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Newsletter Dec-Jan 2010 ISSN 1359-9321 The Galton Institute NEWSLETTER Galtonia candicans Issue Number 72 December 2009 from species destined to diverge could not Contents pair with each other at meiosis. He The Galton Institute believed this ‘accent’ resided in the percent differences in G-C content of the The Galton Institute Annual Annual Conference genome of horse and ass. A later speaker Conference 2009 1 st contested this view of hybrid sterility; that October 1 , 2009 it may be more due to gene sequences British Society for Population coding for ligand-receptor interactions, William Bateson: Studies Annual Conference enzymes, transport proteins etc being 2009 3 His exceptions and Origin of sufficiently different between horse and ass, particularly with regard to gonadal Species Revisited The Origins of Percussive development, that leads to hybrid sterility. Technology: a Smashing Time Professor Sir Walter Bodmer started in Cambridge 6 The 45th Annual Conference of the from the problem that Darwin’s ideas on Galton Institute was held on 1st October, the mechanism of inheritance were The Darwinian Renaissance in 2009 at The Royal Society and was inconsistent with his theory of evolution the Humanities and Social entitled William Bateson: His exceptions by Natural Selection. Mendel’s paper of Sciences 7 and origin of species revisited. This is a 1866 had a well developed set of alge- short report of the proceedings of the day. braic expressions accounting for his Why Aren’t the Social hybridization and segregation data Sciences Darwinian? 8 Professor Donald Forsdyke started producing a type of variation that Natural with the report of 1902 to The Royal Selection could work on. Mendel’s work Fertility declines in the past, Society where Bateson promulgated the was taken up by G E Hardy (1908) who Mendelian view of inheritance. Bateson’s proposed that Mendelian variants in a present and future: what we report intensified the fierce debate random mating population without other don’t know and what we need between the biometricians, led by Karl interfering factors would reach equilib- to know 9 Pearson, and the Mendelians. The lecturer rium in one generation. This later led to then considered Bateson’s contribution to test for the Hardy-Weinberg equilibrium Richard Soloway 12 speciation theory and suggested from the in population genetics. R A Fisher, a Published by: work of George Romanes, that reproduc- founding father of population genetics The Galton Institute tive isolation would need to precede (together with Haldane and Sewell 19 Northfields Prospect Natural Selection for species to evolve. Wright), demonstrated how blending Darwin considered Natural Selection as inheritance could be explained by the Northfields the prime factor in speciation. Professor inheritance of a few Mendelian factors LONDON SW18 1PE Forsdyke then discussed the Darwin working together. Bateson appeared to Telephone: 020-8874 7257 lecture given by Bateson in 1909 and lack the mathematical abilities to appreci- General Secretary: gave his own original and provocative ate Fisher’s contribution to the contro- Mrs Betty Nixon views on the cause of hybrid sterility. He versy of the Biometricians versus the took the case of the union of horse with Mendelians. Fisher also proposed the use Newsletter Editor: ass to produce the sterile mule. He of linkage studies for the prognosis of Robert Cohen believed that DNA sequences have an hereditary ailments in a paper as early as Web site: ‘accent’, rather like the different accents 1935; this was the dawn of the use of www.galtoninstitute.org.uk in speech, so that eventually the DNA polymorphic gene markers to attempt to GALTON INSTITUTE NEWSLETTER 1 DECEMBER 2009 trace ‘disease’ alleles. The subject Professor Dover considers these networks major contributions that Bateson had started with the use of the ABO blood to be the equivalent of Bateson’s made. Bateson’s large book on Materials groups, then moved to the HLA system, ‘motions’ and ‘harmonics’. During for the Study of Variation was published and latterly to the use of DNA polymor- ontogeny individuals have to construct in 1894, that is six years before the re- phisms. The early success of linking their own networks anew. A theory of discovery of Mendel and the importance HLA B27 to ankylosing spondylitis with evolution also requires theory of molecu- of discrete variation was recognised. an Odds Ratio of 158 was a great lar interactions (epistasis). He then gave Bateson strongly promoted Mendel’s stimulus to the field. Solomon and one practical example that this reviewer views on inheritance in British academic Bodmer made the very interesting did not fully understand, so an interested circles and applied it to human disease suggestion in the Lancet (1979) that the reader should refer directly to Professor through a suggestion he made to A E newly described DNA polymorphisms Dover’s publications. Garrod. Bateson later put forward the have the potential to cover the whole idea of linkage (which he called gametic Professor Sir David Baulcombe genome and so detect any of the genes coupling). He coined the term epistasis opened his Galton Lecture 2009 by involved in the inheritance of disease – a where two or more genes interact. He showing how the study of plants has prediction that has come true. The also coined the terms homeosis and benefited our understanding of the basic lecture ended by noting that very rare meristic variation where he considered structure and genetics of all living variants have been detected by a straight there to be a ‘master’ locus affecting organisms. Beginning with van Leeu- forward Mendelian analysis, and com- bodily structures and repetitive elements wenhoek’s microscopic studies of plants, mon variants by association with DNA in development, giving examples such as showing that they are made up of cells, to polymorphisms, so that it was now time polydactyly. Mendel’s discoveries of particulate to identify variants of frequency between genetics in the garden pea, to Barbara very rare and common that may have a Professor Cox then went on to elabo- McClintock’s discovery of transposons in large impact on disease expression. Sir rate each of these concepts. He gave a maize and to the infection of plants by Walter illustrated this with a histogram of very lucid and helpful account of the viruses such as the tobacco mosaic virus. the Odds Ratios of the genetic compo- inborn errors of metabolism that Garrod Studies of the latter have led to the nents of Type 1 Diabetes showing the first described, and noted that more than discovery of a unique mechanism of HLA system having the greatest impact, 2,000 ‘single-gene defects’ have been resistance to viral infection in plants. then variation of the insulin gene, grading documented. He then gave examples of This involves the plant genome making down to the right hand tail of genes that epistasis, taking as one example amongst an antisense RNA to target the sense are common but with a minor impact. others, a single mutation at the cystic RNA of the infecting virus and so Variants lying between the two clusters fibrosis locus giving rise to five different neutralising it. It is a type of ‘immune’ now need to be identified. phenotypes depending on the interaction mechanism whereby the plant gets with ‘background’ genes at other loci. He specificity from the invading virus to Professor Gabriel Dover enlarged on then went on to a detailed account of make a small double-stranded antisense one of Bateson’s ideas that variation homeotic mutations. The Hox genes RNA. This is cleaved by dicer enzymes comprised not only in the structure of regulate developmental events and were to single strands for combination with the material but also in the arrangement or first described in drosophilia where invading viral RNA. ‘motion’ or ‘harmonics’ of the material. mutations cause gross bodily defects such This led to Professor Dover’s views on as bithorax and antennapaedia – as first There are about 5000 genes in the plant epistasis of being two types: 1. genetic shown in Bateson’s early work, Materials genome that make small RNAs not only interaction fixed by evolutionary proc- for the Study of Variation (1894). He as a defence mechanism but also to esses i.e. co-adaptation; or 2. liberating gave many examples in humans such as regulate gene expression and integrate interactions or combinatorial flexibility. mutations in the Hox d13 genes cause gene function in epistatic interactions. Professor Dover pointed out that there polydactyly. He then dealt with the Some siRNAs may operate at the level of were many non-Mendelian interactions of intracellular signalling pathways involv- DNA promoters either to switch on or off DNA leading to flexibility such as ing the Hedgehog proteins which act as gene transcription. There is also evi- unequal crossing-over, gene conversion, morphogens and require sterols for their dence for uniparental expression of slippage, copy number variation, imprint- full functional activity. They direct siRNAs, for example the maternal ing etc. He then went on to describe embryonic development into different genome can suppress the paternal various combinatorial regulatory net- body parts and are conserved from flies genome. Professor Baulcombe then works using the mathematics of topology. to humans. Sonic Hedgehog is the one showed how this work in plants has been In the simplest terms a single gene can most studied in mammals and is active extended to non-Mendelian types of interact with a variety of networks critically during early human develop- inheritance in the mouse. (pleiotropy); or different genes can ment. Disruption of the pathway in interact with a single network (epistasis). Professor Timothy Cox first listed the humans can produce grotesque mal- DECEMBER 2009 2 GALTON INSTITUTE NEWSLETTER formations of the skull and brain, such as tion was the substrate for Natural Selec- acquired new Hox genes, possibly by holoprosencephaly – an extreme exam- tion he assembled a vast array of all the gene duplication, perhaps in its need for ple of which was cyclopia.
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