Mutation modification with multiplicative fertility selection

Two diallelic loci in an infinite panmictic population of diploid individuals are modelled. The A/a locus is subject to unidirectional mutation and either multiplicative fertility selection or, equivalently, sex-asymmetric viability selection. The M/m locus acts as a selectively neutral modifier of the mutation rate at A/a. The loci recombine at rate R. If the M/m locus is initially monomorphic, and the A/a locus has reached equilibrium, the fate of a new modifier allele is found to depend not just on its relative effect on mutation but also upon the linkage, R. Each initial equilibrium may be characterized by a critical value of the recombination rate, R*. If 0 less than R* less than 0.5, a sufficiently small "down" modifier of the mutation rate will invade the population when R less than R* whereas a sufficiently small "up" modifier will succeed when R greater than R*. If R* less than 0 or R* greater than 0.5, only mutation reduction may occur. Numerical analysis of 56,000 sample equilibria indicates that mutation rates may be increased, but only when the selection regime is such that the A/a locus would remain polymorphic in the absence of mutation.     

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.     

Melanocortin receptor 1 (MC1R) mutations and coat color in pigs.

The melanocortin receptor 1 (MC1R) plays a central role in regulation of eumelanin (black/brown) and phaeomelanin (red/yellow) synthesis within the mammalian melanocyte and is encoded by the classical Extension (E) coat color locus. Sequence analysis of MC1R from seven porcine breeds revealed a total of four allelic variants corresponding to five different E alleles. The European wild boar possessed a unique MC1R allele that we believe is required for the expression of a wild-type coat color. Two different MC1R alleles were associated with the dominant black color in pigs. MC1R*2 was found in European Large Black and Chinese Meishan pigs and exhibited two missense mutations compared with the wild-type sequence. Comparative data strongly suggest that one of these, L99P, may form a constitutively active receptor. MC1R*3 was associated with the black color in the Hampshire breed and involved a single missense mutation D121N. This same MC1R variant was also associated with EP, which results in black spots on a white or red background. Two different missense mutations were identified in recessive red (e/e) animals. One of these, A240T, occurs at a highly conserved position, making it a strong candidate for disruption of receptor function.     

Mutations in SLC45A2 cause plumage color variation in chicken and Japanese quail

S*S (Silver), S*N (wild type/gold), and S*AL (sex-linked imperfect albinism) form a series of alleles at the S (Silver) locus on chicken (Gallus gallus) chromosome Z. Similarly, sex-linked imperfect albinism (AL*A) is the bottom recessive allele at the orthologous AL locus in Japanese quail (Coturnix japonica). The solute carrier family 45, member 2, protein (SLC45A2), previously denoted membrane-associated transporter protein (MATP), has an important role in vesicle sorting in the melanocytes. Here we report five SLC45A2 mutations. The 106delT mutation in the chicken S*AL allele results in a frameshift and a premature stop codon and the corresponding mRNA appears to be degraded by nonsense-mediated mRNA decay. A splice-site mutation in the Japanese quail AL*A allele causes in-frame skipping of exon 4. Two independent missense mutations (Tyr277Cys and Leu347Met) were associated with the Silver allele in chicken. The functional significance of the former mutation, associated only with Silver in White Leghorn, is unclear. Ala72Asp was associated with the cinnamon allele (AL*C) in the Japanese quail. The most interesting feature concerning the SLC45A2 variants documented in this study is the specific inhibition of expression of red pheomelanin in Silver chickens. This phenotypic effect cannot be explained on the basis of the current, incomplete, understanding of SLC45A2 function. It is an enigma why recessive null mutations at this locus cause an almost complete absence of both eumelanin and pheomelanin whereas some missense mutations are dominant and cause a specific inhibition of pheomelanin production.     

Association of a Glu92Lys substitution in MC1R with extended brown in Japanese quail (Coturnix japonica)

We investigated melanocortin 1 receptor (MC1R) as a candidate locus for the Extended brown phenotype in quail, in which there is a general darkening throughout the plumage. An initial screen of variation in MC1R in Extended brown and in wild-type quails revealed two polymorphic non-synonymous sites. One of these sites, a G-to-A substitution leading to a Glu92Lys mutation, was perfectly associated with plumage phenotype; all Extended brown birds were homozygous for Lys92. Co-segregation of the Glu92Lys mutation with the Extended brown phenotype was confirmed in 24 progeny of an E/e(+) x E/e(+) cross. Glu92Lys is likely to be the causative mutation for the increased melanism in Extended brown, given that the same mutation is associated with melanic plumage in many breeds of domestic chicken, as well as in a wild passerine bird (the bananaquit, Coereba flaveola) and laboratory mice. Interestingly, the increase in melanization with the Glu92Lys mutation is less marked in quails than in most other birds and mammals. Phylogenetic results indicate that the Glu92Lys mutation has independently occurred in quail and chicken lineages.     

Shankless, a new mutation on chromosome 2 in the chicken

A mutant condition characterized by absence of shanks is invariably present in chickens that are homokaryotypic for an X-ray-induced pericentric inversion to chromosome 2. The mutation was studied in 260 embryos at 19 days of incubation. Embryos produced from matings of parents with and without the inversion were karyotyped and their skeletons observed and measured. The mutant phenotype, which was seen in all birds homokaryotypic for the inversion, is characterized by malformed and reduced metacarpals, absence of tarsometatarsal shanks, increased tibia length, extra bones in digits two, three, and four, and fusion of proximal phalanges. Heterokaryotypic and homokaryotypic normal embryos had normal phenotypes, but the length of metacarpals was slightly reduced in heterokaryotypes. The primary effect of the mutation is to cause misplacement, malformation, and underdevelopment of metatarsals II, III, and IV. The recessive mutation, located in the proximal region of chromosome 2, has been designated shankless (shl).     

Association of a single-nucleotide substitution in TYRP1 with roux in Japanese quail (Coturnix japonica)

We investigated TYRP1 as a candidate locus for the recessive, sex-linked roux (br(r)) phenotype in Japanese quail. A screen of the entire coding sequence of TYRP1 in roux and wild-type quail revealed a non-synonymous T-to-C substitution in exon 3, leading to a Phe282Ser mutation. This was perfectly associated with plumage phenotype: all roux birds were homozygous for Ser282. Co-segregation of the Phe282Ser mutation with the roux phenotype was confirmed in three br(r)/BR+ x br(r)/- backcrosses. We found no significant difference in TYRP1 expression between roux and wild-type birds, suggesting that this association is not due to linkage disequilibrium with an unknown regulatory mutation. In addition, the Phe282 amino acid appears to be of functional significance, as it is highly conserved across the vertebrates. This is the first demonstration that TYRP1 has a role in pigmentation in birds.     

Genetic mapping of a 7R Al tolerance QTL in triticale (x Triticosecale Wittmack)

Triticale (x Triticosecale Wittmack) is a relatively new cereal crop. In Poland, triticale is grown on 12 % of arable land (http://www.stat.gov.pl). There is an increasing interest in its cultivation due to lowered production costs and increased adaptation to adverse environmental conditions. However, it has an insufficient tolerance to the presence of aluminum ions (Al³⁺) in the soil. The number of genes controlling aluminum tolerance in triticale and their chromosomal location is not known. Two F2 mapping biparental populations (MP1 and MP15) segregating for aluminum (Al) tolerance were tested with AFLP, SSR, DArT, and specific PCR markers. Genetic mapping enabled the construction of linkage groups representing chromosomes 7R, 5R and 2B. Obtained linkage groups were common for both mapping populations and mostly included the same markers. Composite interval mapping (CIM) allowed identification of a single QTL that mapped to the 7R chromosome and explained 25 % (MP1) and 36 % (MP15) of phenotypic variation. The B1, B26 and Xscm150 markers were 0.04 cM and 0.02 cM from the maximum of the LOD function in the MP1 and MP15, respectively and were highly associated with aluminum tolerance as indicated by Kruskal–Wallis nonparametric test. Moreover, the molecular markers B1, B26, Xrems1162 and Xscm92, previously associated with the Alt4 locus that encoded an aluminum-activated malate transporter (ScALMT1) that was involved in Al tolerance in rye (Secale cereale) also mapped within QTL. Biochemical analysis of plants represented MP1 and MP15 mapping populations confirmed that the QTL located on 7R chromosome in both mapping populations is responsible for Al tolerance.     

The Genetics of the Dras3-Roughened-Ecdysoneless Chromosomal Region (62b3-4 to 62d3-4) in Drosophila Melanogaster: Analysis of Recessive Lethal Mutations

The genetic organization of interval 62B3-4 to 62D3-4 on the Drosophila third chromosome was investigated. The region (designated DRE) includes four known loci: Roughened (R; 3-1.4), defined by a dominant mutation disrupting eye morphology; the nonvital locus Aprt, structural gene for adenine phosphoribosyltransferase; Dras3, a homolog of the vertebrate ras oncogene; and 1(3)ecdysoneless (1(3)ecd), a gene that has been implicated in the regulation of larval molting hormone (ecdysteroid) synthesis. Overlapping chromosomal deletions of the region were generated by gamma-ray-induced reversion of the R mutation. Recessive lethal mutations were isolated based upon failure to complement the recessive lethality of Df(3L)RR2, a deletion of the DRE region that removes 16-18 polytene chromosome bands. A total of 117 mutations were isolated following ethyl methanesulfonate and gamma-ray mutagenesis. These and two additional define 13 lethal complementation groups. Mutations at two loci were recovered at disproportionately high rates. One of these loci is preferentially sensitive to radiation-induced mutational alterations. Additionally, an unusually low recovery rate for cytologically detectable rearrangement breakpoints within the gamma-ray-sensitive locus suggests that an interval of the DRE region closely linked to the R locus may be dominantly sensitive to position effects. Lethal phase analysis of mutant hemizygotes indicates that a high proportion of DRE-region loci (11 of 13) are necessary for larval development. Mutations in five loci cause predominantly first-instar larval lethality, while mutations in four other loci cause predominantly second-instar lethality. Mutations in two loci cause late-larval lethality associated with abnormal imaginal disc development. A temperature-sensitive allele of one newly identified complementation group blocks ecdysteroid-induced pupariation. This developmental block is overcome by dietary 20-hydroxyecdysone, suggesting that a second locus in the region in addition to l(3)ecd may play a role in the regulation of late larval ecdysteroid levels.     

Pyruvate oxidase is a determinant of Avery's rough morphology

In pioneering studies, Avery et al. identified DNA as the hereditary material (A. T. Avery, C. M. MacLeod, and M. McCarty, J. Exp. Med. 79:137-158, 1944). They demonstrated, by means of variation in colony morphology, that this substance could transform their rough type 2 Streptococcus pneumoniae strain R36A into a smooth type 3 strain. It has become accepted as fact, from modern textbook accounts of these experiments, that smooth pneumococci make capsule, while rough strains do not. We found that rough-to-smooth morphology conversion did not occur in rough strains R36A and R6 when the ability to synthesize native type 2 capsule was restored. The continued rough morphology of these encapsulated strains was attributed to a second, since-forgotten, morphology-affecting mutation that was sustained by R36A during strain development. We used a new genome-PCR-based approach to identify spxB, the gene encoding pyruvate oxidase, as the mutated locus in R36A and R6 that, with unencapsulation, gives rise to rough colony morphology, as we know it. The variant spxB allele of R36A and R6 is associated with increased cellular pyruvate oxidase activity relative to the ancestral strain D39. Increased pyruvate oxidase activity alters colony shape by mediating cell death. R36A requires a wild-type spxB allele for the expression of smooth type 2 morphology but not for the expression of smooth type 3 morphology, the phenotype monitored by Avery et al. Thus, the mutated spxB allele did not impact their use of smooth morphology to identify the transforming principle.     

Phenotypic Suppression of the Gibberellin-Insensitive Mutant (gai) of Arabidopsis

The semidominant gibberellin-insensitive (gai) mutant of Arabidopsis thaliana shows impairment in multiple responses to the plant hormone gibberellin A3, which include effects on seed germination, stem elongation, apical dominance, and rapid flowering in short days. Results presented here show that the gai mutation also interferes with development of fertile flowers in continuous light. Mu-tagenesis of the gai mutant resulted in recovery of 17 independent mutants in which the gibberellin-insensitive phenotype is partially or completely suppressed. Sixteen of the suppressor mutations act semidominantly to restore gibberellin responsiveness. One representative of this class, the gar1 mutation, could not be genetically separated from the gai locus and is proposed to cause inactivation of the gai gene. The exceptional gar2 mutation partially suppresses the gai phenotype, is completely dominant, and is not linked to the gai locus. The gar2 mutation may define a new gene involved in gibberellin signaling. A recessive allele of the spindly (SPY) locus, spy-5, was also found to partially suppress the gai mutant phenotype.     

Polymorphisms of alpha-1-acid (orosomucoid), alpha-2-HS-glycoproteins and alpha-1-B among the Parsis of India.

Genetic polymorphisms of plasma alpha 1-acid glycoprotein (oro-somucoid, ORM), alpha 2-HS-glycoprotein (A2HS) and alpha 1-B-glycoprotein (alpha 1B) were studied in a group of Parsis in Bombay, India. The frequencies of ORM1*1, ORM1*2 and ORM1*3 were found to be 0.636, 0.356 and 0.008, respectively. A2HS*1, A2HS*2 and A2HS*3 frequencies were 0.855, 0.135 and 0.010, while the frequencies of A1B*1 and A1B*2 were 0.881 and 0.119, respectively. The phenotype distribution at all three loci was at Hardy-Weinberg equilibrium. The ORM2 locus was monomorphic in the Parsis.     

Unmelanized plumage patterns in Old World leaf warblers do not correspond to sequence variation at the melanocortin-1 receptor locus (MC1R)

Evolutionary changes in patterns and coloration of plumage are likely to represent a major mechanism for speciation among birds, yet the molecular basis for such changes remains poorly understood. Recently much attention has focused on the melanocortin-1 receptor (MC1R) as a candidate locus for determining the level and extent of epidermal melanin deposition. We tested the hypothesis that MC1R sequence variation is associated with interspecific variation in unmelanized plumage pattern elements in Old World leaf warblers (genus Phylloscopus). This genus is characterized by a variety of plumage patterns that nonetheless vary along similar lines. Species vary in the presence or absence of pale (unmelanized) pattern elements against a dark background, and these patterns are used in species recognition and courtship. We sequenced most of the MC1R coding region for eight Phylloscopus species, representing the full range of plumage patterns found in this genus. Although MC1R sequence varied among species, this variation was not related to melanin-based plumage variation. Rather, evolution of this locus in these birds appears to be conservative. Ratios of nonsynonymous to synonymous substitutions (dN/dS) were consistently low, suggesting that strong purifying selection has operated at this locus, and likelihood ratio testing revealed no evidence of variable selective pressures among lineages or across codons. Adaptive evolution at MC1R may be constrained by the adaptive importance of plumage pattern elements in this genus.     

Evolution of an avian pigmentation gene correlates with a measure of sexual selection

The extravagant plumage traits of male birds are a favourite example of sexual selection. However, to date the units that selection is acting upon, the genes themselves have been a 'black box'. Here, we report evidence of change driven by sexual selection at a pigmentation gene locus in the galliform birds. Across species, we find a correlation between the rate of amino acid change (dN/dS) at this locus (MC1R) and the degree of sexual dichromatism, which we use as a measure of the strength of sexual selection. There is no evidence for a similar pattern in any of five other loci (four candidate and one control locus). This is consistent with previous work on colour polymorphisms and suggests that MC1R may be a key target for selection acting on plumage colour. The pattern of selection at MC1R seems to be consistent with the continuous or cyclical evolution of traits and preferences that is the outcome of several Fisherian and good-genes models of sexual selection. In contrast, we found no support for models of sexual selection that predict an increase in purifying selection as a result of purging of deleterious mutations or for models that predict an increased rate of mutation in association with stronger sexual selection.     

Transfer of leaf rust and stem rust resistance genes from Triticum triaristatum to durum and bread wheats and their molecular cytogenetic localization.

Six accessions of Triticum triaristatum (Willd) Godr. &Gren. (syn. Aegilops triaristata) (6x, UUMMUnUn), having good resistance to both leaf rust (Puccinia recondita f.sp. tritici Rob. ex Desm) races and stem rust (P. graminis f.sp. tritici Eriks. &Henn.) races, were successfully crossed with both susceptible durum wheats (T. turgidum var. durum L., 2n = 28, AABB) and bread wheats (T. aestivum, 2n = 42, AABBDD). In some crosses, embryo rescue was necessary. The T. triaristatum resistance was expressed in all F1 hybrids. Backcrossing of the F1 hybrids to their wheat parents to produce BC1F1 plants was more difficult (seed set 0-7.14%) than to produce F1 hybrids (seed set 12.50-78.33%). The low female fertility of the F1 hybrids was due to low chromosome pairing. Only gametes with complete or nearly complete genomes from the F1 hybrids were viable. In BC2F4 populations from the cross MP/Ata2//2*MP, monosomic or disomic addition lines (2n = 21 II + 1 I or 22 II) with resistance to leaf rust race 15 (IT 1) were selected. In BC2F2 populations from the crosses CS/Ata4//2*MP and MP/Ata4//2*MP, monosomic or disomic addition lines with resistance to either leaf rust race 15 or stem rust race 15B-1 (both IT 1) were selected. Rust tests and cytology on the progeny of the disomic addition lines confirmed that the genes for rust resistance were located on the added T. triaristatum chromosomes. The homoeologous groups of the T. triaristatum chromosomes in the addition lines from the crosses MP/Ata2//2*MP, CS/Ata4//2*MP, and MP/Ata4//2*MP were determined to be 5, 2, and 7, respectively, through the detecting of RFLPs among genomes using a set of homoeologous group specific wheat cDNA probes. The addition lines with resistance to leaf rust race 15 from the crosses MP/Ata2//2*MP and CS/Ata4//2*MP were resistant to another nine races of leaf rust and the addition line with resistance to stem rust race 15B-1 from the cross MP/Ata4//2*MP was resistant to another nine races of stem rust as were their T. triaristatum parents. Since such genes provide resistance against a wide spectrum of rust races they should be very valuable in wheat breeding for rust resistance.     

Genetic analyses of plumage color mutations on the Z chromosome of Japanese quail

Genetic analyses were performed with four sex-linked plumage color mutations (roux, brown, imperfect albino, and cinnamon) in Japanese quail (Coturnix japonica). Roux and brown quail have similar plumage color, but plumage of roux quail is paler. Pure, F1 and F2 matings were carried out with roux and brown stocks, and 357, 338, and 273 progeny with either roux or brown plumage color were obtained from each mating type, respectively. These allelism tests showed that mutations for roux and brown colors were alleles (*R and *B) from the same locus BR, and that BR*B was dominant over BR*R. Two alleles at the AL locus, AL*A (imperfect albino) and AL*C (cinnamon) were used to estimate the recombination frequency between the BR and AL loci on the Z chromosome. It was estimated to be 38.1+/-1.0% based on 4615 chicks from the test crosses.     

Recurrent mutation, gene conversion, or recombination at the human phenylalanine hydroxylase locus: evidence in French-Canadians and a catalog of mutations.

The codon 408 mutation (CGG----TGG, Arg----Trp) in exon 12 of the phenylalanine hydroxylase (PAH) gene occurs on haplotype 1 in French-Canadians; elsewhere this mutation (R408W) occurs on haplotype 2. A CpG dinucleotide is involved. The finding is compatible with a recurrent mutation, gene conversion, or a single recombination between haplotypes 2 and 1. A tabulation of 20 known mutations at the PAH locus reveals three instances of putative recurrent mutation.