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W J Ewens

Publications and source records attributed to W J Ewens.

18 recordsLinked to original sources

An optimizing principle of natural selection in evolutionary population genetics.

This paper brings together two themes in evolutionary population genetics theory. The first concerns Fisher's Fundamental Theorem of Natural Selection: a recent interpretation of this theorem claims that it is an exact result, relating to the so-called "partial" increase in mean fitness. The second theme concerns the desire to find an optimality principle in genetic evolution. Such a principle is found here: of all gene frequency changes which lead to the same partial increase in mean fitness as the natural selection gene frequency changes, the natural selection values minimize a generalized distance measure between parent and daughter generation gene frequency values.

Alleles

Statistical analysis of in situ hybridization data: derivation and use of the zmax test.

There are many situations in which grain distributions resulting from in situ hybridization of radioactively labeled probes to unique genes should be subjected to a statistical analysis. However, the problems posed by analysis of in situ hybridization data are not straightforward, and no completely satisfying method is currently available. We have developed a procedure in which the major and any number of minor site(s) of hybridization may be specifically located and the significance of each tested. This zmax procedure first tests the overall distribution for departure from randomness and then identifies significantly overlabeled whole chromosomes (or chromosome arms or other large segments), a process that may be repeated to pinpoint significantly overlabeled regions within these chromosomes. We describe in detail the derivation of the zmax statistic, present tables of significant zmax levels, and show with examples how zmax is used in tests of significance of in situ hybridization data.

Animals

Genome mapping with anchored clones: theoretical aspects.

As part of our effort to construct a physical map of the genome of Arabidopsis thaliana we have made a mathematical analysis of our experimental approach of anchoring yeast artificial chromosome clones with genetically mapped RFLPs and RAPDs. The details of this analysis are presented and their implications for mapping the Arabidopsis genome are discussed.

Chromosome Mapping

Remarks on ascertainment.

Genetic Analysis Workshop data come from various sources, with possibly different ascertainment procedures in each. It is plausible that classical ascertainment models do not accurately describe the ascertainment process in each data source. For this reason, we review the biases which can arise from an incorrect specification on the ascertainment process and discuss their relevance for the GAW5 data analysis.

Child

An interpretation and proof of the Fundamental Theorem of Natural Selection.

Fisher's "Fundamental Theorem of Natural Selection" has long caused controversy in population genetics theory. Viewed as a statement about the increase, or rate of increase, of mean fitness over time, it encounters difficulties with cases arising in a multi-locus system for which mean fitness can decrease. An interpretation of the theorem is put forward here which implies that it is correct as a mathematical statement, but of less biological value than was claimed by Fisher.

Gene Frequency

Is knowing the age-order of alleles in a sample useful in testing for selective neutrality?

The most powerful, and most frequently used, test of selective neutrality, based on data consisting of observed allelic frequencies in a sample of genes at some locus, is the procedure of G. A. Watterson. This procedure uses the sample homozygosity F* as the test statistic, and in effect leads to rejection of the hypothesis of selective neutrality if the observed value of F* differs significantly from neutral theory expectations. The homozygosity statistic is invariant under relabeling of the alleles and thus cannot use any further information on the alleles which might be available. We present results which suggest that information concerning the age order of the alleles cannot be used to provide a more powerful testing procedure than that of Watterson.

Alleles

A resolution of the ascertainment sampling problem: IV. Continuous phenotypes.

This paper considers ascertainment corrections for continuous phenotypes. Two main points are considered. The first is a discussion of what ascertainment corrections can be devised to ensure asymptotically unbiased parameter estimates when the nature of the ascertainment procedure is not known. The second is an analysis of the properties of various forms of ascertainment correction possible when the nature of the ascertainment procedure is known. Some ascertainment corrections are thus shown to be valid and others invalid.

Data Interpretation, Statistical

A resolution of the ascertainment sampling problem. II. Generalizations and numerical results.

The ascertainment problem arises when families are sampled by a nonrandom process and some assumption about this sampling process must be made in order to estimate genetic parameters. Under classical ascertainment assumptions, estimation of genetic parameters cannot be separated from estimation of the parameters of the ascertainment process, so that any misspecification of the ascertainment process causes biases in estimation of the genetic parameters. Ewens and Shute proposed a resolution to this problem, involving conditioning the likelihood of the sample on the part of the data which is "relevant to ascertainment." The usefulness of this approach can only be assessed by examining the properties (in particular, bias and standard error) of the estimates which arise by using it for a wide range of parameter values and family size distributions and then comparing these biases and standard errors with those arising under classical ascertainment procedures. These comparisons are carried out in the present paper, and we also compare the proposed method with procedures which condition on, or ignore, parts of the data.

Data Interpretation, Statistical

A resolution of the ascertainment sampling problem. III. Pedigrees.

When nuclear families are sampled by an ascertainment procedure whose properties are not known, biased estimates of genetic parameters will arise if an incorrect specification of the ascertainment procedure is made. Elsewhere we have put forward a resolution of this problem by introducing an ascertainment-assumption-free (AAF) method, for nuclear family data, which gives asymptotically unbiased estimators no matter what the true nature of the ascertainment process. In the present paper we extend this method to cover pedigree data. Problems that arise with pedigrees but not with families--for example, the question of which families in a pedigree are "ascertainable"--are also considered. Comparisons of numerical results for pedigrees and nuclear families are also made.

Data Interpretation, Statistical

Multifactorial analysis of family data ascertained through truncation: a comparative evaluation of two methods of statistical inference.

When family data are ascertained through single selection based on truncation, a prevailing method of analysis is to condition the likelihood function on the proband's actual phenotypic value. An alternative method conditions the likelihood function on the event that the proband's measurement lies in the truncation region. Both methods are contrasted here by using Monte Carlo simulations; identical sets of data were analyzed using both methods. The results suggest that, under either method, (1) parameter estimates are nearly unbiased and (2) likelihood-ratio tests of null hypotheses are approximately distributed as chi 2. However, conditioning on the proband's actual phenotypic value yields considerably less efficient estimates and reduced power for hypothesis tests. A corresponding result also holds under complete ascertainment. It is argued, therefore, that whenever sufficient information is available on the nature of truncation, the alternative approach should be used.

Computer Simulation

Effects of ovine follicular fluid on plasma LH and FSH secretion in ovariectomized ewes to indicate the site of action of inhibin.

Ovariectomized ewes were given 2 ml s.c. injections of ovine follicular fluid (oFF) (N = 3) or serum (N = 3) and blood samples were collected each day for 3 days. Follicular fluid caused a significant (P less than 0.005) reduction in FSH within 1 day, but did not affect mean LH values. Two groups of 3 ewes were treated as above but sampled intensively (each 10 min for 6 h) on Days 1 (before treatment) and 4; mean plasma FSH concentration and plasma LH pulse frequency and amplitude were ascertained. Significant (P less than 0.005) reduction of FSH concentration was seen in the oFF-treated ewes. A non-specific reduction in LH pulse amplitude, but not pulse frequency, was noted in the control ewes. This experiment was repeated with 2 groups of 4 ewes that were conditioned to the experimental environment and effects on LH secretion were not observed in the controls given serum. Treatment with oFF caused a 70% reduction (P less than 0.005) in plasma FSH and a small (30%) but significant (P less than 0.005) reduction in mean LH concentrations. The latter was probably associated with a reduction in LH pulse amplitude in 3/4 animals (N.S.) with no change in LH pulse frequency. Treatment with oFF, as in Exp. 1, caused a 95% reduction in FSH values and significant (P less than 0.01) reduction (32%) of LH pulse amplitude in ovariectomized ewes that had been subjected to hypothalamo-pituitary disconnection and in which gonadotrophin secretion was reinstated with pulses of 250 ng GnRH every 2 h. These results suggest that proteins from the sheep follicular fluid, including inhibin, act at the pituitary level to inhibit FSH secretion and may have some effects on LH pulse amplitude.

Animals

Properties of equilibria in multi-locus genetic systems.

The classical mathematical theory of population genetics considered, for simplicity, almost exclusively one-locus systems. In the last two decades much work has been done on two-locus and, less frequently, multi-locus systems. This research has usually involved investigating properties of systems with given, and usually rather special, fitness parameters. Real genetic fitness systems are undoubtedly multi-locus and seldom will possess simplifying characteristics. One aim of this paper is to study generalized systems where no special assumptions are made about fitness structure, the number of alleles at each locus, the number of loci involved or the recombination structure between loci. A second aim is to consider marginal properties (often one-locus properties) of complex systems: the fact that many observations involve data from only on locus makes this second aim relevant.

Alleles

Remarks on the evolutionary effect of natural selection.

The so-called "Fundamental Theorem of Natural Selectiion", than the mean fitness of a population increases with time under natural selection, is known not to be true, as a mathematical theorem, when fitnesses depend on more than one locus. Although this observation may not have particular biological relevance, (so that mean fitness may well increase in the great majority of interesting situations), it does suggest that it is of interest to find an evolutionary result which is correct as a mathematical theorem, no matter how many loci are involved. The aim of the present note is to prove an evolutionary theorem relating to the variance in fitness, rather that the mean: this theorem is true for an arbitrary number of loci, as well as for arbitrary (fixed) fitness parameters and arbitrary linkage between loci. Connections are briefly discussed between this theorem and the principle of quasi-linkage equilibrium.

Biological Evolution

A note on the variance of the number of loci having a given gene frequency.

In a recent not in this journal (MARUYAMA 1973), one of us has considered, for a certain genetic model, the variance of the distribution of the number of loci having a given gene frequency. The formula given is incorrect. This brief note considers this problem and notes the correct solution in one particular case.

Analysis of Variance