Oliver Mayo

THE EVOLUTION OF DOMINANCE: A THEORY WHOSE TIME HAS PASSED?

The evolution of dominance by the selection of modifiers of the phenotypes of deleterious mutations was proposed as a hypothesis by R. A. Fisher in 1928. It has been strongly criticized ever since, is regarded by many as having been made irrelevant by metabolic control theory, and most recently has been claimed to have been‘falsified’by H. A. Orr. Is it indeed not only obsolete but wrong? Its history is reviewed and its present status evaluated. We conclude (1) that it has a role as the explanation of the dominance found in many cases of selection through visual predation and (2) that the selection mechanism long claimed to be ineffective (the increase in frequency of a single modifier) will be effective under certain special conditions that may be different from those Fisher proposed.

A century of Hardy-Weinberg equilibrium.

Hardy-Weinberg equilibrium (HWE) is the state of the genotypic frequency of two alleles of one autosomal gene locus after one discrete generation of random mating in an indefinitely large population: if the alleles are A and a with frequencies p and q(=1-p), then the equilibrium gene frequencies are simply p and q and the equilibrium genotypic frequencies for AA, Aa and aa are p2, 2pq and q2. It was independently identified in 1908 by G. H. Hardy and W. Weinberg after earlier attempts by W. E. Castle and K. Pearson. Weinberg, well known for pioneering studies of twins, made many important contributions to genetics, especially human genetics. Existence of this equilibrium provides a reference point against which the effects of selection, linkage, mutation, inbreeding and chance can be detected and estimated. Its discovery marked the initiation of population genetics.

The Rise and Fall of the Common Disease-common Variant (CD-CV) Hypothesis: How the Sickle Cell Disease Paradigm Led Us All Astray (Or Did It?)

The common disease-common variant (CD-CV) hypothesis requires an explanation for the origin of the variation observed, since substantial neutral, but not deleterious, variation, that is, several alleles each at moderate to high frequency, can be maintained at any gene/locus by mutation. It is argued here that the guiding principle, not always stated, has been balancing selection, influenced by the well-established cases of deleterious alleles maintained through heterozygous advantage in the face of strong malarial selection against normal alleles. It is further argued that, although balanced polymorphisms have indeed arisen and reduced population loss through infectious disease, the history of balance in other contexts should have prevented acceptance of any hypothesis that generalized such a specific mechanism. Finally, it is suggested that in the present state of knowledge no single hypothesis for the genetical contribution to common disorders is justifiable.

Early research on human genetics using the twin method: who really invented the method?

The twin method consists of a formal comparison between the resemblance between identical (monozygotic, MZ) twins and the resemblance between fraternal (dizygotic, DZ) twins for some trait of interest. It was developed between 1900 and about 1940, as more accurate tools for diagnosis of zygosity and for statistically analyzing the resemblance between relatives were built. Its early use was in the demonstration that a trait was inherited or that part of the causation of a trait was genetical, but it has now evolved to the point that twin registries constitute an important resource for the identification of specific genes and their interactions both with other genes and with the internal and external environment. Who really invented the method is still an unsettled question, which this article explores.

Charles Darwin as Experimenter: One of Many Reasons to Remember him at 200

Abstract The paper is divided into three parts. First, Darwin’s contribution is briefly reviewed, by considering the thoughts of some of his critics, from his own time to today. Secondly, Darwin’s creativity and precision as an experimenter are illustrated through a consideration of a series of experiments on mentation in earthworms. Finally, an Adelaide connexion is discussed, for the light it sheds on the reception of Darwin’s greatest work.

Fisher in Adelaide

R. A. Fisher spent much of his final 3 years of life in Adelaide. It was a congenial place to live and work, and he was much in demand as a speaker, in Australia and overseas. It was, however, a difficult time for him because of the sustained criticism of fiducial inference from the early 1950s onwards. The article discusses some of Fishers work on inference from an Adelaide perspective. It also considers some of the successes arising from this time, in the statistics of field experimentation and in evolutionary genetics. A few personal recollections of Fisher as houseguest are provided. This article is the text of a article presented on August 31, 2012 at the 26th International Biometric Conference, Kobe, Japan.

The Origin, Extent and Persistence of Variation: Is the ‘Origin of Variation’ the ‘Origin of Species’?

Abstract Variation is necessary for evolution by natural selection, but is not the cause in any other sense. Natural selection is the main causal factor, but available genetic variation and environmental constraints determine the path taken. Variation persists through mutation, the regularity of the genetical replication system and population size.

Interaction between Genotype and Environment: A Tale of Two Concepts

Abstract Fisher’s (1918) linear model for quantitative inheritance has been extraordinarily successful, even though it was attacked, correctly, by Hogben (1933) as unsuitable for the analysis of traits manifesting non-linear interactions, which were likely to be common, not rare. This prediction has been confirmed. The robustness and success of the linear model, especially for short-term prediction in applied genetics, should not be allowed to obscure its difficulties when multivariate methods can replace it and the data on which to use them are available.