Current Research
Research in the lab is split between two main themes. First, we are interested in the evolution and maintenance of colour polymorphisms, and more generally, how they impact on the speciation and adaptive radiation of snails. This work is mostly being carried out on the charismatic European snail Cepaea and the endemic Japanese genus Mandarina. Second, we have initiated a BBSRC-funded programme to establish the pond snail Lymnaea stagnalis as a model for the understanding of the evolution and development of left-right asymmetry. The ultimate aim is to understand how chirality is determined at the molecular level, then extrapolate this to include the means by which variation in sequence, and dominance relations between alleles, contributes to the evolution of new chiral morphs. There are also a number of other projects - research on the conservation genetics of mustelids has been particularly fruitful because it links in to the Conservation Genetics course that I teach. Another avenue is to understand the function of the 'love' dart of snails.
A wide range of techniques are used, including the latest next generation DNA sequencing methods (454, Illumina, RAD sequencing), field work, mathematical models, phylogenetics and bioinformatics. Research therefore crosses several other sub-disciplines within the School, including Molecular Cell and Developmental Biology, Animal Behaviour and Ecology, and even Parasite Biology. We also benefit with strong links to Dr. Aziz Aboobaker in Nottingham, and collaborators in Edinburgh (Professor Mark Blaxter) and Japan (Professor Satoshi Chiba). Research in the lab is largely funded by BBSRC research grant, including the employment of a postdoc Maureen Liu, with smaller contributions from The Royal Society, the Japanese Society for the Promotion of Science, Daiwa Anglo Japanese foundation and the Genetics Society. RC.
Downloads of my publications are available from my website, www.angusdavison.org. PhD studentships are advertised on http://www.findaphd.com/
Unwinding snail chirality
For an organism to become asymmetric, bilateral symmetry must somehow be broken during development. Although multiple lines of enquiry remain, a deep-seated theoretical problem has stoked a burning interest in understanding the symmetry-breaking event - how is one side of an organism consistently distinguished from the other, given that the side that is called 'right' is essentially arbitrary? In the hypothetical view of Brown and Wolpert, the solution is provided by a pre-existing asymmetric molecular reference: an asymmetric gradient is created if an 'F-molecule' aligns with anterior-posterior and dorsal-ventral axes, so transporting an effector molecule towards the left or right. Asymmetry is thus entirely dependent upon the chirality (and subsequent alignment) of the F-molecule.
To attempt to validate the hypothesis, attention has focussed on the mouse, chick and zebrafish. In these model organisms, it has been found that rotational beating of cilia in the early gastrula creates an asymmetric extracellular fluid movement. It has therefore been argued that this is the symmetry-breaking step - the chirality of cilial motor proteins leads to directional fluid movement, ultimately determining the molecular and morphological asymmetry.
The unfortunate problem, however, is that a body of research indicates that the symmetry-breaking event sometimes occurs much earlier and at the intracellular level, preceding the commencement of ciliary movement. Together, the results suggest that in invertebrates and at least some vertebrates, molecular asymmetry is established early in embryogenesis, with morphological asymmetry only becoming apparent later. In consequence, the field of left-right patterning is "in disarray", because the notion that the rotary movement of cilia determine asymmetry is an elegant hypothesis that is undermined by earlier symmetry breaking events, even in some vertebrates. If the rotational beating of cilia is the symmetry-breaking step in the mouse, then it is probably the exception.
We are therefore developing the pond snail Lymnaea stagnalis as a lab animal to help understand the symmetry-breaking step, following years of neglect. The primary motivation for using Lymnaea is that molluscan asymmetry is established very early, and is genetically tractable; other "genome-era" molluscs do not vary in their chirality and so are of no direct use to this project.
The specific aim of a project that has been funded by the BBSRC is to utilise the power of ultrahigh-throughput DNA sequencing to directly clone the gene for chirality in Lymnaea stagnalis, working on the hypothesis that the maternal determinant of chirality in snail eggs is a molluscan F-molecule, or at least a molecule that interacts with it. With false positives excluded by genetic mapping, we will then attempt to definitively identify the gene with functional and cytological studies.
The general, long-term aim is put in place techniques that will in the future enable a precise understanding of the symmetry-breaking event in snails, stimulating investigative analyses of the same or related molecules in other organisms, including vertebrates. The work is timely because very recent technological advances have made identification of the asymmetry-determining locus feasible within the scale of a three year grant. Much of the work will be outsourced (e.g. sequencing, genotyping)
Some further background.The impetus for this project arose directly from work that I began while I was employed by the Royal Society in Edinburgh. During the fellowship, one of my research themes was to understand how sinistral coiling morphs of a land snail evolved, by comparing molecular phylogenies with morphological data and predictions based on a mathematical model. The results of the work were published in PLoS Biology, because the results suggest a general mechanism by which left-right asymmetry evolves in snails.
Since being employed by Nottingham, I have expanded my studies on snail chirality. An invited review on the biology of chiral snails stimulated my thoughts on the molecular mechanisms behind the establishment of asymmetry (Schilthuizen and Davison 2005), and with others I helped identify another explanation as to how asymmetry evolves: in some Malaysian snails, natural selection against new types is probably counteracted by sexual selection (Schilthuizen et al. 2007).
One problem with prior work on snail chirality has been a lack of cross-talk between disciplines and model organisms, so I would like to approach the problem from all angles. The aim now is to take my prior research on chirality to a logical conclusion, by bringing together a group of researchers that cover all the relevant disciplines. Having characterised the snail chirality locus, the ultimate aim is to understand how chirality is determined at the molecular level, then extrapolate this to include the means by which variation in sequence, and dominance relations between alleles, contributes to the evolution of new chiral morphs.
The work in PLoS Biology was widely reported in the press, including the popular science blog Pharyngula.
Left and right coiling Euhadra snails
Past Research
Sex and darts in slugs and snails
In the final stages of an elaborate courtship, many slugs and snails shoot calcareous 'love' darts into each other. While darts improve the reproductive success of the shooter, by promoting sperm survival in the recipient, it is unclear why some species have darts and others do not. In fact, dart use has barely been studied, except in the garden snail Cantareus aspersus (Helix aspersa). We took an evolutionary approach to attempt to understand the origin and use of darts (Davison et al 2005), by investigating mating behaviour in a wide range of species. 'Face-to-face' mating behaviour is restricted to three monophyletic groups of snails and slugs, and dart-bearing species are a subset within the same groups, which suggests a link, though not necessarily a causal one. As yet, we are unable to quantify the extent to which darts or mating behaviour, as well as several other correlated characters, are determined by common ancestry or regimes of natural or sexual selection, because our current phylogeny lacks resolution. However, the results emphasise that to understand the use of darts, then data are required from a wide range of species. The realisation that several characters are correlated may stimulate further research, and could eventually lead to some testable models for dart and mating behaviour evolution.
This work was featured in a report in the journal Trends in Ecology and Evolution.
Mating Trichotoxon heynemanni (Simroth, 1888), photographed in forest on the Shimba Hills, Kenya
Ancient origin of metazoan cellulase genes
While it is widely accepted that most animals do not have endogenous cellulases, relying instead on intestinal symbionts for cellulose digestion, the glycosyl hydrolase family 9 (GHF9) cellulases found in the genomes of termites, abalone and sea squirts could be an exception. Using information from expressed sequence tags, we showed that GHF9 genes are widespread in animals (Metazoa) (Davison and Blaxter 2005). We also demonstrated that eukaryotic GHF9 gene families are ancient, forming distinct monophyletic groups in plants and animals. As several intron positions are also conserved between four metazoan phyla then GHF9 genes must derive from an ancient ancestor.
This work was selected as a research highlight by the journal Nature (17 March 2005).
The diversity of GHF9 cellulases. This unrooted phylogram shows the topology supported by Bayesian analysis with a gamma correction. Metazoa, Viridiplantae, Fungi, Amoebozoa and Eubacteria are all monophyletic, with 100% support .Maximum likelihood and neighbour-joining analyses agree with this, albeit with lower bootstrap support, except that the maximum likelihood does not support a monophyletic fungal group. The base of the tree (shaded) is unresolved. Support using Bayesian / neighbor-joining / maximum likelihood methods is shown.
Future Research
Although I am always keen to hear from potential students, I am particularly keen to recruit a student that may wish to develop transgenic, in vitro injection or RNAi methods for Lymnaea stagnalis, with a view to further understanding chirality. Also, bioinformatics is another key area for future expansion, especially with a draft Lymnaea stagnalis genome in progress and a wealth of ESTs from various snail species.