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W Stephan

Publications and source records attributed to W Stephan.

At least 55 records · Page 3Linked to original sources
PubMed1993

The advance of Muller's ratchet in a haploid asexual population: approximate solutions based on diffusion theory.

Asexual populations experiencing random genetic drift can accumulate an increasing number of deleterious mutations, a process called Muller's ratchet. We present here diffusion approximations for the rate at which Muller's ratchet advances in asexual haploid populations. The most important parameter of this process is n0 = N e-U/s, where N is population size, U the genomic mutation rate and s the selection coefficient. In a very large population, n0 is the equilibrium size of the mutation-free class. We examined the case n0 > 1 and developed one approximation for intermediate values of N and s and one for large values of N and s. For intermediate values, the expected time at which the ratchet advances increases linearly with n0. For large values, the time increases in a more or less exponential fashion with n0. In addition to n0, s is also an important determinant of the speed of the ratchet. If N and s are intermediate and n0 is fixed, we find that increasing s accelerates the ratchet. In contrast, for a given n0, but large N and s, increasing s slows the ratchet. Except when s is small, results based on our approximations fit well those from computer simulations.

Computer Simulation↗
PubMed1993

RNA folding in Drosophila shows a distance effect for compensatory fitness interactions.

Phylogenetic-comparative analysis was used to construct a secondary structure of Adh precursor messenger RNA (pre-mRNA) in Drosophila. The analysis revealed that the rate of coevolution of base-pairing residues decreases with their physical distance. This result is in qualitative agreement with a model of compensatory fitness interactions which assumes that mutations are individually deleterious but become harmless (neutral) in appropriate combinations. This model predicts that coupled mutations can become fixed in a population under mutation pressure and random genetic drift, when the mutations are closely linked. However, the rate of joint fixation drops as distance between sites increases and recombination breaks up favorable combinations. RNA secondary structure was also used to interpret patterns of linkage disequilibrium at Adh.

Alcohol Dehydrogenase↗
PubMed1993

Analysis of a genetic hitchhiking model, and its application to DNA polymorphism data from Drosophila melanogaster.

Begun and Aquadro have demonstrated that levels of nucleotide variation correlate with recombination rate among 20 gene regions from across the genome of Drosophila melanogaster. It has been suggested that this correlation results from genetic hitchhiking associated with the fixation of strongly selected mutants. The hitchhiking process can be described as a series of two-step events. The first step consists of a strongly selected substitution wiping out linked variation in a population; this is followed by a recovery period in which polymorphism can build up via neutral mutations and random genetic drift. Genetic hitchhiking has previously been modeled as a steady-state process driven by recurring selected substitutions. We show here that the characteristic parameter of this steady-state model is alpha v, the product of selection intensity (alpha = 2Ns) and the frequency of beneficial mutations v (where N is population size and s is the selective advantage of the favored allele). We also demonstrate that the steady-state model describes the hitchhiking process adequately, unless the recombination rate is very low. To estimate alpha v, we use the data of DNA sequence variation from 17 D. melanogaster loci from regions of intermediate to high recombination rates. We find that alpha v is likely to be > 1.3 x 10(-8). Additional data are needed to estimate this parameter more precisely. The estimation of alpha v is important, as this parameter determines the shape of the frequency distribution of strongly selected substitutions.

Animals↗
PubMed1992

Evolutionary consequences of DNA mismatch inhibited repair opportunity.

Double strand breaks (DSBs) are often repaired via homologous recombination. Recombinational repair processes are expected to be influenced by nucleotide heterozygosity through mismatch detection systems. Unrepaired DSBs have severe biological consequences and are often lethal. We show that natural selection due to inhibition of recombinational repair associated with polymorphisms could influence their molecular evolution. The main conclusions from this analysis are that, for increasing population size, mismatch detection leads to a limit on average heterozygosity of otherwise selectively neutral polymorphism, an excess of rare variants, and a slowing down of the rate of neutral molecular evolution. The first two results suggest that mismatch detection may account for the surprisingly narrow range of observed average heterozygosities, given the great variation in population size between species.

Animals↗
PubMed1992

Reduced levels of DNA polymorphism and fixed between-population differences in the centromeric region of Drosophila ananassae.

We have estimated DNA sequence variation within and between two populations of Drosophila ananassae, using six-cutter restriction site variation at vermilion (v) and furrowed (fw). These two gene regions are located close to the centromere on the left and right X chromosome arms, respectively. In the fw region, no DNA polymorphism was detected within each population. In the v region, average heterozygosity per nucleotide was very low in both populations (pi = 0.0005 in the Burma population, and 0.0009 in the India population). These estimates are significantly lower than those from loci in more distal gene regions. The distribution of DNA polymorphisms between both populations was also striking. At fw, three fixed differences between the Burma and India populations were detected (two restriction site differences and one insertion/deletion of approximately 2 kb). At v, each DNA polymorphism in high frequency in the total sample was nearly fixed in one or the other population, although none of them reached complete fixation. The observed pattern of reduced variation within populations and fixed differences between populations appears to correlate with recombination rate. We conclude that recent hitchhiking associated with directional selection is the best explanation for this pattern. The data indicate that different selective sweeps have occurred in the two populations. The possible role of genetic hitchhiking in rapid population differentiation in gene regions of restricted recombination is discussed.

Animals↗
PubMed1990

Molecular evolution of Drosophila metallothionein genes.

The metallothionein genes of Drosophila melanogaster, Mtn and Mto, may play an important role in heavy metal detoxification. Several different tandem duplications of Mtn have been shown to increase cadmium and copper tolerance, as well as Mtn expression. In order to investigate the possibility of increased selection for duplications of these genes in natural populations exposed to high levels of heavy metals, we compared the frequencies of such duplications among flies collected from metal-contaminated and non-contaminated orchards in Pennsylvania, Tennessee and Georgia. Restriction enzyme analysis was used to screen 1666 wild third chromosomes for Mtn duplications and a subset (327) of these lines for Mto duplications. The frequency of pooled Mtn duplications found ranged from 0% to 20%, and was not significantly higher at the contaminated sites. No Mto duplications were identified. Estimates of sequence diversity at the Mtn locus among a subsample (92) of the duplication survey were obtained using four-cutter analysis. This analysis revealed a low level of polymorphism, consistent with both selection at the Mtn locus, and a fairly recent origin for the duplications. To further examine this hypothesis, we sequenced an Mtn allele of Drosophila simulans and measured the amount of nucleotide sequence divergence between D. simulans and its sibling species D. melanogaster. The levels of silent nucleotide polymorphism and divergence in the Mtn region were compared with those in the Adh region, using the neutrality test of R.R. Hudson, M. Kreitman and M. Aguadé.

Alleles↗
PubMed1990

Antibodies from colostrum in oral immunotherapy.

An immunoglobulin preparation for oral use was prepared from pooled bovine colostrum from more than 100 animals. The preparation has high antibacterial antibody titres, and a high capacity for the neutralization of bacterial toxins. It is well tolerated and highly effective in the treatment of severe diarrhoea, e.g. in AIDS patients. The preparation is spray-dried and stable at 2-8 degrees C.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Virus safe plasma exchange medium containing essential human plasma proteins.

CFFP (Coagulation Factor Free Plasma from Biotest) is manufactured under standardized conditions from pooled human plasma of more than 1000 donors per lot. It is sterilized by beta-PL/UV and has not the risks of FFP to transmit viral diseases. CFFP offers desirable advantages as a plasma exchange solution over albumin and FFP as it avoids serious depletions or deviation of normal plasma constituents.

Blood Proteins↗
PubMed1989

Molecular genetic variation in the centromeric region of the X chromosome in three Drosophila ananassae populations. I. Contrasts between the vermilion and forked loci.

We have surveyed three natural populations of Drosophila ananassae for restriction map variation at the forked (f) and vermilion (v) loci, using 6-cutter restriction enzymes. Both loci are located in the centromeric region of the X chromosome. Two major conclusions can be drawn from the data. First, we found strong evidence for population subdivision, i.e., significant differences in the frequency distributions of polymorphisms and/or haplotypes between the Burma, India, and Brazil populations. Secondly, the pattern of DNA sequence variation between the two loci is unexpectedly different. The level of nucleotide variation in the v locus region is reduced (relative to f), especially in the Burma population. Furthermore, in contrast to v, we found no insertions/deletions larger than 700 bp and no significant linkage disequilibrium at f. The genetic differentiation among subpopulations can readily be attributed to restricted migration as the predominant evolutionary force. According to population genetics theory, the differences in DNA polymorphisms between the two loci are in qualitative agreement with the hypothesis that recombination is reduced in the v locus region ("centromere effect") but not at f. In order to test this hypothesis directly, we determined the cytogenetic positions of several loci in the centromeric region by in situ hybridization and found by comparison with the genetic map that recombination at v is indeed very low, much lower than at f.

Animals↗
PubMed1989

Tandem-repetitive noncoding DNA: forms and forces.

A model of sequence-dependent, unequal crossing-over and gene amplification (slippage replication) has been stimulated in order to account for various structural features of tandemly repeated DNA sequences. It is shown that DNA whose sequence is not maintained by natural selection will exhibit repetitive patterns over a wide range of recombination rates as a result of the interaction of unequal crossing-over and slippage replication, processes that depend on sequence similarity. At high crossing-over frequencies, the nucleotide patterns generated in the simulations are simple and highly regular, with short, nearly identical sequences repeated in tandem. Decreasing recombination rates increase the tendency to longer and more-complex repeat units. Periodicities have been observed down to very low recombination rates (one or more orders of magnitude lower than mutation rate). At such low rates, most of the sequences contain repeats which have an extensive substructure and a high degree of heterogeneity among each other; often higher-order structures are superimposed on a tandem array. These results are compared with various structural properties of tandemly repeated DNAs known from eukaryotes, the spectrum ranging from simple-sequence DNAs, particularly the hypervariable mini-satellites, to the classical satellite DNAs, located in chromosomal regions of low recombination, e.g., heterochromatin.

Computer Simulation↗