Collaborative Research: The Role of Gene Duplication in the Evolution of Chordate Developmental Regulation

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0321470RuddleThe interconnection between development and evolution (Devo-Evo) was recognized in the mid-1800's by Darwin and Haeckel, though it has not been until very recently that the mechanistic basis for this crucial link has been readily addressable to experimental biology. In this collaborative project a question concerning the developmental evolution of the vertebrate bauplan is addressed: what are the developmental and evolutionary consequences of gen(om)e duplication during vertebrate phylogeny? It has been known for a long time that the evolution of the vertebrates was associated with a major expansion of genome size, either by gene or genome duplications. The present project focuses on the Hox gene clusters, a complex of genes that encode transcription factors known to be involved in a wide range of biological activities, including the development of the body axis, fins and limbs and many other organs. Vertebrates have the peculiar tendency to duplicate and retain Hox clusters, while no such tendency is apparent in invertebrates. It is not known why vertebrates have this tendency and whether these duplication events had an influence on the evolution of the vertebrate body plan. The goals of this project are to understand the extent and history of Hox cluster duplications among the vertebrates (specifically focusing on the teleosts), and to determine whether such duplications have facilitated evolutionary change both functionally and morphologically. We will use the ray finned fish radiation, in which the most recent Hox cluster duplication has been documented, as our experimental focus. The experimental approach involves: (1) tracing the patterns of molecular evolution of the Hox clusters and their genes, with the aim to determine whether the teleost Hox cluster duplication was coincident with the teleost radiation; (2) using Bacterial Artificial Chromosome technology and computational genomics methods in order to detect changes in the organization of clusters as well as identify changes in the pattern of non-coding sequence conservation; (3) employing BAC-reporter transgenesis as a comparative tool to draw inferences with respect to the effects of gene duplication on expression patterns; and (4) employing statistical tests to both coding and non-coding regions of Hox clusters to draw inferences with regard to the evolutionary forces (selection/drift) acting on duplicated genes and clusters. This investigation represents a part of an ongoing collaboration between three investigators of diverse backgrounds: Frank Ruddle (Yale University) has expertise in mammalian developmental biology, mouse transgenesis and homeobox genes; Gunter Wagner (Yale University) has an extensive background in quantitative-mathematical approaches to evolution and developmental evolution; and Chris Amemiya (formerly Boston University and now at Virginia Mason Research Center) has expertise in vertebrate zoology, genetics, and genomics. Each investigator is focussing on different aspects of the project but with the same overall goals in mind. This consortial approach has proven effective in the past and considerable progress has been made since the previous funding cycle. The broad impact of this proposal is measured in two ways: (1) by employing a highly interdisciplinary and novel approach for evaluating a complex problem in biology; and (2) by providing a wealth of research and educational resources. These training opportunities, including new summer traineeships for teachers and undergraduates of underrepresented minorities.