Scholarly Literature
This is an aggregation of scholarly literature from peer-reviewed journals, bioRxiv , medRxiv and arXiv preprint servers focused on natural and engineered selfish genetic elements and genetic biocontrol. New citations are added as they appear. This content is intended for anyone interested in the scholarly literature on gene drive and genetic biocontrol.
Transposable element insertion location bias and the dynamics of gene drive in mosquito populations
4280Rasgon, JLG, F., Insect Molecular Biology, 14:493-500. 2005-01-18 00:00:00.
Some vector-borne disease control strategies using transgenic mosquitoes require transgene spread to high frequency in populations. Transposable elements (TEs) are DNA sequences that replicate and transpose within the genomes of other organisms and may therefore be represented in the next generation in higher frequencies than predicted by Mendelian segregation. This over-representation has allowed some TEs to spread through natural populations. Transgenes incorporated within a TE sequence are expected to be driven into populations as long as there is a positive balance between fitness costs and over-representation. Models have been used to examine parameters that affect this balance but did not take into account biased insertion of TEs to linked sites in the genome. A simulation model was created to examine the impact of insertion bias on TE spread in mosquito populations. TEs that induce no fitness costs are predicted to increase in frequency over a wide range of parameter values but spread is slower for lower levels of transposition and non-local movement. If TEs are costly, high proportions of local movement can slow or halt spread. To function as a robust transgene drive mechanism a TE should replicate and transpose > 10%/insert/generation, induce < 1% fitness cost/insert, and move preferentially to unlinked sites in the genome.
Segregation distortion in hybrids between the Bogota and USA subspecies of Drosophila pseudoobscura
4279Orr, HAI, S., Genetics, 169:671-682. 2005-01-17 00:00:00.
We show that, contrary to claims in the literature, "sterile" males resulting from the cross of the Bogota and USA subspecies of Drosophila pseudoobscura are weakly fertile. Surprisingly, these hybrid males produce almost all daughters when crossed to females of any genotype (pure Bogota, pure USA, hybrid F-1). Several lines of evidence suggest that this sex ratio distortion is caused by sex chromosome segregation distortion in hybrid males. We genetically analyze this normally cryptic segregation distortion and show that it involves several regions of the Bogota X chromosome that show strong epistatic interactions with each other. We further show that segregation distortion is normally masked within the Bogota subspecies by amosomal suppressors. Our analysis shows that the genetic basis of hybrid segregation distortion is similar to that of hybrid male sterility between the same subspecies. Indeed the severity of segregation distortion is correlated with the severity of sterility among hybrids. We discuss the possibility that hybrid sterility in this paradigmatic case of incipient speciation is caused by segregation distortion.
Degeneration and domestication of a selfish gene in yeast: Molecular evolution versus site-directed mutagenesis
4278Koufopanou, VB, A., Molecular Biology and Evolution, 22:1535-1538. 2005-01-16 00:00:00.
VDE is a homing endonuclease gene in yeasts with an unusual evolutionary history including horizontal transmission, degeneration, and domestication into the mating-type switching locus HO. We investigate here the effects of these features on its molecular evolution. In addition, we correlate rates of evolution with results from site-directed mutagenesis studies. Functional elements have, lower rates of evolution than degenerate ones and higher conservation at functionally important sites. However, functionally important and unimportant sites are equally likely to have been involved in the evolution of new function during the domestication of VDE into HO. The domestication event also indicates that VDE has been lost in some species and that VDE has been present in yeasts for more than 50 Myr.
Meiotic drive at the Om locus in wild-derived inbred mouse strains
4277Kim, KT, S.; Howard, I. B.; Bell, T. A.; Doherty, H. E.; Ideraabdullah, F.; Detwiler, D. A.; De Villena, F. P. M., Biological Journal of the Linnean Society, 84:487-492. 2005-01-15 00:00:00.
Meiotic drive is an evolutionary force in which natural selection is uncoupled from organismal fitness. Recently, it has been proposed that meiotic drive and genetic drift represent major forces in the evolution of the mammalian karyotype. Meiotic drive involves two types of genetic elements, Responders and Distorters, the latter being required to induce transmission ratio distortion at the former. We have previously described the Om meiotic drive system in mouse chromosome 11. To investigate the natural history of this drive system we have characterized the alleles present at the distorter in wild-derived inbred strains. Our analysis of transmission of maternal alleles in both classical and wild-derived inbred strains indicated that driving alleles are found at high frequency in natural populations and that the existence of driving alleles predates the split between the Mus spicilegus and M. musculus lineages. (c) 2005 The Linnean Society of London.
Genetic linkage between a sexually selected trait and X chromosome meiotic drive
4276Johns, PMW, L. L.; Wilkinson, G. S., Proceedings of the Royal Society B-Biological Sciences, 272:2097-2103. 2005-01-14 00:00:00.
Previous studies on the stalk-eyed fly, Cyrtodiopsis dalmanni, have shown that males with long eye-stalks win contests and are preferred by females, and artificial selection on male relative eye span alters brood sex-ratios. Subsequent theory proposes that X-linked meiotic drive can catalyse the evolution of mate preferences when drive is linked to ornament genes. Here we test this prediction by mapping meiotic drive and quantitative trait loci (QTL) for eye span. To map QTL we genotyped 24 microsatellite loci using 1228 F2 flies from two crosses between lines selected for long or short eye span. The crosses differed by presence or absence of a drive X chromosome, X-D, in the parental male. Linkage analysis reveals that X-D dramatically reduces recombination between X and X-D chromosomes. In the X-D cross, half of the F2 males carried the drive haplotype, produced partially elongated spermatids and female-biased broods, and had shorter eye span. The largest QTL mapped 1.3 cM from drive on the X chromosome and explained 36% of the variation in male eye span while another QTL mapped to an autosomal region that suppresses drive. These results indicate that selfish genetic elements that distort the sex-ratio can influence the evolution of exaggerated traits.
Gene drive systems in mosquitoes: rules of the road
4275James, AA, Trends in Parasitology, 21:64-67. 2005-01-13 00:00:00.
Population replacement strategies for controlling transmission of mosquito-borne diseases call for the introgression of antipathogen effector genes into vector populations. It is anticipated that these genes, if present at high enough frequencies, will impede transmission of the target pathogens and result in reduced human morbidity and mortality. Recent laboratory successes in the development of virus- and protozoan-resistant mosquito strains make urgent research of gene drive systems capable of moving effector genes into wild populations. A systematic approach to developing safe and effective gene drive systems that includes defining the requirements of the system, identifying naturally occurring or synthetic genetic mechanisms for gene spread upon which drive systems can be based and the successful adaptation of a mechanism to a drive system, should mitigate concerns about using genetically engineered mosquitoes for disease control.
A novel meiotic drive locus almost completely distorts segregation in Mimulus (monkeyflower) hybrids
4274Fishman, LW, J. H., Genetics, 169:347-353. 2005-01-12 00:00:00.
We report the discovery, mapping, and characterization of a meiotic drive locus (D) exhibiting nearly 100% nonrandom transmission in hybrids between two species of yellow monkeyflowers, outcrossing Mimulus guttatus and selfing M. nasutus. Only 1% of F-2 hybrids were M. nasutus homozygotes at the marker most tightly linked to D. We used a set of reciprocal backcrosses to distinguish among male-specific, female-specific, and zygote-specific sources of transmission ratio distortion. Transmission was severely distorted only when the heterozygous F, acted as the female parent in crosses to either parental species, ruling out pollen competition and zygote mortality as potential sources of drive. After four generations of backcrossing to M. nasutus, nearly isogenic lines were still >90% heterozygous at markers linked to D, suggesting that heterozygosity at the drive locus alone is sufficient for nonrandom transmission. A lack of dramatic female fitness costs in these lines rules out alternatives involving ovule or seed mortality and points to a truly meiotic mechanism of drive. The strength and direction of drive in this system is consistent with population genetic theory of selfish element evolution under different mating systems. These results are the first empirical demonstration of the strong female-specific drive predicted by new models of selfish centromere turnover.
Sex chromosome meiotic drive in hybrid males of the common shrew (Sorex araneus)
4273Fedyk, SB, U.; Chetnicki, W., Folia Biologica-Krakow, 53:133-141. 2005-01-11 00:00:00.
Patterns of sex chromosome segregation in six homozygous males of the common Shrew (Sorex araneus LINNAEUS, 1758) belonging to two chromosomal races, as well as in 16 interracial hybrids were studied. I ascd on their karyotypes the hybrids can be subdivided into two groups: (a) complex heterozygotes, which form meiotic quadrivalents in chain and chain + ring configurations, and (b) complex heterozygotes, which Form meiotic pentavalents in chain configurations. Random 1 : 1) segregation of sex chromosomes was found ill homozygous as well as those he erozygous males which form meiotic complexes Of four chromosomes. However, in some, hybrids with meiotic pentavalents we observed a strong preferential segregation in favou of X chromosomes.
Intraparental gamete competition provides a selective advantage for the development of hybrid sterility via meiotic drive
Adams, CS, Evolution, 59:1229-1236. 2005-01-10 00:00:00.Hybrid sterility can have evolutionary significance and varies substantially by taxon, but few models attempt to predict or explain this variability. Hybrid sterility is commonly observed and develops early in isolation, at odds with straightforward models that predict it would develop slowly and rarely be seen. Meiotic drive might explain the rapid development of hybrid sterility, but drive is rarely observed, modifiers are expected to repress it, and no precise testable predictions are available. Here I develop population genetic models for the establishment of meiotic drive based on how it spreads by benefiting carrier gametes competing with noncarrier gametes from the same parent, or intraparental gamete competition. The resulting models predict that mciotic drive can often produce substantial hybrid sterility over time even in the presence of repressors, yet observable drive will be rare. They also make quantitative predictions of the degree of sterility based on observable parameters of reproductive ecology, including frequency of multiple mating, effective dispersal of offspring, and population size. Finally, they suggest explanations for the association of heterochromatin changes with speciation. Experimental evidence is discussed showing that drive alleles at least sometimes contribute to hybrid sterility.
TSETSE GENETICS: Contributions to Biology, Systematics, and Control of Tsetse Flies
26199R. H. Gooding and E. S. Krafsur, Annual Review of Entomology, 50:101-123. 2005-01-01 14:04:26.
Tsetse flies (Diptera: Glossinidae) constitute a small, ancient taxon of exclusively hematophagous insects that reproduce slowly and viviparously. Because tsetse flies are the only vectors of pathogenic African trypanosomes, they are a potent and constant threat to humans and livestock over much of sub-Saharan Africa. Despite their low fecundity, tsetse flies demonstrate great resilience, which makes population suppression expensive, transient, and beyond the capacities of private and public sectors to accomplish, except over small areas. Nevertheless, control measures that include genetic methods are under consideration at national and supranational levels. There is a pressing need for sufficient laboratory cultures of tsetse flies and financial support to carry out genetic research. Here we review tsetse genetics from organismal and population points of view and identify some research needs.
Evidence for extensive transmission distortion in the human genome
Zollner, SW, X. Q.; Hanchard, N. A.; Herbert, M. A.; Ober, C.; Pritchard, J. K., American Journal of Human Genetics, 74:62-72. 2004-01-21 00:00:00.It is a basic principle of genetics that each chromosome is transmitted from parent to offspring with a probability that is given by Mendel's laws. However, several known biological processes lead to skewed transmission probabilities among surviving offspring and, therefore, to excess genetic sharing among relatives. Examples include in utero selection against deleterious mutations, meiotic drive, and maternal-fetal incompatibility. Although these processes affect our basic understanding of inheritance, little is known about their overall impact in humans or other mammals. In this study, we examined genome screen data from 148 nuclear families, collected without reference to phenotype, to look for departures from Mendelian transmission proportions. Using single-point and multipoint linkage analysis, we detected a modest but significant genomewide shift towards excess genetic sharing among siblings (average sharing of 50.43% for the autosomes; P = .009). Our calculations indicate that many loci with skewed transmission are required to produce a genomewide shift of this magnitude. Since transmission distortion loci are subject to strong selection, this raises interesting questions about the evolutionary forces that keep them polymorphic. Finally, our results also have implications for mapping disease genes and for the genetics of fertility.
Evolution of autosomal suppression of the sex-ratio trait in Drosophila
4302Vaz, SCC, A. B., Genetics, 166:265-277. 2004-01-20 00:00:00.
The sex-ratio trait is the production of female-biased progenies due to X-linked meiotic drive in males of several Drosophila species. The driving X chromosome (called SR) is not fixed due to at least two stabilizing factors: natural selection (favoring ST, the nondriving standard X) and drive suppression by either Y-linked or autosomal genes. The evolution of autosomal suppression is explained by Fisher's principle, a mechanism of natural selectin that leads to equal proportion of males and females in a sexually reproducing population. In fact, sex-ratio expression is partially suppressed by autosomal genes in at least three Drosophila species. The population genetics of this system is not completely understood. In this article we develop a mathematical model for the evolution of autosomal suppressors of SR (sup alleles) and show that: (i) an autosomal suppressor cannot invade when SR is very deleterious in males (c < 1/3, where c is the fitness of SR/Y males); (ii) "SR/ST, sup/+" polymorphisms occur when SR is partially deleterious (similar to0.3 < c < 1); while (iii) SR neutrality (c = 1) results in sup fixation and thus in total abolishment of drive. So, surprisingly, as long as there is any selection against SR/Y males, neutral autosomal suppressors will not be fixed. In that case, when a polymorphic equilibrium exists, the average female proportion in SR/Y males' progeny is given approximately by (ac + 1 - a + roota(9) ( c + 1 )(2) + 1 - 4ac)/4ac, where a is the fitness of SR/ST females.
B chromosomes and genome size in flowering plants
4301Trivers, RB, A.; Palestis, B. G., Genome, 47:1-8. 2004-01-19 00:00:00.
B chromosomes are extra chromosomes found in some, but not all, individuals within a species, often maintained by giving themselves an advantage in transmission, i.e. they drive. Here we show that the presence of B chromosomes correlates to and varies strongly and positively with total genome size (excluding the Bs and corrected for ploidy) both at a global level and via a comparison of independent taxonomic contrasts. B chromosomes are largely absent from species with small genomes; however, species with large genomes are studied more frequently than species with small genomes and Bs are more likely to be reported in well-studied species. We controlled for intensity of study using logistic regression. This regression analysis also included effects of degree of outbreeding, which is positively associated with Bs and genome size, and chromosome number, which is negatively associated with Bs and genome size, as well as variable ploidy (more than one ploidy level in a species). Genome size, breeding system and chromosome number all contribute independently to the distribution of B chromosomes, while variable ploidy does not have a significant effect. The genome size correlates are consistent with reduced selection against extra DNA in species with large genomes and with increased generation of B sequences from large A genomes.
Wolbachia and cytoplasmic incompatibility in mosquitoes
4300Sinkins, SP, Insect Biochemistry and Molecular Biology, 34:723-729. 2004-01-18 00:00:00.
Wolbachia are maternally inherited bacteria that induce cytoplasmic incompatibility in mosquitoes, and are able to use these patterns of sterility to spread themselves through populations. For this reason they have been proposed as a gene drive system for mosquito genetic replacement, as well as for the reduction of population size or for modulating population age structure in order to reduce disease transmission. Here, recent progress in the study of mosquito Wolbachia is reviewed. We now have much more comprehensive estimates of the parameters that can affect the spread of Wolbachia through natural populations from low starting frequencies. and for waves of spread to be maintained in the face of partial barriers to gene flow. In Aedes albopictits these dynamics are extremely favourable, with very high maternal transmission fidelity and levels of incompatibility recorded. Correspondence between measurements taken in the lab and field is much better than in the Drosophila simulans model system. Important research goals are also discussed, including Wolbachia transformation, interspecific transfer and the elucidation of the mechanisms of incompatibility and rescue; all will be aided by a wealth of new Wolbachia genome information. (C) 2004 Elsevier Ltd. All rights reserved.
Evolution of divergent DNA recognition specificities in VDE homing endonucleases from two yeast species
4299Posey, KLK, V.; Burt, A.; Gimble, F. S., Nucleic Acids Research, 32:3947-3956. 2004-01-17 00:00:00.
Homing endonuclease genes (HEGs) are mobile DNA elements that are thought to confer no benefit to their host. They encode site-specific DNA endonucleases that perpetuate the element within a species population by homing and disseminate it between species by horizontal transfer. Several yeast species contain the VMA1 HEG that encodes the intein-associated VMA1-derived endonuclease (VIDE). The evolutionary state of VDEs from 12 species was assessed by assaying their endonuclease activities. Only two enzymes are active, PI-ZbaI from Zygosaccharomyces bailii and PI-ScaI from Saccharomyces cariocanus. PI-ZbaI cleaves the Z-bailii recognition sequence significantly faster than the Saccharomyces cerevisiae site, which differs at six nucleotide positions. A mutational analysis indicates that PI-ZbaI cleaves the S.cerevisiae substrate poorly due to the absence of a contact that is analogous to one made in PI-SceI between Gln-55 and nucleotides +9/+10. PI-ZbaI cleaves the Z.bailii substrate primarily due to a single base-pair substitution (A/T+5 --> T/A(+5)). Structural modeling of the PI-ZbaI/DNA complex suggests that Arg-331, which is absent in PI-SceI, contacts T/A(+5), and the reduced activity observed in a PI-ZbaI R331 A mutant provides evidence for this interaction. These data illustrate that homing endonucleases evolve altered specificity as they adapt to recognize alternative target sites.
Rapid suppression of drive for a parasitic B chromosome
4298Perfectti, FC, J. M.; Mesa, J. A.; Cabrero, J.; Bakkali, M.; Lopez-Leon, M. D.; Camacho, J. P. M., Cytogenetic and Genome Research, 106:338-343. 2004-01-16 00:00:00.
The persistence of parasitic B chromosomes in natural populations depends on both B ability to drive and host response to counteracting it. In the grasshopper Eyprepocnemis plorans, the B-24 chromosome is the most widespread B chromosome variant in the Torrox area ( Malaga, Spain). Its evolutionary success, replacing its ancestral neutralized B variant, B-2, was based on meiotic drive in females, as we showed in a sample caught in 1992. In females collected six years later, mean B-24 transmission ratio (k(B)) was 0.523, implying a very rapid decrease from the 0.696 observed in 1992. This shows that B-24 neutralization is running very fast and suggests that it might most likely be based on a single gene of major effect. Copyright (C) 2004 S. Karger AG, Basel.
The distribution of B chromosomes across species
4297Palestis, BGT, R.; Burt, A.; Jones, R. N., Cytogenetic and Genome Research, 106:151-158. 2004-01-15 00:00:00.
In this review we look at the broad picture of how B chromosomes are distributed across a wide range of species. We review recent studies of the factors associated with the presence of Bs across species, and provide new analyses with updated data and additional variables. The major obstacle facing comparative studies of B chromosome distribution is variation among species in the intensity of cytogenetic study. Because Bs are, by definition, not present in all individuals of a species, they may often be overlooked in species that are rarely studied. We give examples of corrections for differences in study effort, and show that after a variety of such corrections, strong correlations remain. Several major biological factors are associated with the presence of B chromosomes. Among flowering plants, Bs are more likely to occur in outcrossing than in inbred species, and their presence is also positively correlated with genome size and negatively with chromosome number. They are no more frequent in polyploids than in diploids, nor in species with multiple ploidies. Among mammals, Bs are more likely to occur in species with karyotypes consisting of mostly acrocentric chromosomes. We find no evidence for an association with chromosome number or genome size in mammals, although the sample for genome size is small. The associations with breeding system and acrocentric chromosomes were both predicted in advance, but those with genome size and chromosome number were discovered empirically and we can offer only tentative explanations for the very strong associations we have uncovered. Our understanding of why B chromosomes are present in some species and absent in others is still in its infancy, and we suggest several potential avenues for future research. Copyright (C) 2004 S. Karger AG, Basel.
B chromosomes are more frequent in mammals with acrocentric karyotypes: support for the theory of centromeric drive
4296Palestis, BGB, A.; Jones, R. N.; Trivers, R., Proceedings of the Royal Society B-Biological Sciences, 271:S22-S24. 2004-01-14 00:00:00.
The chromosomes of mammals tend to be either mostly acrocentric (having one long arm) or mostly bi-armed, with few species having intermediate karyotypes. The theory of centromeric drive suggests that this observation reflects a bias during female meiosis, favouring either more centromeres or fewer, and that the direction of this bias changes frequently over evolutionary time. B chromosomes are selfish genetic elements found in some individuals within some species. B chromosomes are often harmful, but persist because they drive (i.e. they are transmitted more frequently than expected). We predicted that species with mainly acrocentric chromosomes would be more likely to harbour B chromosomes than those with mainly bi-armed chromosomes, because female meiosis would favour more centromeres over fewer in species with one-armed chromosomes. Our results show that B chromosomes are indeed more common in species with acrocentric chromosomes, across all mammals, among rodents, among non-rodents and in a test of independent taxonomic contrasts. These results provide independent evidence supporting the theory of centromeric drive and also help to explain the distribution of selfish DNA across species. In addition, we demonstrate an association between the shape of the B chromosomes and the shape of the typical ('A') chromosomes.
Reinvestigation of an endogenous meiotic drive system in the mosquito, Aedes aegypti (Diptera : Culicidae)
4295Mori, AC, D. D.; Graham, D. H.; Severson, D. W., Journal of Medical Entomology, 41:1027-1033. 2004-01-13 00:00:00.
We have initiated efforts to determine the molecular basis for the M-D meiotic drive system in the mosquito, Aedes aegypti. The effect of the M-D gene is a highly male-biased sex ratio, but varies depending on the frequency and sensitivity of a susceptible responder m(s) allele. The M-D system has potential as a mechanism for driving trangenes for pathogen resistance into natural Ae. aegypti populations. Because all previously existing laboratory strains carrying the M-D gene have been lost, we have selected for a new strain, T37, that carries a strong driver. Matings between T37 males and drive-susceptible in m(s) females result in progeny with highly biased sex ratios, wherein only approximate to14.7% females are produced. We discuss the potential for identifying M-D candidate genes based on comparisons with the well-described Drosophila melanogaster segregation distorter (SD) meiotic drive system and considerations for release of transgenic Ae. aegypti into natural populations where M-D and insensitive m(i) alleles are likely segregating.
Mapping of paternal-sex-ratio deletion chromosomes localizes multiple regions involved in expression and transmission
4294McAllister, BFB, L. W.; Werren, J. H., Heredity, 92:5-13. 2004-01-12 00:00:00.
The paternal-sex-ratio (PSR) chromosome in the parasitic wasp Nasonia vitripennis is a submetacentric supernumerary (B chromosome). Males transmit PSR, but after fertilization it causes the loss of the paternal autosomes. Paternal genome loss caused by PSR results in the conversion of a female (diploid) zygote into a male (haploid) under haplodiploid sex determination. In this study, site-specific markers were developed to assay deletion derivatives of PSR. Both polymerase chain reaction and Southern hybridization were used to detect the presence/absence of 16 single-site markers on a set of 20 functional and nine nonfunctional deletion chromosomes. Based on the pattern of marker loss on the deletion chromosomes, the basic organization of PSR was revealed. Two sets of markers were deleted independently, apparently representing the two arms of the submetacentric chromosome. The presence or absence of specific regions was examined in relation to phenotypic characteristics of the deletion chromosomes; ability to cause paternal genome loss, and stability in mitotic cell divisions. Rather than identifying a single region on PSR as being responsible for PSR function, the results suggest that the retention of one of two chromosomal regions is sufficient for causing paternal genome loss. Furthermore, a region was identified that is tightly correlated with mitotic stability, as measured from chromosomal transmission rates. Functional chromosomes with short-arm deletions had high (similar to100%) transmission rates, whereas functional chromosomes with long-arm deletions had low (similar to85%) transmission rates.
B chromosomes in Sternorrhyncha (Hemiptera, Insecta)
4293Maryanska-Nadachowska, A, Cytogenetic and Genome Research, 106:210-214. 2004-01-11 00:00:00.
In the hemipteroid insects of the suborder Sternorrhyncha, B chromosomes are relatively common in comparison with other suborders of Hemiptera. However, the occurrence of supernumerary chromosomes is restricted, in most cases, to several genera or closely related species. At least in some species of Psylloidea with the XY sex determination system, a mitotically stable B chromosome integrated into an achiasmatic segregation system with the X, and became fixed as a Y chromosome. In some Aphidoidea with a multiple X system of sex determination, B chromosomes appear to be in fact non-functional X chromosomes. Supernumerary chromosomes thus probably play an important role in the evolution of sex determination systems in Sternorrhyncha. Copyright (C) 2004 S. Karger AG, Basel.
Exploring the public understanding of basic genetic concepts
Lanie, ADJ, Toby Epstein; Sheldon, Jane P.; Kardia, Sharon L. R.; Anderson, Elizabeth S.; Feldbaum, Merle; Petty, Elizabeth M., Journal of Genetic Counseling, 13:305-320. 2004-01-10 00:00:00.It is predicted that the rapid acquisition of new genetic knowledge and related applications during the next decade will have significant implications for virtually all members of society. Currently, most people get exposed to information about genes and genetics only through stories publicized in the media. We sought to understand how individuals in the general population used and understood the concepts of "genetics" and "genes." During in-depth one-on-one telephone interviews with adults in the United States, we asked questions exploring their basic understanding of these terms, as well as their belief as to the location of genes in the human body. A wide range of responses was received. Despite conversational familiarity with genetic terminology, many noted frustration or were hesitant when trying to answer these questions. In addition, some responses reflected a lack of understanding about basic genetic science that may have significant implications for broader public education measures in genetic literacy, genetic counseling, public health practices, and even routine health care.
Meiotic drive and sex chromosome cycling
4291Hall, DW, Evolution, 58:925-931. 2004-01-09 00:00:00.
Sex-linked meiotic drive is found in a broad variety of taxa, including insects, birds, and mammals. In populations of some species, we see four types of sex chromosomes segregating: normal and driving X chromosomes and susceptible and resistant Y chromosomes. A theoretical analysis shows that a stable four-chromosome equilibria is a more common outcome in these systems than previously recognized. Cycling of sex chromosome frequencies and associated changes in the sex ratio are other predicted outcomes. The absence of cycling in nature may be due to migration among populations.
Identification of quantitative trait loci affecting sex determination in the eastern treehole mosquito (Ochlerotatus triseriatus)
4290Graham, DHH, J. L.; Black, W. C., Journal of Heredity, 95:35-45. 2004-01-08 00:00:00.
Laboratory colonies of the eastern treehole mosquito (Ochlerotatus triseriatus (Say)) exhibit a consistent female-biased sex ratio. This is unusual among mosquito species, in which heritable sex ratio distortion is usually male biased and mediated by meiotic drive. Quantitative trait loci (QTL) affecting sex were mapped in an F-1 intercross to better understand the genetics underlying this female bias. In P-1 and F-1 parents and in 146 F-2 individuals with a female-biased sex ratio (106 females:40 males), regions of seven cDNA loci were analyzed with single-strand conformation polymorphism (SSCP) analysis to identify and orient linkage groups. Genotypes were also scored at 73 random amplified polymorphic DNA (RAPD)-SSCP loci. In addition to the sex locus, at least four QTL affecting sex determination were detected with interval mapping on linkage groups I and II. Alleles at the sex locus cumulatively accounted for approximately 61-77% of the genetic variance in sex. Alleles at QTL adjacent to the sex locus and at a QTL on the opposite end of linkage group I increased the proportion of females, but alleles at a QTL on linkage group I and a second QTL on linkage group II increased the proportion of males. The female-biased sex ratio observed in laboratory colonies of O. triseriatus is most easily explained by the existence of multiple female biased distorter loci, as have been observed in other Diptera.
Sperm survival in female stalk-eyed flies depends on seminal fluid and meiotic drive
4289Fry, CLW, G. S., Evolution, 58:1622-1626. 2004-01-07 00:00:00.
Sperm competition is common in many insect species; however, the mechanisms underlying differences in sperm precedence are not well understood. In the stalk-eyed fly, Cyrtodiopsis whitei (Diptera, Diopsidae), sperm precedence is influenced by the presence of sex chromosome meiotic drive. When drive-carrying males compete with non-driving males for fertilizations within a female, the number of progeny sired by drive males is significantly fewer than predicted by sperm mixing alone. Thus, drive males apparently suffer not only a reduction in the number of viable sperm produced, but also a reduction in sperm competitive ability. In this study, we manipulated the amount and source of seminal fluid and sperm received by females by interrupting copulations before sperm, but after seminal fluid, was transferred. We find that seminal fluid from another male influences the number of progeny sired by a drive-carrying male when both males mate with the same female. Sperm viability staining reveals that sperm from drive males are incapacitated by seminal fluid from other males within the female reproductive tract. These results suggest that multiple mating by females enables seminal fluid products to interact differentially with sperm and may reduce the transmission advantage of the drive chromosome.
To what extent do different types of sex ratio distorters interfere?
4288Engelstadter, JM, H.; Hurst, G. D. D., Evolution, 58:2382-2386. 2004-01-06 00:00:00.
Within the Diptera, two different selfish genetic elements are known to cause the production of female-biased sex ratios: maternally inherited bacteria that kill male zygotes (male-killers), and X chromosomes causing the degeneration of Y-bearing sperm in males (meiotic drive). We here develop a mathematical model for the dynamics of these two sex-ratio distorters where they co-occur. We show that X chromosome meiotic drive elements can be expected to substantially lower the equilibrium frequency of male-killers and can even lead to their extinction. Conversely, male-killers can also decrease the equilibrium frequency of X drivers and cause their extinction. Thus, we predict that there will be some complementarity in the incidence of X chromosome meiotic drive and male-killing in natural populations, with a lower than expected number of species bearing both elements.
Persistence of an extreme sex-ratio bias in a natural population
4287Dyson, EAH, G. D. D., Proceedings of the National Academy of Sciences of the United States of America, 101:6520-6523. 2004-01-05 00:00:00.
The sex ratio is a key parameter in the evolution and ecology of a species. Selfish genetic elements that bias the sex ratio of affected individuals are well known and characterized, but their effect on populations has been considered limited, because either the element does not achieve high prevalence or the host rapidly evolves resistance to the distorting element, reducing its prevalence. We tested whether the host necessarily prevails by using a butterfly system where records from the early part of the 20th century reported extreme sex-ratio bias in nature. We reexamined this population and found the bias was present today, 400 generations after the original record, with a population sex ratio of 100 females per male. The sex-ratio bias was associated with the presence of a heritable male-killing Wolbachia infection in 99% of adult females, against which the host butterfly has failed to evolve resistance. The resultant dearth of males causes an average 57% reduction in the reproductive output of adult females. Persistence of the population despite the very high frequency of the sex-ratio distorter appears to be associated with the ability of males to mate >50 times in their life combined with a high intrinsic rate of increase of the species.
Homing endonuclease genes: the rise and fall and rise again of a selfish element
4286Burt, AK, V., Current Opinion in Genetics & Development, 14:609-615. 2004-01-04 00:00:00.
Homing endonuclease genes (HEGs) are selfish genetic elements that spread by first cleaving chromosomes that do not contain them and then getting copied across to the broken chromosome as a byproduct of the repair process. The success of this strategy will depend on the opportunities for homing - in other words, the frequency with which HEG(+) and HEG(-) chromosomes come into contact - which varies widely among host taxa. HEGs are also unusual in that the selection pressure for endonuclease function disappears if they become fixed in a population, which makes them susceptible to degeneration and imposes a need for regular horizontal transmission between species. HEGs will be selected to reduce the harm done to the host organism, and this is expected to influence the evolution of their sequence specificity and maturase functions. HEGs may also be domesticated by their hosts, and are currently being put to human uses.
Inverted meiosis and meiotic drive in mealybugs
4285Bongiorni, SF, P.; Pippoletti, D.; Prantera, G., Chromosoma, 112:331-341. 2004-01-03 00:00:00.
In the males of lecanoid coccids, or mealybugs, an entire, paternally derived, haploid chromosome set becomes heterochromatic after the seventh embryonic mitotic cycle. In females, both haploid sets are euchromatic throughout the life cycle. In mealybugs, as in all homopteran species, chromosomes are holocentric. Holocentric chromosomes are characterized by the lack of a localized centromere and consequently of a localized kinetic activity. In monocentric species, sister chromatid cohesion and monopolar attachment play a pivotal role in regulating chromosome behavior during the two meiotic divisions. Both these processes rely upon the presence of a single, localized centromere and as such cannot be properly executed by holocentric chromosomes. Here we furnish further evidence that meiosis is inverted in both sexes of mealybugs and we suggest how this might represent an adaptation to chromosome holocentrism. Moreover, we reveal that at the second meiotic division in males a monopolar spindle is formed, to which only euchromatic chromosomes become attached. By this mechanism the paternally derived, heterochromatic, haploid chromosome set strictly segregates from the euchromatic one, and it is then excluded from the genetic continuum as a result of meiotic drive.
The B chromosome polymorphism of the grasshopper Eyprepocnemis plorans in North Africa. IV. Transmission of rare B chromosome variants
4284Bakkali, MC, J. P. M., Cytogenetic and Genome Research, 106:332-337. 2004-01-02 00:00:00.
In addition to the principal B chromosome (B-1) in Moroccan populations of the grasshopper Eyprepocnemis plorans, nine B chromosome variants appeared at low frequency. The transmission of five of these rare B chromosome variants through females was analysed in three natural populations. Sixteen controlled crosses provided useful information on the transmission of B-M2, B-M6 and B-M7 in Smir, B-M3 and B-M6 in SO. DE. A. (Societe de Developpement Agricole lands near Ksar-el-Kebir city), and B-M2 and BM10 in Mechra, all located in Morocco. Since six female parents carried two different B variants, a total of 22 progeny analyses could be studied. Intraindividual variation in B transmission rate (k(B)) was observed among the successive egg pods in 26.7% of the females, but this variation did not show a consistent temporal pattern. Only the B-M2 and B-M6 variants in Smir showed net drive, although variation was high among crosses, especially for B-M2. These two variants are thus good candidates for future regenerations ( the replacement of a neutralized B, B-1 in this case, by a new driving variant, B-M2 or B-M6) in Smir, the northern population where the B polymorphism is presumably older. The analysis of all crosses performed in the three populations, including those reported previously for the analysis of B-1 transmission, showed that the largest variance in k(B) among crosses stands at the individual level, and not at population or type of B levels. The implications of these findings for the occurrence of possible regeneration processes in Moroccan populations are discussed. Copyright (C) 2004 S. Karger AG, Basel.
Analysis of two additional loci in Neurospora crassa related to Spore killer-2
4319Turner, BC, Fungal Genetics and Biology, 39:142-150. 2003-01-17 00:00:00.
Two new loci found in one strain of Neurospora crassa (P2604) collected in Malaya are related to the meiotic drive system Spore killer Sk-2. Sk-2 was found in Neurospora intermedia and introgressed into N. crassa. P2604 showed high resistance to killing when crossed to Sk-2. This resistance was found to be linked to, but not allelic to, resistance locus r(Sk-2) on LGIIIL. Analysis showed that the high resistance phenotype of P2604 requires resistance alleles at two different loci on LGIIIR. Strains carrying a resistance allele at only the proximal or the distal locus, respectively, were obtained and intercrossed. Highly resistant strains were obtained by rejoining the two genes. The proximal locus alone confers a low level of resistance. This locus was named pr(Sk-2) for partial resistance to Sk-2. The distal locus was named mod(pr) because its only known phenotype is to modify pr(Sk-2). (C) 2003 Elsevier Science (USA). All rights reserved.
Common features of segregation distortion in plants and animals
4318Taylor, DRI, P. K., Genetica, 117:27-35. 2003-01-16 00:00:00.
Segregation distortion is increasingly recognized as a potentially powerful evolutionary force. This runs counter to the perception that non-Mendelian genes are rare genetic curiosities, a view that seems to be supported by the near ubiquity of the Mendelian system of inheritance. There are several reasons why segregation distortion may be more important than is evidenced by known empirical examples. One possibility is that the types of segregation distorters we have found are only a subset of a broader range of non-Mendelian systems, many of which go undetected. In this paper, we review what is known about the sex-linked meiotic drive system in the plant, Silene latifolia, and present some data on the mechanism of segregation distortion. We outline the general features that segregation distorters in plants and animals have in common. In some cases, such as the paucity of systems that directly alter meiotic segregation, there are likely to be inherent constraints on the range of systems that can possibly occur. Other generalities, however, support the notion that many forms of meiotic drive are possible, and that the known examples of segregation distortion are likely to be only subset of those that can possibly occur. Non-Mendelian genes may therefore have greater evolutionary importance than their current abundance in nature would suggest.
Genetic dissection of hybrid incompatibilities between Drosophila simulans and D-mauritiana. III. Heterogeneous accumulation of hybrid incompatibilities, degree of dominance, and implications for Haldane’s rule
4317Tao, YH, D. L., Evolution, 57:2580-2598. 2003-01-15 00:00:00.
The genetic basis of Haldane's rule was investigated through estimating the accumulation of hybrid incompatibilities between Drosophila simulans and D. mauritiana by means of introgression. The accumulation of hybrid male sterility (HMS) is at least 10 times greater than that of hybrid female sterility (HFS) or hybrid lethality (HL). The degree of dominance for HMS and HL in a pure D. simulans background is estimated as 0.23-0.29 and 0.33-0.39, respectively; that for HL in an F-1 background is unlikely to be very small. Evidence obtained here was used to test the Turelli-Orr model of Haldane's rule. Composite causes, especially, faster-male evolution and recessive hybrid incompatibilities, underlie Haldane's rule in heterogametic male taxa such as Drosophila (XY male and XX female). However, if faster-male evolution is driven by sexual selection, it contradicts Haldane's rule for sterility in heterogametic-female taxa such as Lepidoptera (ZW female and ZZ male). The hypothesis of a faster-heterogametic-sex evolution seems to fit the current data best. This hypothesis states that gametogenesis in the heterogametic sex, instead of in males per se, evolves much faster than in the homogametic sex, in part because of sex-ratio selection. This hypothesis not only explains Haldane's rule in a simple way, but also suggests that genomic conflicts play a major role in evolution and speciation.
Meiotic drive – Bickering genes shape evolution – Not all genes follow the rules of inheritance; now researchers are discovering how organisms adapt to the troublemakers
4316Pennisi, E, Science, 301:1837-1839. 2003-01-14 00:00:00.
Reproduction is supposed to be an equal opportunity event. Consider humans: In developing sperm, the sex chromosomes sort 50:50 such that half the sperm carry the male-defining Y chromosome and the rest sport an X. Only the randomness of fertilization leads to families of nine girls and no boys, for example. The same supposedly holds true for the rest of the genome. But in humans, flies, mice, and perhaps many other organisms, guerrilla warfare within the genome sometimes pits one element against another. This often takes on the appearance of a battle between the sexes, but it is really a fight between genes. In this struggle, typically one or more of the X chromosome’s genes strike out against the Y’s genes. Genes on other chromosomes also can get caught up in this struggle, causing an escalating arms race.
The aging effect in the segregation distorter system of Drosophila melanogaster
4315Oh, SCN, J. G., Korean Journal of Genetics, 25:237-242. 2003-01-13 00:00:00.
The SD/SD+ heterozygous male of Drosophila melanogaster transmits the SD second chromosome to its progeny in excess of the Mendelian frequency of 0.5. The k value is defined as the frequency of the SD chromosome recovered among progeny from such a male. This value has been shown to be affected by the age of the male parent: it tends to decrease with increasing age of the parental male, and this aging effect is heritable. The present study indicates that there is a genotypic condition in which the effect of male age is to increase the k value, and this increase is heritable. Thus, a heritable aging effect can occur in both increasing and decreasing the k values, depending upon the genotypes.
Transmission ratio distortion in mice
4314Lyon, MF, Annual Review of Genetics, 37:393-408. 2003-01-12 00:00:00.
The most studied example of transmission ratio distortion (TRD) in mice is that of the t-complex. This is a variant-region of Chromosome 17 which exists as a polymorphism in wild mice. Males heterozygous for a t-haplotype and a normal Chr 17 transmit-the t haplotype to >50% of their young, up to 99%.- Homozygous males are-sterile. The TRD produced by-the t-complex, is due to the action of three or more distorter genes (Tcd) on a responder. gene (Tcr). t-Haplotypes are maintained intact by crossover suppression induced by four neighboring inversions, the Tcd and by Tcr loci lying in different inversions. Sperm formation is normal in t/t males, but sperm function is impaired through gross defects in sperm motility. The responder gene has been identified as a fusion gene formed from a sperm motility kinase and a ribosomal S6 kinase. Three candidate distorter genes have also been identified as genes coding for dynein chains, and thus possibly involved in sperm flagellar function.
Closing the (Ran)GAP on segregation distortion in Drosophila
4313Kusano, AS, C.; Chan, H. Y. E.; Ganetzky, B., Bioessays, 25:108-115. 2003-01-11 00:00:00.
Segregation Distorter (SD) is a meiotic drive system in Drosophila that causes preferential transmission of the SD chromosome from SD/SD+ males owing to induced dysfunction of SD+ spermatids. Since its discovery in 1956, SD and its mode of action have baffled biologists. Recently, substantial progress has been made in elucidating this puzzle. Sd, the primary gene responsible for distortion encodes a mutant RanGAP, a key protein in the Ran signaling pathway required for nuclear transport and other nuclear functions. The mutant protein is enzymatically active but mislocalized to nuclei, which apparently disrupts Ran signaling by reducing intranuclear Ran-GTP levels. Some evidence suggests that a defect in nuclear transport may be the main cause of sperm dysfunction. Although important questions remain, the basic mechanism of distortion is now understood sufficiently well that specific hypotheses can be formulated and tested. This previously mysterious genetic system may now offer unique insights into novel aspects of regulation by Ran. (C) 2003 Wiley Periodicals, Inc.
B chromosomes in plants: escapees from the A chromosome genome?
4312Jones, NH, A., Trends in Plant Science, 8:417-423. 2003-01-10 00:00:00.
B chromosomes are dispensable elements that do not recombine with the A chromosomes of the regular complement and that follow their own evolutionary track. In some cases, they are known to be nuclear parasites with autonomous modes of inheritance, exploiting 'drive' to ensure their survival in populations. Their I selfishness' brings them into conflict with their host nuclear genome and generates a host-parasite relationship, with anti-B-chromosome genes working to ameliorate the worst of their excesses in depriving their hosts of genetic resources. Molecular studies are homing in on their sequence organization to give us an insight into the origin and evolution of these enigmatic chromosomes, which are, with rare exceptions, without active genes.
Responder (Rsp) alleles in the Segregation Distorter (SD) system of meiotic drive in Drosophila may represent a complex family of satellite repeat sequences
4311Houtchens, KL, T. W., Genetica, 117:291-302. 2003-01-09 00:00:00.
In D. melanogaster males carrying Segregation Distorter (SD) second chromosomes, sperm receiving sensitive alleles of the Responder (Rsp) locus are subject to high rates of dysfunction. The Rsp region is located in 2R immediately adjacent to the centromere in heterochromatic band 39, and covers roughly 600 kb of material, of which approximately 85 kb is comprised of several hundred copies of a 240-bp satellite DNA sequence. Cytological observations as well as molecular analysis of rearrangements which bisect h39 indicate that sensitivity of the Rsp target to SD action is also subdivisible, and sensitivities of the component pieces appear to be correlated with copy number of the 240 bp repeat. In an attempt to examine possible higher order sequence structure for these blocks, PCR using single primers derived from a canonical repeat was used to identify potential reversals of direction of tandem arrays; that is, head-to-head or tail-to-tail junctions. Surprisingly, for two different Rsp alleles, only a single such reversal product for each was identified, differing in size and sequence between alleles. Sequencing of PCR products identified diverged copies of the canonical repeats that would not have been found using the levels of DNA stringency employed in earlier studies. Examination of Southern digests and slot-blots for DNA quantification indicates that adding the estimated numbers of such diverged copies to the canonical repeat copies discovered earlier is potentially sufficient to account for the entire 600 kb Rsp region. This adds strength to the hypothesis that this extended family of repeats is in fact the target of SD-mediated sperm dysfunction. Implications of these results for understanding the evolution of repetitive DNA are also discussed.
General principles for risk assessment of living modified organisms: Lessons from chemical risk assessment
4310Hill, RAS, C., Environ. Biosafety Res, 2:81-88. 2003-01-08 00:00:00.
Modern biotechnology has led to the development and use of Living Modified Organisms (LMOs) for agriculture and other purposes. Regulators at the national level are increasingly depending on risk assessment as a tool for assessing potential adverse effects of LMOs on the environment and human health. In addition, the Cartagena Protocol on Biosafety, an international agreement expected to enter into force in the near future, requires risk assessment as the basis for decision-making regarding import of some LMOs. While LMO risk assessment is relatively new, there are other risk assessment disciplines which have developed over longer time periods. The field of assessment of the environmental and human health risks of chemicals is particularly well developed, and is similar in application to LMO risk assessment. This paper aims to draw lessons for LMO risk assessment from the vast experience with chemical risk assessment. Seven general principles are outlined which should serve as a useful checklist to guide assessments of risks posed by LMOs.
Four loci on abnormal chromosome 10 contribute to meiotic drive in maize
4309Hiatt, END, R. K., Genetics, 164:699-709. 2003-01-07 00:00:00.
We provide a genetic analysis of the meiotic drive system on maize abnormal chromosome 10 (Ab10) that causes preferential segregation of specific chromosomal regions to the reproductive megaspore. The data indicate that at least four chromosomal regions contribute to meiotic drive, each providing distinct functions that can be differentiated from each other genetically and/or phenotypically. Previous reports established that meiotic drive requires neocentromere activity at specific tandem repeat arrays (knobs) and that two regions on Ab10 are involved in trans-activating neocentromeres. Here we confirm and extend data suggesting that only one of the neocentromere-activating regions is sufficient to move many knobs. We also confirm the localization of a locus/loci on Ab10, thought to be a prerequisite for meiotic drive, which promotes recombination in structural heterozygotes. In addition, we identified two new and independent functions required for meiotic drive. One was identified through the characterization of a deletion derivative of Ab10 [Df(L)] and another as a newly identified meiotic drive mutation (suppressor Of meiotic drive 3). In the absence of either function, meiotic drive is abolished but neocentromere activity and the recombination effect typical of Ab10 are unaffected. These results demonstrate that neocentromere activity and increased recombination are not the only events required for meiotic drive.
The meiotic drive system on maize abnormal chromosome 10 contains few essential genes
4308Hiatt, END, R. K., Genetica, 117:67-76. 2003-01-06 00:00:00.
In maize, a distal portion of abnormal chromosome 10 (Ab10) causes the meiotic drive of itself as well as many unlinked heterochromatic regions known as knobs. The Ab10 drive system, which encodes trans- as well as cis-acting components, occupies a large region of chromosome 10L equivalent to similar to3% of the genome. Here we describe five new structural mutations of Ab10 (five deletions and a duplication) that arose from a screen for meiotic drive mutants. The high frequency of breakage events, detected both genetically and cytologically, suggest that the chromosome may be especially unstable. Very large deletions within the drive system are female-transmissible and plants homozygous for deficiencies lacking much of this interval can be grown to maturity. The data suggest that few genes required for normal growth and development lie within the portion of Ab10 responsible for meiotic drive. These and other published data suggest that meiotic drive systems tend to evolve in gene-sparse or otherwise information-poor regions of the genome where they are less likely to negatively affect individual fitness.
Sexual transmission of the Het-s prion leads to meiotic drive in Poldospora anserina
4307Dalstra, HJPS, K.; Debets, A. J. M.; Saupe, S. J.; Hoekstra, R. F., Proceedings of the National Academy of Sciences of the United States of America, 100:6616-6621. 2003-01-05 00:00:00.
In the filamentous fungus Podospora anserina, two phenomena are associated with polymorphism at the het-s locus, vegetative incompatibility and ascospore abortion. Two het-s alleles occur naturally, het-s and het-S. The het-s encoded protein is a prion propagating as a self-perpetuating amyloid aggregate. When prion-infected [Het-s] hyphae fuse with [Het-S] hyphae, the resulting heterokaryotic cells necrotize. [Het-s] and [Het-S] strains are sexually compatible. When, however, a female [Het-s] crosses with [Het-S], a significant percentage of het-S spores abort, in a way similar to spore killing in Neurospora and Podospora. We report here that sexual transmission of the [Het-s] prion after nonisogamous mating in the reproductive cycle of Podospora is responsible for the killing of het-S spores. Progeny of crosses between isogenic strains with distinct wild-type or introduced, ectopic het-s/S alleles were cytologically and genetically analyzed. The effect of het-s/S overexpression, ectopic het-s/S expression, absence of het-s expression, loss of [Het-s] prion infection, and the distribution patterns of HET-s/S-GFP proteins were categorized during meiosis and ascospore formation. This study unveiled a het-S spore-killing system that is governed by dosage of and interaction between the [Het-s] prion and the HET-S protein. Due to this property of the [Het-s] prion, the het-s allele acts as a meiotic drive element favoring maintenance of the prion-forming allele in natural populations.
Site-specific selfish genes as tools for the control and genetic engineering of natural populations
4306Burt, A, Proceedings of the Royal Society B-Biological Sciences, 270:921-928. 2003-01-04 00:00:00.
Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.
Marcus Rhoades, preferential segregation and meiotic drive
4305Birchler, JAD, R. K.; Doebley, J. F., Genetics, 164:835-841. 2003-01-03 00:00:00.
LONG before microarray biologists coined and promoted the term “discovery science,” maize geneticists were avid practitioners of this mode of investigation. In fact, one might say that for a number of years, the field of maize genetics basically operated as discovery science. Many have speculated about why maize remains a model organism for genetic analysis, given its long life cycle relative to other species. It has many virtues, sometimes little understood or appreciated by outsiders, but the maize geneticist’s style of science devoted to discovery and an unusually strong commitment to cooperation probably contributes to this trend. One of the great practitioners of this style of science was Marcus Rhoades (Figure 1), who often advised beginning graduate students: “Just get in the lab and start to work; you can’t help but find something.” “What are the facts?” was his common refrain to model building and theorizing. Along with his penchant for discovery was a dogged experimentalist attack to explore the parameters and dimensions of a new finding.
Overlapping deletions spanning the proximal two-thirds of the mouse t complex
Bergstrom, DEB, R. A.; Munroe, R. J.; Lee, B. K.; Browning, V. L.; You, Y.; Eicher, E. M.; Schimenti, J. C., Mammalian Genome, 14:817-829. 2003-01-02 00:00:00.Chromosome deletion complexes in model organisms serve as valuable genetic tools for the functional and physical annotation of complex genomes. Among their many roles, deletions can serve as mapping tools for simple or quantitative trait loci (QTLs), genetic reagents for regional mutagenesis experiments, and, in the case of mice, models of human contiguous gene deletion syndromes. Deletions also are uniquely suited for identifying regions of the genome containing haploinsufficient or imprinted loci. Here we describe the creation of new deletions at the proximal end of mouse Chromosome (Chr) 17 by using the technique of ES cell irradiation and the extensive molecular characterization of these and previously isolated deletions that, in total, cover much of the mouse t complex. The deletions are arranged in five overlapping complexes that collectively span about 25 Mbp. Furthermore, we have integrated each of the deletion complexes with physical data from public and private mouse genome sequences, and our own genetic data, to resolve some discrepancies. These deletions will be useful for characterizing several phenomena related to the t complex and t haplotypes, including transmission ratio distortion, male infertility, and the collection of t haplotype embryonic lethal mutations. The deletions will also be useful for mapping other loci of interest on proximal Chr 17, including T-associated sex reversal (Tas) and head-tilt (het). The new deletions have thus far been used to localize the recently identified t haplolethal (Thl1) locus to an approximately 1.3-Mbp interval.
Adaptation for horizontal transfer in a homing endonuclease
4323Koufopanou, VG, M. R.; Burt, A., Molecular Biology and Evolution, 19:239-246. 2002-01-21 00:00:00.
Selfish genes of no function other than self-propagation are susceptible to degeneration if they become fixed in a population. and regular transfer to new species may be the only means for their long-term persistence. To test this idea we surveyed 24 species of yeast for VDE, a nuclear. intein-associated homing endonuclease gene (HEG) originally discovered in Saccharomyces cerevisiae. Phylogenetic analyses show that horizontal transmission has been a regular occurrence in its evolutionary history. Moreover, VDE appears to be specifically adapted for horizontal transmission. Its 31-bp recognition sequence is an unusually well-conserved region in an unusually well-conserved gene. In addition, the nine nucleotide sites most critical for homing are also unusually well conserved. Such adaptation for horizontal transmission presumably arose as a consequence of selection, both among HEGs at different locations in the genome and among variant,,, at the same location. The frequency of horizontal transmission must therefore be a key feature constraining the distribution and abundance of these genes.
Reciprocal crossover asymmetry and meiotic drive in a human recombination hot spot
4322Jeffreys, AJN, R., Nature Genetics, 31:267-271. 2002-01-20 00:00:00.
Human DNA diversity arises ultimately from germline mutation that creates new haplotypes that can be reshuffled by meiotic recombination. Reciprocal crossover generates recombinant haplotypes but should not influence the frequencies of alleles in a population. We demonstrate crossover asymmetry at a recombination hot spot in the major histocompatibility complex(1), whereby reciprocal exchanges in sperm map to different locations in the hot spot. We identify a single-nucleotide polymorphism at the center of the hot spot and show that, when heterozygous, it seems sufficient to cause this asymmetry, apparently by influencing the efficiency of highly localized crossover initiation. As a consequence, crossovers in heterozygotes are accompanied by biased gene conversion, most likely occurring by gap repair(2), that can also affect nearby polymorphisms through repair of an extended gap. The result is substantial over-transmission of the recombination-suppressing allele and neighboring markers to crossover products. Computer simulations show that this meiotic drive, although weak at the population level, is sufficient to favor eventual fixation of the recombination-suppressing variant. These findings provide an explanation for the relatively uniform widths of human crossover hot spots and suggest that hot spots may be generally prone to extinction by meiotic drive(3).
X chromosome effect on maternal recombination and meiotic drive in the mouse
4321de la Casa-Esperon, EL-O, J. C.; de Villena, F. P. M.; Briscoe, T. L.; Malette, J. M.; Vaughan, J. E.; Morgan, K.; Sapienza, C., Genetics, 161:1651-1659. 2002-01-19 00:00:00.
We observed that maternal meiotic drive favoring the inheritance of DDK alleles at the Om locus on mouse chromosome 11 was correlated with the X chromosome inactivation phenotype of (C57BL/6Pgk1(a) X DDK)F-1 mothers. The basis for this unexpected observation appears to lie in the well-documented effect of recombination on meiotic drive that results from nonrandom segregation of chromosomes. Our analysis of genome-wide levels of meiotic recombination in females that vary in their X-inactivation phenotype indicates that an allelic difference at an X-linked locus is responsible for modulating levels of recombination in oocytes.
Does Stellate cause meiotic drive in Drosophila melanogaster?
4320Belloni, MT, P.; Bozzetti, M. P.; Palumbo, G.; Robbins, L. G., Genetics, 161:1551-1559. 2002-01-18 00:00:00.
Drosophila melanogaster males deficient for the crystal (cry) locus of the Y chromosome that carry between 15 and 60 copies of the X-linked Stellate (Ste) gene are semisterile, have elevated levels of nondisjunction, produce distorted sperm genotype ratios (meiotic drive), and evince hyperactive transcription of Ste in the testes. Ste seems to be the active element in this system, and it has been proposed that the ancestral Ste gene was "selfish" and increased in frequency because it caused meiotic drive. This hypothetical evolutionary history is based on the idea that Ste overexpression, and not the lack of cry, causes the meiotic drive of cry(-) males. To test whether this is true, we have constructed a Ste-deleted X chromosome and examined the phenotype of Ste(-)/cry(-) males. If hyperactivity of Ste were necessary for the transmission defects seen in cry- males, cry males completely deficient for.Ste would be normal. Although it is impossible to construct a completely Ste(-) genotype, we find that Ste(-)/cry(-) males have exactly the same phenotype as Ste(+)/cry(-) males. The deletion of all X chromosome Ste copies not only does not eliminate meiotic drive and nondisjunction, but it also does not even reduce them below the levels produced when the X carries 15 copies of Ste.
