Autosomal recessive lethal mutations in two mutator stocks of Drosophila ananassae.

The frequency of recessive lethals in the 2nd chromosome was examined in two mutator stocks of Drosophila ananassae, ca and ca; px. They are characterized respectively by possessing an extrachromosomal clastogenic mutator in males, and by the retrotransposon "tom", which induces Om mutability only in females. The frequencies of recessive lethal mutations in the 2nd chromosome among progenies from males and females of the ca; px stock are 0.35 and 0.34 percent, respectively. Similarity of these frequencies indicates that tom does not induce recessive lethals in females. In contrast to the ca; px stock, the frequency of recessive lethals in males of the ca mutator stock was estimated to be 1.54 percent for the 2nd chromosome. No visible mutants except Minutes were recovered. Some recessive lethals derived from ca stock males were associated with chromosomal rearrangements. Being consistent with its high rate of Minute mutation it was demonstrated that the ca clastogenic mutator also induced recessive lethals.     

A mouse TRAPP-related protein is involved in pigmentation

We identified a new spontaneous recessive mutation in the mouse, mhyp (mosaic hypopigmentation), in a screen for novel proviral integration sites in a multiple ecotropic provirus mapping stock. Integration of an 8.4-kb retrovirus results in mosaic loss of coat pigment in mhyp homozygotes. Patchy loss of pigmentation in the retinal pigmented epithelial layer of the eye with abnormal melanosomes is also evident. We mapped mhyp to mouse chromosome 7 and cloned the underlying gene. mhyp is a defect in the Trappc6a gene. Expression of Trappc6a is markedly diminished in mhyp homozygotes. The normal protein, TRAPPC6A, is a subunit of the TRAPP (transport protein particle) I and II complexes. While TRAPP complexes are essential for ER-to-Golgi and intra-Golgi vesicle trafficking in yeast, TRAPP subunits participate in additional, including post-Golgi, transport events in mammals. The data implicate mammalian TRAPPC6A in vesicle trafficking during melanosome biogenesis.     

A mouse linkage testing stock possessing multiple copies of the endogenous ecotropic murine leukemia virus genome

A new linkage testing stock of the laboratory mouse has been constructed. The stock, designated MEV (multiple ecotropic provirus), was developed by inbreeding and selection beginning with the cross of strains C58/J and AKXD-14. Eleven different murine leukemia virus (MuLV) proviruses have been fixed in the MEV/1Ty strain. Nine of these can be uniquely identified by Southern blotting of PvuII-digested DNA and probing with a cloned fragment of the ecotropic viral genome. Two proviruses had been mapped previously to chromosome 7, while single proviruses had been mapped to chromosomes 2, 9, and 11. The mapping of six additional proviruses, derived from C58/J, to chromosomes 1, 3, 5, 10, 18, and 19 is described. Another C58/J provirus was mapped to chromosome 8 and proved to be identical to the previously mapped C58v-1 virus inducibility gene of strain C58/Lw. Three dominant visible markers, hammer-toe (Hm), steel (Sl), and caracul-J (CaJ), located on chromosomes 5, 10, and 15, respectively, have been introduced onto the MEV genetic background by repeated backcrosses to provide additional linkage markers. It is estimated that approximately 50% of the genome can be screened by scoring 50 fully informative gametes from a linkage cross of the MEV-Hm, -Sl, -CaJ stock for the combination of viral and visible markers. A strategy for efficiently mapping new recessive visible mutations by pooling tissues for DNA extraction from mutant homozygotes among F2 progeny is described. Ways of further improving the MEV stock are discussed. The location of the Myb proto-oncogene is defined relative to Sl and one of the C58/J proviruses on chromosome 10.     

Establishment of an albino strain of the bitterling Tanakia signifer (Pisces, Cyprinidae)

An albino strain of the bitterling Tanakia signifer (Pisces, Cyprinidae, Acheilognathinae) was established through interbreeding using an albino male selected from among the offspring produced from the spawning of 18 wild-caught individuals. This is the first report of albinism in this species. Progeny tests demonstrated that inheritance of the trait follows the expected pattern for a simple autosomal recessive. A stock of 200+ individuals is currently being held at the Kannonzaki Nature History Museum, Japan.     

Genetic analysis of the BB/W diabetic rat

A large colony of BB/W diabetic rats has been developed as a research model for insulin dependent, type 1 diabetes mellitus. The foundation stock had 8% diabetics which appeared in a sporadic manner. The Worcester (W) colony was inbred by brother X sister matings for 11 generations and the proportion of diabetics increased to over 50%. The age of detection varies from 46 to 250 days. For selection purposes, classification was made at 120 days, which means that 15 to 20% potential diabetics were classified as normal. Evidence from different analyses indicates that the inheritance of diabetes is by a recessive gene or gene cluster with 50% penetrance at 120 days. The selection of breeding stock from diabetic parents raised the proportion of diabetics produced by two normal parents from 12 to 43%. Diallel tests show that diabetic and normal offspring of two diabetic parents have the same diabetic genotype. Outcrosses to other strains of rat indicate that the trait is transferred as a recessive with only 3% diabetics recovered in the F2 where noninbred BB stock was used as the diabetic source, and 36% where partially inbred BB/W was used as the diabetic parent. Since the proportion of diabetics produced by all types of crosses has changed, and may continue to change with changes in the genetic background, we have used the operational term penetrance to describe the frequency of diabetes in individuals homozygous for the diabetes gene cluster. At present the penetrance at 120 days is 59% in the BB/W colony.     

The inheritance of a wingless character in the 2spot ladybird (Adalia bipunctata)

A viable wingless 2spot ladybirdAdalia bipunctata (L.) was found in the wild. Breeding through four generations revealed that the wingless trait was controlled by a recessive allele which displays variable levels of expression. The wingless ladybird is discussed in relation to its potential as a biocontrol agent. One ladybird also occurred in this stock which is suggestive of a supergene controlling the colour polymorphism in this species.     

The existence of species rests on a metastable equilibrium between inbreeding and outbreeding. An essay on the close relationship between speciation, inbreeding and recessive mutations

Background

Speciation corresponds to the progressive establishment of reproductive barriers between groups of individuals derived from an ancestral stock. Since Darwin did not believe that reproductive barriers could be selected for, he proposed that most events of speciation would occur through a process of separation and divergence, and this point of view is still shared by most evolutionary biologists today.

Results

I do, however, contend that, if so much speciation occurs, the most likely explanation is that there must be conditions where reproductive barriers can be directly selected for. In other words, situations where it is advantageous for individuals to reproduce preferentially within a small group and reduce their breeding with the rest of the ancestral population. This leads me to propose a model whereby new species arise not by populations splitting into separate branches, but by small inbreeding groups "budding" from an ancestral stock. This would be driven by several advantages of inbreeding, and mainly by advantageous recessive phenotypes, which could only be retained in the context of inbreeding. Reproductive barriers would thus not arise as secondary consequences of divergent evolution in populations isolated from one another, but under the direct selective pressure of ancestral stocks. Many documented cases of speciation in natural populations appear to fit the model proposed, with more speciation occurring in populations with high inbreeding coefficients, and many recessive characters identified as central to the phenomenon of speciation, with these recessive mutations expected to be surrounded by patterns of limited genomic diversity.

Conclusions

Whilst adaptive evolution would correspond to gains of function that would, most of the time, be dominant, this type of speciation by budding would thus be driven by mutations resulting in the advantageous loss of certain functions since recessive mutations very often correspond to the inactivation of a gene. A very important further advantage of inbreeding is that it reduces the accumulation of recessive mutations in genomes. A consequence of the model proposed is that the existence of species would correspond to a metastable equilibrium between inbreeding and outbreeding, with excessive inbreeding promoting speciation, and excessive outbreeding resulting in irreversible accumulation of recessive mutations that could ultimately only lead to extinction.

Reviewer names

Eugene V. Koonin, Patrick Nosil (nominated by Dr Jerzy Jurka), Pierre Pontarotti     

Monoploids in Zea mays L. following crosses with untreated and X-rayed pollen

Monoploids in Zea mays L. occur spontaneously among individual diploid seedlings. Plants with the gametic chromosome number have also been detected among members of multiple seedlings of maize and numerous other species of angiosperms. Previous reports disclosed that Xirradiation of the pollen successfully stimulated reduced parthenogenesis in some other angiosperms, but the results of X-ray treatment were inconclusive in maize. Therefore, a tester stock of maize homozygous for lg _land gl _l was crossed with pollen from inbred CI3A, carrying the dominant alleles. The pollen was exposed to 0, 1000, 2000, and 4000r units of X rays. chromosome counts were made from root tips of plants exhibiting both recessive phenotypes to establish the frequencies of monoploids in the control and X₁ populations.Monoploids were more abundant among the individual seedlings from crosses with untreated pollen than in the X₁ populations. X irradiation of the pollen is not a feasible method for the induction of monoploids in maize. The X-ray treatments greatly increased the frequency of multiple seedlings, and deficiencies were numerous among them. The members of a set of multiple seedlings were always genetically identical, and no monoploid members occurred. It is concluded that the induced deficiencies caused atypical development resulting in zygotic or embryonic cleavage.Scientific Article No. A2070, Contribution No. 5023 of the Maryland Agricultural Experiment Station, Department of Botany.     

Electrophoretic variation in multiple recessive tester, T, stock mice

The multiple recessive tester stock, homozygous for seven recessive visible markers, has been used since the 1950s in the specific locus test of mutagenicity in the mouse. The stock was developed by W.L. Russell in Oak Ridge, sent to the MRC Radiobiology Unit (Harwell) in 1953 and then passed to Research Triangle Institute (RTI) in 1988. Stocks are maintained by random mating in all three centres. and in addition stocks that have been selected for homozygosity at certain enzyme and protein markers are kept at both Harwell and RTI. The extent of electrophoretic variation was investigated in the random bred tester stocks at Harwell in 1981 and 1990, and in both random bred and fixed tester stocks at RTI in 1990. Altogether 44 loci were scored and eight of these (Acy-1, Es-3, Gpi-1, Hba, Hbb, Idh-1, Mod-1 and Pgd) have been polymorphic in one or more colonies at various times. Three loci (Es-3, Hbb and Mod-1) had low levels of polymorphism in 1981 and had become monomorphic by 1990. Despite this slight loss of variation, overall the tester stocks show considerable variability. The proportion of polymorphic loci and mean heterozygosity is of the same order of magnitude as island populations of wild mice or other isolated random bred laboratory populations. Contamination of tester stocks with other stocks can be ruled out, and thus tester stocks can be considered to be characteristic island populations. The retention of an appreciable amount of genetic variability in tester stocks is of practical importance in designing new mutation tests involving these mice. When using these stocks, care must be taken to ensure that they are homozygous for the loci under test.     

Dose-response relationships and R.B.E. values of dominant lethals induced by X-rays and 1.5 MeV neutrons in prophase-1 oocytes and in mature sperm of the two-spotted spider mite Tetranychus urticae Koch (acari, tetranychidae)

Mature sperm and prophase-1 oocytes of Tetranychus urticae Koch were irradiated with 250-kVp X-rays or 1.5 MeV fast neutrons. The X-ray doses ranged from 0.5 to 24.0 krad, and those of the fast neutrons from 0.1 to 16.0 krad. The genetic endpoint measured was lethality, expressed in the stages from egg to adulthood in the F1 progeny. The frequency of recessive lethals in female germ cells was estimated by comparing survival of fertilized versus unfertilized F1 eggs, after irradiation with the same dosage. X-Rays induce dominant lethals in prophase-1 oocytes by the action of both single hits on single targets and multiple hits on multiple targets. 1.5-MeV neutrons induce these effects predominantly by the action of multiple tracks on multiple targets. Dominant lethals were induced in mature sperm by X-rays and by fast neutrons by the action of both single hits on single targets and multiple hits on multiple targets. Both for prophase-1 oocytes and for mature sperm the low R.B.E. value corresponded with the relatively large multiple-target component of induction of dominant lethals by fast neutrons. The nature of dominant lethality in relation to the kinetochore organization of the chromosome is discussed. A non-linear trend in the dose--effect relationship was observed for both X-rays and fast neutrons for the estimated frequency of recessive lethals induced in prophase-1 oocytes. X-Rays were more effective than neutrons in inducing recessive lethals in prophase-1 oocytes at doses lower than 3 krad.     

A genetical model for vitiligo.

A genetical model is found to provide a good fit to family data on vitiligo. The model postulates that recessive alleles at a set of four unlinked diallelic loci are involved in the causation of the disorder. Under this multiple recessive homozygosis model, for normal X affected families ascertained through the affected parent, the expected segregation probability is .063; the estimated value is 0.53, which is not significantly different from the expected value. For normal X normal families ascertained through an affected offspring, the expected segregation probability is .037; the estimated value is .04.     

Mutagen-sensitive mutants in Drosophila melanogaster: effects on premutational damage.

Drosophila melanogaster males from a Basc stock were mutagenized with either X-rays, ethyl methanesulfonate (EMS), or nitrogen mustard (HN2). Groups of identically treated males were crossed to different types of female. Sex-linked recessive lethals were scored as a genetic end point. The females used were homozygous for X-chromosomal mutations (mus(1)101D1, mus(1)104D1, mei-9 or mei-41D5) which lead to defective DNA repair and which increase the mutagen sensitivity of larvae. Females from a white stock with normal DNA repair capacities served as controls. The premutational lesions induced in mature sperm are only processed after insemination by the maternal enzyme systems present in the oocytes. Differences in the efficiency of the processing of lesions can lead to maternal effects on the frequency of mutations recovered from mutagenized sperm. It was found that, with the exception of mus(1)104D1, all mutants analysed significantly modify the mutation fixation of one or more types of premutational lesions. The most drastic effect is found with the mus(1)101D1 stock in which HN2-induced DNA cross-links do not lead to sex-linked recessive lethals. It is assumed that mus(1)101D1 is defective in an early step of DNA cross-link repair. Our first set of data clearly demonstrates that the study of maternal effects in Drosophila is an efficient tool to analyse the in vivo function of repair mutations on chemically induced mutagenesis.     

The genetics of abnormal abdomen, incomplete abdomen, and bobbed in Drosophila buzzatii

Five stocks of Drosophila buzzatii with superficially similar abdominal disruptions including partial tergite and sternite loss were isolated by inbreeding. Three of the stocks have indistinguishable phenotypes, the inheritance of which is maternally influenced. This phenotype and its mode of inheritance bear similarities with those of Abnormal abdomen in D. melanogaster. The phenotype in the fourth stock is slightly different and is due to a single autosomal recessive gene, which we denote incomplete abdomen. In the fifth stock the trait is limited to females, and in appearance and mode of inheritance resembles bobbed in D. melanogaster. Furthermore, only in this stock are rDNA deletions evident. The combined frequencies of the three types of abdominal aberration were found to be around 1% in several samples from wild and laboratory populations of D. buzzatii.     

Alternative Phenotypic States in Genomically Identical Cells: Interstock Genetics of a Trichocyst Phenotype in PARAMECIUM TETRAURELIA

The trichocysts of most wild stocks of Paramecium tetraurelia discharge en masse in response to picric acid. In most nonresponding wild stocks, the defective phenotype is simply determined by a single recessive gene difference from the standard wild type, stock 51. However, two wild stocks, 146 and 148, which are completely homozygous at all loci, express either a nondischarge, ND, or discharge, DI, phenotype. In stock 146, both ND and DI sublines generally reproduce true to type, but observed changes are highly biased. Changes from ND to DI occur more than ten times as often as changes from DI to ND. After conjugation between ND and DI cells, genomically identical exconjugant lines from the ND parent may be either ND or DI, while those from the DI parent invariably remain DI.—Interstock crosses between stocks 146 and 51 indicate that stock 146 possesses a recessive gene, nd146, which, when homozygous in stock 51 background, produces a distinct nondischarge phenotype, KO. Crosses between stock 146 and KO phenotype nd146 homozygotes in stock 51 background demonstrate that stock 146 possesses a dominant gene, M-nd146, which modifies the defect of nd146 homozygotes, resulting in either the ND or DI phenotype. The two loci, M-nd146 and nd146, are linked and estimated to be 5.3 centiMorgans apart. Stock 148 has the same alleles as stock 146 at these loci.—Presumably M-nd146 is involved in the dual phenotypic states in stock 146, but M-nd146 nd146 homozygotes backcrossed into stock 51 are invariably discharging. The possibility that the original ND state is independent of these genes is discussed and is regarded as unlikely. The phenotypic and genetic relationship discovered in these stocks should remind population biologists that phenotypic and genotypic variability do not always have a simple relationship. The nature and frequency of epistasis in the highly inbreeding P. tetraurelia are reviewed.     

Recessive black is allelic to the yellow plumage locus in Japanese quail and associated with a frameshift deletion in the ASIP gene

The recessive black plumage mutation in the Japanese quail (Coturnix japonica) is controlled by an autosomal recessive gene (rb) and displays a blackish-brown phenotype in the recessive homozygous state (rb/rb). A similar black coat color phenotype in nonagouti mice is caused by an autosomal recessive mutation at the agouti locus. An allelism test showed that wild type and mutations for yellow, fawn-2, and recessive black in Japanese quail were multiple alleles (*N, *Y, *F2, and *RB) at the same locus Y and that the dominance relationship was Y*F2 > Y*Y > Y*N > Y*RB. A deletion of 8 bases was found in the ASIP gene in the Y*RB allele, causing a frameshift that changed the last six amino acids, including a cysteine residue, and removed the normal stop codon. Since the cysteine residues at the C terminus are important for disulphide bond formation and tertiary structure of the agouti signaling protein, the deletion is expected to cause a dysfunction of ASIP as an antagonist of alpha-MSH in the Y*RB allele. This is the first evidence that the ASIP gene, known to be involved in coat color variation in mammals, is functional and has a similar effect on plumage color in birds.     

Prospects for using multimarker dihaploid lines for mapping the barley genome

Model population of spring barley Oregon Wolfe Pack dihaploid lines, derived from F1 of cross between dominant marker stock and recessive line, was studied on presence of morphological markers. For detection of DNA variability RAPD-analysis of these genotypes was carried out. Polymorphic fragment correlating with morphological trait was detected using primer P89.     

Mutagenicity of sumithion tested in Drosophila somatic and germ cells

Sumithion, a broad-spectrum insecticide, was tested for its mutagenicity in the Drosophila wing-spot test and sex-linked recessive lethal test. Strains carrying the recessive mutant markers mwh and flr3 in their third chromosomes, expressed phenotypically as multiple trichomes or thickened and misshapen wing hairs in the adult wings, were used in the wing-spot test. Larvae transheterozygous for these markers were exposed to the insecticide in instant food and the sex-linked recessive lethal test was performed by the standard technique using the Basc strain. The compound is mutagenic in the wing primordial cells and induces recombination at high doses. Further, the frequency of induction of sex-linked recessive lethals is significant only at high treatment doses.     

Refsum's disease (heredopathia atactica polyneuritiformis)

The formal genetics of 37 patients suffering from Refsum's disease is reviewed. The absence of the disease in parents and relatives excepts sibs of the propositi, the high parental consanguinity rate, and the observed number of affected sibs are in agreement with the assumption of an inheritance by a rare autosomal recessive gene. The geographical distribution of the patients suggests that most of them may have originated from one Scandinavian stock.     

yellow 0, a marker for low body weight in Drosophila melanogaster

Marker-assisted selection(MAS) is an important modern breeding technique,but it has been found that the effect of the markers for quantitative trait loci(QTL) is inconsistent,leading in some cases to MAS failure and raising doubts about its effectiveness.Here the model organism Drosophila melanogaster was employed to study whether an effective marker could be found and applied to MAS.We crossed the stock carrying the y0 marker(a recessive mutation allele of the yellow gene on the X chromosome) with three ot...     

Highly Branched Phenotype of the Petunia dad1-1 Mutant Is Reversed by Grafting

The recessive dad1-1 allele conditions a highly branched growth habit resulting from a proliferation of first- and second-order branches. Unlike the wild-type parent, which has lateral branching delayed until the third or fourth leaf node distal to the cotyledons, dad1-1 initiates lateral branching from each cotyledon axil. In addition to initiating lateral branching sooner than the wild type, dad1-1 sustains branching through more nodes on the main shoot axis than the wild type. In keeping with a propensity for branching at basal nodes, dad1-1 produces second-order branches at the proximal-most nodes on first-order branches and small shoots from accessory buds at basal nodes on the main shoot axis. Additional traits associated with the mutation are late flowering, adventitious root formation, shortened internodes, and mild leaf chlorosis. Graft studies show that a dad1-1 scion, when grafted onto wild-type stock, is converted to a phenotype resembling the wild type. Furthermore, a small wild-type interstock fragment inserted between a mutant root stock and a mutant scion is sufficient to convert the dad1-1 scion from mutant to a near wild-type appearance. The recessive dad1-1 phenotype combines traits associated with cytokinin overexpression, auxin overexpression, and gibberellin limitation, which suggests a complex interaction of hormones in establishing the mutant phenotype.