scholarly journals How good are predictions of the effects of selective sweeps on levels of neutral diversity?

2020 ◽  
Author(s):  
Brian Charlesworth
Keyword(s):  
Recombination Event ◽  
Simple Expression ◽  
Simple Approximation ◽  
Selective Sweeps ◽  
Selection Coefficient ◽  
Wild Type ◽  
X Chromosomes ◽  
Significant Probability ◽  
Coalescent Time ◽  
Multiple Recombination

ABSTRACTSelective sweeps are thought to play a significant role in shaping patterns of variability across genomes; accurate predictions of their effects are, therefore, important for understanding these patterns. A commonly used model of selective sweeps assumes that alleles sampled at the end of a sweep, and that fail to recombine with wild-type haplotypes during the sweep, coalesce instantaneously, leading to a simple expression for sweep effects on diversity. It is shown here that there can be a significant probability that a pair of alleles sampled at the end of a sweep coalesce during the sweep before a recombination event can occur, reducing their expected coalescent time below that given by the simple approximation. Expressions are derived for the expected reductions in pairwise neutral diversities caused by both single and recurrent sweeps in the presence of such within-sweep coalescence, although the effects of multiple recombination events during a sweep are only treated heuristically. The accuracies of the resulting expressions were checked against the results of simulations. For even moderate ratios of the recombination rate to the selection coefficient, the simple approximation can be substantially inaccurate. The selection model used here can be applied to favorable mutations with arbitrary dominance coefficients, to sex-linked loci with sex-specific selection coefficients, and to inbreeding populations. Using the results from this model, the expected differences between the levels of variability on X chromosomes and autosomes with selection at linked sites are discussed, and compared with data on a population of Drosophila melanogaster.

scholarly journals How Good Are Predictions of the Effects of Selective Sweeps on Levels of Neutral Diversity?

Genetics ◽  
2020 ◽  
Vol 216 (4) ◽  
pp. 1217-1238 ◽  
Author(s):  
Brian Charlesworth
Keyword(s):  
Recombination Event ◽  
Simple Expression ◽  
Simple Approximation ◽  
Selective Sweeps ◽  
Selection Coefficient ◽  
Wild Type ◽  
X Chromosomes ◽  
Significant Probability ◽  
Coalescent Time ◽  
Multiple Recombination

Selective sweeps are thought to play a significant role in shaping patterns of variability across genomes; accurate predictions of their effects are, therefore, important for understanding these patterns. A commonly used model of selective sweeps assumes that alleles sampled at the end of a sweep, and that fail to recombine with wild-type haplotypes during the sweep, coalesce instantaneously, leading to a simple expression for sweep effects on diversity. It is shown here that there can be a significant probability that a pair of alleles sampled at the end of a sweep coalesce during the sweep before a recombination event can occur, reducing their expected coalescent time below that given by the simple approximation. Expressions are derived for the expected reductions in pairwise neutral diversities caused by both single and recurrent sweeps in the presence of such within-sweep coalescence, although the effects of multiple recombination events during a sweep are only treated heuristically. The accuracies of the resulting expressions were checked against the results of simulations. For even moderate ratios of the recombination rate to the selection coefficient, the simple approximation can be substantially inaccurate. The selection model used here can be applied to favorable mutations with arbitrary dominance coefficients, to sex-linked loci with sex-specific selection coefficients, and to inbreeding populations. Using the results from this model, the expected differences between the levels of variability on X chromosomes and autosomes with selection at linked sites are discussed, and compared with data on a population of Drosophila melanogaster.

scholarly journals UNEQUAL CROSSING OVER AT THE rRNA TANDON AS A SOURCE OF QUANTITATIVE GENETIC VARIATION IN DROSOPHILA

Genetics ◽  
1980 ◽  
Vol 95 (3) ◽  
pp. 727-742 ◽  
Author(s):  
R Frankham ◽  
D A Briscoe ◽  
R K Nurthen
Keyword(s):  
Genetic Variation ◽  
Selection Response ◽  
Crossing Over ◽  
Wild Type ◽  
X Chromosomes ◽  
Unequal Crossing Over ◽  
Quantitative Genetic ◽  
Y Chromosomes ◽  
Homozygous Line ◽  
Minimum Estimate

ABSTRACT Abdominal bristle selection lines (three high and three low) and controls were founded from a marked homozygous line to measure the contribution of sex-linked "mutations" to selection response. Two of the low lines exhibited a period of rapid response to selection in females, but not in males. There were corresponding changes in female variance, in heritabilities in females, in the sex ratio (a deficiency of females) and in fitness, as well as the appearance of a mutant phenotype in females of one line. All of these changes were due to bb alleles (partial deficiencies for the rRNA tandon) in the X chromosomes of these lines, while the Y chromosomes remained wild-type bb+. We argue that the bb alleles arose by unequal crossing over in the rRNA tandon.—A prediction of this hypothesis is that further changes can occur in the rRNA tandon as selection is continued. This has now been shown to occur.—Our minimum estimate of the rate of occurrence of changes at the rRNA tandon is 3 × 10-4. As this is substantially higher than conventional mutation rates, the questions of the mechanisms and rates of origin of new quantitative genetic variation require careful re-examination.

Chromosomal Patterns of Microsatellite Variability Contrast Sharply in African and Non-African Populations of Drosophila melanogaster

Genetics ◽  
2002 ◽  
Vol 160 (1) ◽  
pp. 247-256
Author(s):  
M Kauer ◽  
B Zangerl ◽  
D Dieringer ◽  
C Schlötterer
Keyword(s):  
Chromosomal Polymorphism ◽  
Background Selection ◽  
Selective Sweeps ◽  
X Chromosomes ◽  
Evolutionary Forces ◽  
Relative Contribution ◽  
African Populations ◽  
Neutral Variation ◽  
Colonization Process ◽  
The Subject

Abstract Levels of neutral variation are influenced by background selection and hitchhiking. The relative contribution of these evolutionary forces to the distribution of neutral variation is still the subject of ongoing debates. Using 133 microsatellites, we determined levels of variability on X chromosomes and autosomes in African and non-African D. melanogaster populations. In the ancestral African populations microsatellite variability was higher on X chromosomes than on autosomes. In non-African populations X-linked polymorphism is significantly more reduced than autosomal variation. In non-African populations we observed a significant positive correlation between X chromosomal polymorphism and recombination rate. These results are consistent with the interpretation that background selection shapes levels of neutral variability in the ancestral populations, while the pattern in derived populations is determined by multiple selective sweeps during the colonization process. Further research, however, is required to investigate the influence of inversion polymorphisms and unequal sex ratios.

scholarly journals Decreased Virus Population Diversity in p53-Null Mice Infected with Weakly Oncogenic Abelson Virus

2005 ◽  
Vol 79 (18) ◽  
pp. 11618-11626 ◽  
Author(s):  
Erica Marchlik ◽  
Richard Kalman ◽  
Naomi Rosenberg
Keyword(s):  
Tumor Suppressor ◽  
Recombination Event ◽  
Leukemia Virus ◽  
Population Diversity ◽  
Virus Population ◽  
Wild Type ◽  
Emerging Viruses ◽  
Host Genes ◽  
Murine Leukemia

ABSTRACT The Abelson murine leukemia virus (Ab-MLV), like other retroviruses that contain v-onc genes, arose following a recombination event between a replicating retrovirus and a cellular oncogene. Although experimentally validated models have been presented to address the mechanism by which oncogene capture occurs, very little is known about the events that influence emerging viruses following the recombination event that incorporates the cellular sequences. One feature that may play a role is the genetic makeup of the host in which the virus arises; a number of host genes, including oncogenes and tumor suppressor genes, have been shown to affect the pathogenesis of many murine leukemia viruses. To examine how a host gene might affect an emerging v-onc gene-containing retrovirus, we studied the weakly oncogenic Ab-MLV-P90A strain, a mutant that generates highly oncogenic variants in vivo, and compared the viral populations in normal mice and mice lacking the p53 tumor suppressor gene. While variants arose in both p53 +/+ and p53 − / − tumors, the samples from the wild-type animals contained a more diverse virus population. Differences in virus population diversity were not observed when wild-type and null animals were infected with a highly oncogenic wild-type strain of Ab-MLV. These results indicate that p53, and presumably other host genes, affects the selective forces that operate on virus populations in vivo and likely influences the evolution of oncogenic retroviruses such as Ab-MLV.

scholarly journals CORRIGENDUM

Genetics ◽  
1987 ◽  
Vol 115 (3) ◽  
pp. 579-579
Keyword(s):  
Sister Chromatid ◽  
Recombination Event ◽  
Linear Plasmid ◽  
Wild Type ◽  
Spore Viability ◽  
Yeast Plasmid ◽  
Type Locus ◽  
Sister Chromatids ◽  
Chromosome Ii ◽  
Meiosis I

ABSTRACT In the paper by Jules O'Rear and Jasper Rine (Genetics  113: 517-529; July, 1986) entitled "Precocious meiotic centromere separation of a novel yeast chromosome," the authors described a gene conversion event between a linear yeast plasmid carrying a LYS2 gene and a mutant lys2 gene at the wild-type locus on chromosome II. When these yeasts were mated to wild-type yeast and the resulting diploids sporulated, linked markers on the linear plasmid showed unusual segregation and poor spore viability was observed. On the basis of these observations, we proposed that the recombination event between the linear plasmid and chromosome II had split chromosome II into two fragments, one of which carried the normal centromere of chromosome II (fragment IIa) and the other, a telocentric fragment (fragment IIb), carried the centromere present on the linear plasmid. Separation of the chromosomes from these cells on OFAGE gels verified that chromosome II had been split into two fragments. Furthermore, we proposed that the sister chromatids of the telocentric fragment (fragment IIb) separated precociously in meiosis I when complete chromosome II and fragment IIa were present. In discussions with colleagues, an alternative explanation arose in which a recombination event between a sister chromatid of fragment IIa and a sister chromatid of chromosome II would result in each chromosome II chromatid being joined to a fragment IIa chromatid at CEN2. The two daughter cells of meiosis I would therefore each receive one chromatid of fragment IIa and one chromatid of chromosome II. Segregation of the two sister chromatids of fragment IIb to one pole in meiosis I without precocious centromere separation would result in the observed tetrad classes. To distinguish between these two mechanisms, a centromere-linked marker was introduced into the cross between the strain containing the two fragments of chromosome II and a wild-type strain. Tetrad analysis of the resulting diploid is consistent with the recombination model for the poor spore viability and inconsistent with precocious centromere separation. We thank Drs. Eric Lambie, Michael Lichten and Tom Petes for helpful discussions.

scholarly journals Histochemical differences in expression of X-linked glucose-6-phosphate dehydrogenase between ectoderm- and endoderm-derived embryonic and extra-embryonic tissues.

1991 ◽  
Vol 39 (5) ◽  
pp. 569-574 ◽  
Author(s):  
H Sobis ◽  
A Verstuyf ◽  
M Vandeputte
Keyword(s):  
X Chromosome ◽  
Yolk Sac ◽  
Wild Type ◽  
X Chromosomes ◽  
Tissue Sections ◽  
C3h Mice ◽  
Visceral Yolk Sac ◽  
Enzyme Deficient ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Derivatives Of

We examined the activity of X-linked glucose-6-phosphate dehydrogenase (G6PD) in concepti of the enzyme-deficient mutant and wild-type C3H mice. By using different crosses between the G6PD-deficient homozygous, heterozygous, or wild-type females and hemizygous or wild-type males, we confirmed the inactivation of one of the two X chromosomes in female concepti by a histochemical method. With this technique, a dual (G6PD + or -) cell population could be observed in the tissue sections. We demonstrate that the paternal X chromosome is inactivated in the endoderm of parietal and visceral yolk sac and in the trophoblast, whereas in the embryo and in the yolk sac mesoderm this inactivation is random. Our results confirm biochemical observations showing that only the maternal X chromosome is expressed in all derivatives of trophectoderm and primitive endoderm, whereas derivatives of the primitive ectoderm show random X chromosome expression.

scholarly journals Sγ3 switch sequences function in place of endogenous Sγ1 to mediate antibody class switching

2008 ◽  
Vol 205 (7) ◽  
pp. 1567-1572 ◽  
Author(s):  
Ali A. Zarrin ◽  
Peter H. Goff ◽  
Kate Senger ◽  
Frederick W. Alt
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Recombination Event ◽  
Class Switch Recombination ◽  
Constant Region ◽  
Wild Type ◽  
Class Switch ◽  
Specific Factors ◽  
Antibody Class

Immunoglobulin heavy chain (IgH) class switch recombination (CSR) replaces the initially expressed IgH Cμ exons with a set of downstream IgH constant region (CH) exons. Individual sets of CH exons are flanked upstream by long (1–10-kb) repetitive switch (S) regions, with CSR involving a deletional recombination event between the donor Sμ region and a downstream S region. Targeting CSR to specific S regions might be mediated by S region–specific factors. To test the role of endogenous S region sequences in targeting specific CSR events, we generated mutant B cells in which the endogenous 10-kb Sγ1 region was replaced with wild-type (WT) or synthetic 2-kb Sγ3 sequences or a synthetic 2-kb Sγ1 sequence. We found that both the inserted endogenous and synthetic Sγ3 sequences functioned similarly to a size-matched synthetic Sγ1 sequence to mediate substantial CSR to IgG1 in mutant B cells activated under conditions that stimulate IgG1 switching in WT B cells. We conclude that Sγ3 can function similarly to Sγ1 in mediating endogenous CSR to IgG1. The approach that we have developed will facilitate assays for IgH isotype–specific functions of other endogenous S regions.

scholarly journals Effects of poly[d(pGpT).d(pApC)] and poly[d(pCpG).d(pCpG)] repeats on homologous recombination in somatic cells.

1986 ◽  
Vol 6 (11) ◽  
pp. 3948-3953 ◽  
Author(s):  
P Bullock ◽  
J Miller ◽  
M Botchan
Keyword(s):  
Homologous Recombination ◽  
Recombination Event ◽  
Somatic Cells ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Wild Type ◽  
Recombination Product ◽  
Homologous Recombination Event ◽  
Sequencing Studies ◽  
Purine Pyrimidine

Sequencing studies have shown that in somatic cells alternating runs of purines and pyrimidines are frequently associated with recombination crossover points. To test whether such sequences actually promote recombination, we have examined the effects of poly[d(pGpT).d(pApC)] and poly[d(pCpG).d(pCpG)] repeats on a homologous recombination event. The parental molecule used in this study, pSVLD, is capable of generating wild-type simian virus 40 DNA via recombination across two 751-base-pair regions of homology and has been described previously (Miller et al., Proc. Natl. Acad. Sci. USA 81:7534-7538, 1984). Single inserts of either a poly[d(pGpT).d(pApC)] repeat or a poly[d(pCpG).d(pCpG)] repeat were positioned adjacent to one region of homology in such a way that the recombination product, wild-type simian virus 40 DNA, could be formed only by recombination within the homologies and not by recombination across the alternating purine-pyrimidine repeats. We have found that upon transfection of test DNAs into simian cells, a poly[d(pCpG).d(pCpG)] repeat enhanced homologous recombination 10- to 15-fold, whereas a poly[d(pGpT).d(pApC)] repeat had less effect. These results are discussed in terms of the features of these repeats that might be responsible for promoting homologous recombination.

P32-INDUCED LETHAL MUTATIONS IN DROSOPHILA

1951 ◽  
Vol 29 (3) ◽  
pp. 234-239 ◽  
Author(s):  
T. J. Arnason ◽  
R. L. Irwin ◽  
J. W. T. Spinks
Keyword(s):  
X Rays ◽  
Total Radiation ◽  
Wild Type ◽  
Larval Food ◽  
X Chromosomes ◽  
Recessive Lethal ◽  
Initial Concentration ◽  
Lethal Mutations ◽  
Total Radiation Dose ◽  
Food Medium

X-chromosomes of P32-treated wild-type Drosophila melanogaster were tested for the presence of recessive lethal mutations. Treated larvae were reared in food medium containing initially 6.5, 32.5, 65.0, or 162.5 mrd. P32 per ml. Of 838 tested chromosomes 42 had recessive lethals. The frequency of mutation was roughly proportional to P32 content of the food. An initial concentration of 18.8 mrd. P32 in larval food is expected to produce about the same frequency of recessive lethal mutations as is obtained with 1000 r. of X rays applied to mature sperm. A fly reared in medium having an initial concentration of 32.5 mrd. per ml. receives, prior to mating, a calculated total radiation dose of 0.62 gram roentgens. At this dosage 4.2% recessive lethals were recorded. For equivalent amounts of ionization P32 is here apparently 2.3 times as effective as X rays.

scholarly journals Unequal crossing-over within the B duplication of Drosophila melanogaster: a molecular analysis

1991 ◽  
Vol 57 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Stuart I. Tsubota
Keyword(s):  
Drosophila Melanogaster ◽  
Transposable Element ◽  
Molecular Analysis ◽  
Recombination Event ◽  
Tandem Duplication ◽  
Molecular Data ◽  
Crossing Over ◽  
Wild Type ◽  
Unequal Crossing Over ◽  
Extreme Form

SummaryThe B mutation is associated with a tandem duplication of 16A1–16A7. It is unstable, mutating to wild type and to a more extreme form at a frequency of one in 1000 to 3000. The reversion to wild type is associated with the loss of one copy of the duplication, whereas the mutation to extreme B is associated with a triplication of the region. The instability of B has been attributed to unequal crossing-over between the two copies of the duplication. Recent molecular data show that there is a transposable element, B104, between the two copies of the duplication and support the hypothesis that this element generated the duplication via a recombination event. These data suggest that unequal crossing-over within the duplication may not be the cause of the instability of B. Instead, the instability may be caused by a recombination event involving the B104 element. This issue was addressed using probes for the DNA on either side of the B104 element at the B breakpoint. All of the data indicate that the B104 element is not involved in the instability of B and support the original unequal crossing-over model.

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