these effects are of adaptive or evolutionary significance.

Mutants affecting amino acid cross-pathway control in Neurospora crassa.

Abstract: Arginine-requiring mutants of Neurospora crassa were isolated using a strain partially impaired in an enzyme of the arginine pathway (bradytroph). Among these, five strains were found which carry mutations at a new locus, cpc-l. The recessive cpc-1 alleles interfere with the crosspathway control of amino acid biosynthetic enzymes. The enzymes studied, three of arginine and one each of histidine and lysine biosynthesis, fail to derepress under conditions which normally result in elevation of enzyme concentration, namely arginine, histidine or tryptophan limitation. Enzymes not involved in amino acid biosynthesis are still able to derepress in the presence of cpc-1. In wild-type backgound, i.e. with the bradytroph replaced, cpc-1 strains lose the original arginine-requirement. cpc-1 mutations confer sensitivity of growth to 3-amino-l,2,4-triazole.

Primary non-random X-inactivation caused by controlling elements in the mouse demonstrated at the cellular level.

Abstract: Previous studies have shown that different alleles of the mouse X chromosomal controlling element locus, Xce, cause non-random X-chromosome inactivation as judged by variegation in the coats of female mice heterozygous for X-linked coat colour/structure genes, or Cattanach's translocation (Is (X; 7) Ct), or the relative activity of biochemical variants of the X-linked enzyme PGK This paper presents evidence using the Kanda differential staining method on 6½ dpc and 13½ dpc female mouse embryos heterozygous for the marker X chromosome Is (X; 7) Ct and carrying different Xce alleles, that the Xce locus affects the randomness of X chromosome inactivation Furthermore the fact that a marked Xce effect is demonstrable in female embryos as early as 6½ dpc (ie very soon after the initial time of X-inactivation) is strong evidence that the Xce locus exerts its effect by causing primary non-random X-inactivation rather than by cell selection after initial random X-inactivation

The cytogenetic boundaries of the rDNA region within heterochromatin in the X chromosome of Drosophila melanogaster and their relation to male meiotic pairing sites.

Abstract: The proximal breakpoints of the inversion chromosomes In ( 1 )ω m 4 and In ( 1 ) m 51 b were shown, by in situ hybridization, to define the boundaries of the ribosomal DNA region located within the X chromosome heterochromatin ( Xh ). We estimate that at least 95% of the rDNA is located between the In ( 1 )ω m 4 and In ( 1 )ω m 51 b proximal breakpoints. In contrast only 60–70% of the Type I intervening sequences located in Xh are located between these breakpoints. The Type I intervening sequences in the rDNA region occur as inserts in the 28S rRNA sequences while the remainder of the sequences are distal to the In ( 1 )ω m 4 breakpoint and not associated with rRNA genes. The regions of Xh which contain rDNA and Type I intervening sequences were related to regions shown by Cooper (1964) to contribute to meiotic pairing between the X and Y chromosomes in male Drosophila. We demonstrate that the rRNA coding region contributes to X / Y pairing. However, no single region of Xh is required for fidelity of male meiotic pairing of the sex chromosomes.

The extent to which gene conversion can change allele frequencies in populations

Abstract: The gene conversion parameters which affect allele frequencies in populations are defined, and their ranges and typical values are given for several genera of fungi, where meiotic octads and tetrads provide the best information on conversion. Both gene conversion and disparity in direction of conversion are common. Data from Ascobolus immersus show that conversion properties are largely stable with time, but can be changed environmentally and by genetic conversion control factors. Equations are given for the interactions of selection, mutation and gene conversion in determining equilibrium frequencies. Numerical examples, using typical values of conversion parameters from the fungal data, show that for alleles which are selectively neutral or have very low selection coefficients, conversion will often have very large effects on their equilibrium frequencies and may lead to fixation. Where selection coefficients are higher, conversion has major effects on the frequencies of deleterious recessive alleles, but lesser effects on deleterious dominant alleles: a critical comparison is that of s with 2y. The available estimates for conversion parameters (at least in fungi) are of a magnitude to make gene conversion an important factor in evolution.

Temperature-sensitive paralytic mutations on the second and third chromosomes of Drosophila melanogaster

Abstract: Seven temperature-sensitive paralytic mutants were recovered from 4544 lines of ethylmethanesulphonate (EMS) treated autosomes in Drosophila melanogaster. These mutants have been designated temperature-induced paralytic (tip). The tip mutations belong to six different genes; four of these, tip-A, Tip-B, tip-C and tip-D are on the second chromosome while tip-E and tip-F are on the third chromosome. This paper describes the paralysing behaviour and genetic localization of the tip mutants.

The relationship between heterochromatic homology and meiotic segregation of compound second autosomes during spermatogenesis in Drosophila melanogaster

Abstract: In this report we examine the meiotic segregation of compound second autosomes sharing varying extents of heterochromatic and euchromatic homology. The second chromosome heterochromatin does not appear to influence the random meiotic segregation of compound second autosomes during spermatogenesis; however, the proximal euchromatin is implicated in male meiotic pairing. We conclude that male autosomal meiotic pairing sites are specific euchromatic chromosomal regions.

A computer model of speciation by founder effects

Abstract: A computer model of a two-locus genetic system with epistatic selection was used to investigate factors influencing the probability of the origin of reproductive isolation, due to a genetic revolution following a founder event (Mayr, 1954; Carson, 1975). Restricted population size can sometimes cause such a system to drift from one equilibrium to another, which can result in loss of fitness to hybrids with the ancestral population. The chance of such an event was found to be low unless the bottleneck in population size associated with the founder event was preceded by many generations of relaxed selection. It is highest when the bottleneck is not prolonged and when the population size during the bottleneck is not too small. It seems to be difficult to achieve a high degree of reproductive isolation in one step by this method, and it is concluded that it is unlikely to be a major cause of rapid speciation, although it could be a contributory factor.

Increased sensitivity to cell killing and mutagenesis by chemical mutagens in thymidine-kinase-deficient subclones of a Friend murine leukaemia cell line.

Abstract: Wild-type Friend murine leukaemia (clone 707) cells and two thymidinekinase-deficient subclones, 707BUE and 707BUF, were compared for sensitivity to killing and mutagenesis by the chemical mutagens, ethyl methane sulphonate (EMS), N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), mitomycin C (MMC), and methyl methane sulphonate (MMS). The two thymidine-kinase-deficient subclones were significantly more sensitive to killing by each of the four chemical mutagens than were wild-type cells. The increased sensitivity to killing by the four mutagens was also reflected in increased mutagenesis (per unit dose of mutagen) to 6-thioguanine resistance. In the light of these results, the significance of thymidine kinase in DNA repair and mutagenesis is discussed.

The orientation of transfer of the plasmid RP4

Abstract: The probably identical broad host range plasmids RP4, RP1 and RK2 (Datta et al. 1971; Grinsted et al. 1972; Olsen & Shipley, 1973; Meyer et al. 1975; Beringer, 1974; Towner & Vivian, 1976) have been extensively studied as vectors for in vitro recombi nation and mediators of conjugative transfer of DNA between species (Olsen & Gonzalez, 1974; Jacob et al. 1976; Dixon et al. 1976; Stepanov et al. 1976; Meyer et al. 1977; Nagahari et al. 1977). Studies of the conjugation system have led to the identification of transfer (tra) genes and have mapped the drug resistance determinants (Barth & Grinter, 1977; Grinsted et al. 1977; Thomas et al. 1979). We present here a deletion analysis which shows in which direction the plasmid is transferred during conjugation. A short (5-7 kb) A fragment (Szybalski & Szybalski, 1979; Daniels et al. 1980) containing att and int was inserted into the single EcoRI site of RP4 (Jacob & Grinter, 1975; Pastrana, 1976; Pastrana & Brammar, 1979). The recombinant plasmid can integrate into att\ on the Escherichia coli chromosome to form a stable Hfr strain (Watson & Scaife, 1978). It transfers the chromosome in the orientation: O-lac-leu-thr.. .trp. We have recently reported (Watson & Scaife, 1980) that plasmid excision specifically depends on the xis function of A, confirming that Hfr formation is mediated by irci-directed, site-specific recombination and, by implication, uses att in the same orientation as the parent phage. Chromosome transfer by the Hfr thus allows us to establish the orientation of the Aatt fragment relative to the chromosome. Here, we present deletion studies with an RP4 Aatt derivative, pZDIOO (Al-Doori and Scaife, in preparation) which establish the orientation of the phage fragment in the original plasmid. The plasmid pZDIOO carries Arfn/18 inserted at att (Fig. 16). This phage makes a dominant rifampicin-resistant (rif°) RNA polymerase /? subunit (Kirschbaum & Konrad, 1973) and a temperature-sensitive phage repressor (c!857) (Sussman & Jacob, 1962). Electron microscope studies on pZDIOO DNA (date not shown) indicate that it occurs in several non-multimeric sizes. For this reason we have preferred to analyse deletion mutants of pZDIOO which exist in a single form and were made as follows. Bacteria carrying pZDIOO cannot form colonies on rifampicin medium at 42 °C since the phage is induced and is either excised from the plasmid or interferes with its replication. However, rare mutants do grow on this medium. They have deletions extending through most of the prophage into the plasmid DNA (Fig. 1). Two such deletion plasmids, pZD23 and pZD44 have been analysed in detail (Plate la and b).

Close linkage between albumin and vitamin D binding protein (gc) loci in chicken: a 300 million year old linkage group.

Abstract: Evidence for close genetic linkage between the structural loci for serum albumin ( Alb ) and serum vitamin D binding protein ( Gc ) in chicken is presented. The results are based on a study of a single sire family comprising 36 informative offspring. No recombinants have been observed. It is concluded that this linkage in the chicken is homologous to the close linkage of the albumin and Gc loci reported in man and the horse. Thus, this linkage group has most probably been conserved for at least 300 million years.

Allelic variation at several different genetic loci determines the major urinary protein phenotype of inbred mouse strains.

Abstract: We have examined the major urinary protein (MUP) phenotype of three inbred mouse strains by one-dimensional isoelectric focusing in acrylamide gels. Each strain gave a distinct pattern of major and minor bands. In the three strains together, seven major and about seven minor bands were observed. F1 phenotypes were intermediate. F2 phenotypes can be explained by recombination between allelic variants at four or more different genetic loci. We propose that variation in MUP phenotype is due in fact, to allelic variation at approximately seven structural gene loci, some of which are linked on chromosome 4. The remainder may or may not be linked to these.

Genetic background affects expression of t haplotype in mouse sperm.

Abstract: Two aspects of sperm phenotype were examined for t w 32 /+ males of the inbred strains C3H and C57BL/6 (B6). Sperm from fertile C3H- t w 32 /+ males very rarely achieved fertilization in vitro, while sperm from congenie C3H-+/+ males had no such difficulties. The presence of t w 32 had no effect on ability of B6 sperm to undergo fertilization in vitro. In fertile hybrid males produced from crosses of B6 and C3H strains, t w 32 significantly reduced, but did not inhibit completely, the sperms' ability to fertilize in vitro. The presence of t w 32 decreased by a factor of two the frequency of abnormal sperm heads in males of the B6 strain, but doubled the frequency in the C3H strain. Hybrid males resembled the C3H strain in this respect. The presence of T or T 2 J had no effect on the level of sperm abnormalities in any strain. These results emphasize the importance of genetic background in expression of t haplotypes in sperm, and suggest that t w 32 can influence a range of sperm characteristics, by interacting with products of other loci.

Multiple allelism at the locus controlling warfarin resistance in the Norway rat.

Abstract: Two warfarin-resistant strains of the Norway rat, Rattus norvegicus, derived independently from wild populations in Wales and Scotland and both homozygous for a major gene at the warfarin-resistance locus, Rw, were found to differ in their hypoprothrombinaemic response to simultaneous dosage with warfarin and vitamin K. The Welsh strain gave a small response and the Scottish strain a large response. These two response levels segregated in Mendelian fashion in various crosses involving the two resistant strains and a third, non-resistant strain. This indicates that the Rw locus has a series of three multiple alleles, denoted Rww, Rws and Rw+. The results are discussed briefly in relation to biochemical, ecological and evolutionary aspects of warfarin resistance.

The structure of hair and follicles of mice carrying the naked (N) gene.

Abstract: The hairs and follicles from mice carrying the naked ( N ) gene have been examined using both scanning and transmission electron microscopy in addition to light microscopy. Fibre cuticle cells and occasionally cortical cells were absent from the follicles of N / + mice when the base of the hair was growing. In N / N follicles there was a frequent lack of both cuticle and cortical cells throughout the growth phase of the follicles. Abnormalities were also observed in the manner in which the synthesized keratin was deposited in the fibres. The possible mode of action of the N gene is discussed in the light of these results.

Competitive mating in Drosophila melanogaster

Abstract: Selective differences among male Drosophila melanogaster due to differences in ability to compete for mates may often have been under-estimated in the past because, under the test procedure used, females did not represent a limited resource. In the experiment reported here, no difference was detected between inbred and outbred males ‘competing’ to mate with an equal number of females. When the receptive female: male ratio was halved a large reduction in male mating ability due to inbreeding became apparent.

Studies of esterase 6 in Drosophila melanogaster: XI. Modification of esterase 6 activity by unlinked genes

Abstract: The often remarkable similarity in structural gene products among related species has led to the hypothesis that species differences may reside largely in changes at regulatory gene loci. This hypothesis assumes that groups capable of speciating have allelic variation at regulatory loci in their natural populations. We have undertaken an analysis of the mode of regulation of the esterase 6 (Est 6) locus in Drosophila melanogaster to determine the nature and extent of regulatory gene variation in natural populations. Analyses of esterase 6 (EST 6) activity among strains carrying the same thermostability variants reveal that significant, specific-activity differences are present. Reciprocal crosses between lines having high and low EST 6 activity show that loci other than the Est 6 structural gene influence EST 6 activity. Analyses of male hybrids from crosses between D. melanogaster and simulans indicate that the X chromosome of these flies affects the expression of the Est 6 locus, resulting in unequal levels of enzyme activity from the two alleles. The effect is sex and tissue specific. Female hybrids carrying the X chromosomes of both species exhibit equal expression of the two Est 6 alleles. We have determined whether natural populations are polymorphic for X chromosomes which affect EST 6 activity by extracting single X chromosomes from wild-collected males and placing these chromosomes in identical genetic backgrounds. Stocks which are otherwise genetically identical but carry independently derived X chromosomes show significant differences in the activity of EST 6. These data suggest that regulatory loci may be commonly polymorphic in natural populations.

Linkage disequilibrium, genetic distance and evolutionary distance under a general model of linked genes or a part of the genome

Abstract: A general model of linked genes or a part of a genome is proposed which enables us to study various problems in molecular population genetics in a unified way. Several formulae with special reference to the linkage disequilibrium and genetic distance are derived for neutral mutations in finite populations, based on the method of diffusion equations. It is argued that the model and formulae are useful particularly when observations are made in terms of DNA sequence.