Recipient of the 2011 Molecular Ecology Prize: Deborah Charlesworth

inline image

For the past 35 years, Professor Deborah Charlesworth (University of Edinburgh) has been a pioneer in the fields of evolutionary genetics, plant population genetics and the evolution of plant sexual systems. She has made seminal contributions to our understanding of the evolutionary importance of recombination and inbreeding depression, and the evolution of sex chromosomes in plants. By tightly linking theoretical population genetics with empirical work in plants, she has been able to simultaneously bring population genetic theory to bear on key questions in plant evolution, as well as bring plants to the forefront as important model systems for testing fundamental questions in evolutionary biology.

Deborah was initially trained in biochemistry, although from the beginning the characterization of genetic variation was a component of her research. She obtained her doctorate at Cambridge (1968) with a thesis on the quantitative genetics of mice, particularly the extent of genetic variation in blood glucose levels across natural strains, the topic of her first study (Charlesworth 1969). Her subsequent work at Cambridge and Chicago as a research fellow in human genetics examined amino acid variation in haemoglobins in human populations.

Deborah’s research interests turned fully to evolutionary biology as she began to collaborate with Brian Charlesworth. In particular, it was theoretical work on the evolution of mimicry systems (Charlesworth & Charlesworth 1975) and recombination rates (Charlesworth et al. 1977) that inspired her to pursue evolution over the long term. Since then, Deborah and Brian have been leaders in the field of evolutionary theory, by integrating computer simulation, analytical models and empirical evidence to provide carefully reasoned insights into the evolutionary process.

One of the most surprising features of Deborah’s scientific career is that she did not have a permanent position for 20 years after obtaining her PhD. As Brian took up positions in Liverpool, Sussex and Chicago, Deborah continued to do research without grant support (being ineligible to apply without a faculty position). By the time she obtained a professorship at Chicago in 1988, Deborah had already published ∼50 articles, many of which are citation classics and have had a tremendous influence on various fields. Today Deborah is a Fellow of the Royal Society of London and the Royal Society of Edinburgh, and has been the President of both the European Society for the Study of Evolution, and the Society for Molecular Biology and Evolution.

Deborah’s early models of mimicry (Charlesworth & Charlesworth 1975) and the evolution of recombination rates (Charlesworth et al. 1977) launched a career-long interest into the evolutionary consequences of recombination. These studies explored two distinct scenarios; cases where recombination can be advantageous, by generating new favourable combinations of alleles, but also situations where recombination can be selected against or hinder adaptation, when it creates low-fitness combinations. This latter scenario occurs in the classic case of Batesian mimicry, where a palatable species mimics the warning signals of multiple unpalatable species to avoid predation. In butterflies, mimicry is controlled by a ‘supergene’, where multiple linked genes control a suite of characteristics allowing the mimic to resemble its model. In this system, recombination is disadvantageous because it will generate intermediate phenotypes that do not resemble poisonous model species and therefore will be subject to predation. Theoretical work by Deborah and Brian showed that supergenes are much more likely to have arisen on the same chromosome initially (i.e. they were partially linked to begin with), with the possibility of further selection favouring subsequent modifiers suppressing recombination. The ongoing relevance of this model to nature was highlighted recently when it was discovered that suppressed recombination at the mimicry supergene in Heliconius numata was maintained by a chromosomal inversion (Joron et al. 2011).

Understanding the dynamics of supergene systems subject to selection for recombination suppression became a central focus of Deborah’s theoretical work in subsequent years. In particular, the puzzle of how multiple genes end up linked together in a coordinated and complex polymorphism, and the importance of ‘linkage constraint’ on their evolution became relevant when trying to understand other biological phenomena. This applies, for example, to questions about the evolution of separate sexes and sex chromosomes (Charlesworth & Charlesworth 1978), which require the fixation of both a gene controlling male sterility and a second locus controlling female sterility. It is also relevant when considering the evolution of heteromorphic (Charlesworth & Charlesworth 1979) self-incompatibility systems in flowering plants.

Another major focus of Deborah’s theoretical work is the evolutionary significance of deleterious mutations. The inverse of the advantages of recombination suppression is that reduced recombination can lead to a reduction in diversity and the accumulation of deleterious mutations. This has important consequences during the evolution of sex chromosomes, as well as for the evolution of self-fertilization. Theoretical work on ‘background selection’, the reduction of neutral diversity owing to the recurrent elimination of deleterious mutations (Charlesworth et al. 1993), has become recognized as a dominant process structuring patterns of genetic variation and the efficacy of natural selection across the genome. Deborah’s theoretical work on the evolution of selfing and outcrossing (Charlesworth et al. 1990) and the evolution of separate sexes (Charlesworth & Charlesworth 1978) also highlighted the importance of inbreeding depression owing to segregating deleterious mutations as a primary determinant of the evolution of sexual systems. The major importance of inbreeding depression as a driver of evolutionary change was laid out in a major review article (Charlesworth & Charlesworth 1987; currently 1558 citations) that helped to stimulate whole research programs focused on measuring and comparing its strength.

Deborah has carried out research in areas that extend well beyond those emphasized here. Indeed, as an undergraduate and starting graduate student, I began to wonder whether there was any possible topic I could get interested in that Deborah had not written about. I really thought I was onto something new when I wanted to look at the evolution of transposable elements for graduate work, only to discover that Deborah and Brian had written an outstanding theoretical treatment on this topic in 1983 (Charlesworth & Charlesworth 1983).

In addition to being a successful theoretician, Deborah has developed several plant groups (e.g. Leavenworthia, Silene) as model systems for studying molecular population genetics and molecular evolution, always with an eye to testing theoretical models. As a prime example, she was the first to use plants for the study of molecular evolution of sex chromosomes in order to test the prediction that recombination suppression on Y chromosomes should lead to deleterious mutation accumulation and gene degeneration. She recognized the particular utility of plants in this regard; most mammalian and insect sex chromosome systems are ancient, and so we are often looking at the very end-point of this process. To really understand the process of recombination suppression, and understand the process of Y-chromosome degeneration, plants provide suitable experimental material, as sex chromosome systems tend to be much younger and have evolved multiple times independently. Focusing on the dioecious species Silene latifolia, Deborah’s research group identified the first sex-linked gene in plants (Guttman and Charlesworth 1998), and subsequent work has led to detailed characterization indicating the spread of recombination suppression (Bergero et al. 2007), Y chromosome degeneration (Marais et al. 2008), reduced diversity (Filatov et al. 2000), loss of expression (Marais et al. 2008) and transposable element accumulation in Y-linked genes (Bergero et al. 2008). Additional recent empirical work has focused on understanding the selective dynamics and testing for recombination suppression at the self-incompatibility locus (e.g. Kamau & Charlesworth 2005) and investigating the population genetic and molecular evolutionary consequences of self-fertilization and low recombination in Leavenworthia and Arabidopsis (Liu et al. 1999; Kawabe et al. 2008; Qiu et al. 2011).

Although officially retired, Deborah has been as productive and innovative as she was during the first 20 years before having an ‘official’ position. The latest work from her laboratory takes a novel approach using next-generation sequencing to perform a high-throughput screen for large numbers of sex-linked genes in Silene (Bergero & Charlesworth 2011). The results show evidence of both the accumulation of deleterious mutations on Y-linked chromosomes and a slower rate of degeneration than ‘neo-Y’ systems in Drosophila. These results suggest the importance of gametic selection in slowing down sex chromosome evolution in plants, as well as the slower rate of degeneration on an original Y chromosome that is experiencing the process of protracted recombination suppression.

Writing as a former graduate student in her laboratory at Edinburgh, I can attest to the fact that Deborah is highly supportive of students at all stages in their academic development. As an example, she is known to carefully read many research posters at conferences and spend time with students providing constructive comments about their results. During her time at both Chicago and Edinburgh, she has been primary advisor of 11 graduate students and 21 postdoctoral fellows, many of whom are now making major contributions in evolutionary genetics. To name just a few, past trainees include Philip Awadalla (University of Montreal), Johanne Brunet (University of Wisconsin), Dmitry Filatov (Oxford University), Jenny Hagenblad (Uppsala University), Barbara Mable (University of Glasgow), Gabriel Marais (University of Lyon), Magnus Nordborg (Gregor Mendel Institute), Mikkel Schierup (Aarhus University) and John Willis (Duke University). A striking example of Deborah’s breadth of training is found in my own Department of Ecology and Evolutionary Biology at the University of Toronto, where three faculty are past trainees from her laboratory (Asher Cutter, David Guttman and myself) and a fourth, Spencer Barrett, collaborated with Deborah on an experimental test of purging of deleterious mutations following inbreeding (Barrett & Charlesworth 1991). Few evolutionary geneticists have had such a wide influence and played such an important role in the training of today’s workers in the field. The recent textbook on evolutionary genetics by the Charlesworths (Charlesworth & Charlesworth 2010) represents the definitive treatise in this field, and they have also contributed an important popular introduction to evolutionary biology for nonscientists (Charlesworth & Charlesworth 2003).

Deborah has also sat on the editorial boards of all of the main journals in evolutionary biology, including Molecular Ecology, and takes great care and effort in the handling of all studies that pass across her desk. She encourages careful, rigorous science, and scientific writing that is explicit about the strengths and weaknesses of studies. She avoids overstating results and is allergic to flashiness and the misuse of words. From my own experience working with Deborah, I will never again use the word ‘impact’ in my scientific writing (and have forced this on my co-authors) when I mean ‘effect’—a small point, but it highlights the value Deborah places on scientific accuracy over salesmanship. While she is sceptical of using new technologies for their own sake, her latest work exploiting Illumina sequencing to examine Y-chromosome degeneration highlights that when there are good reasons to adopt novel methods for a rigorous test of theory, she will lead the way in developing these new approaches. One of Deborah’s great accomplishments that she has passed on to her trainees and to the field is this necessity of fully integrating theory and empirical work, and her research career highlights a highly successful two-way interaction between them.

Stephen Wright

University of Toronto.

October 26th, 2011

I am grateful to Spencer Barrett for his photograph, discussion and comments on the text.