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The Genetics Society of America (GSA) Medal is awarded to an individual for outstanding contributions to the field of genetics in the past 15 years. Recipients of the GSA Medal are recognized for elegant and highly meaningful contributions to modern genetics and exemplify the ingenuity of GSA members. The 2015 recipient is Steven Henikoff, whose achievements include major contributions to Drosophila genetics and epigenetics, Arabidopsis genetics and epigenetics, population and evolutionary genetics, genomic technologies, computational biology, and transcription and chromatin biology. Among these achievements, Henikoff elucidated the mechanism for position-effect variegation, revealed a central role for variant histones in nucleosome assembly at active genes, and provided new insights into genome evolution. He has also developed widely used computational tools for genome and protein analysis and new strategies for mapping chromatin-binding sites.
Genetics was born with Gregor Mendel's classic paper (Mendel 1866), but it was A. H. Sturtevant's introduction of the firstgeneticmapin1913thatdefined the field of genetics as we know it today (Sturtevant 1913). For several decades, the genetic map was an ordering of genes along the chromosome determined by crossing over and chromosomal rearrangement. Beginning in the 1970s, restriction endonucleases allowed for genetic mapping to be based directly on DNA, which was eventually supplanted by DNA sequencing. As we enter the second century of genetic mapping, we are witnessing a progression from a genetic map defined by DNA sequence to a map enriched by the epigenomic landscape. Here I describe this latest transformation of the genetic map from the perspective of an observer and participant.
My interest in genetic maps began in the mid-1980s when I discovered a glaring exception to Sturtevant's linear order of genes along the chromosome: a pair of "nested genes," in which a Drosophila pupal cuticle protein is encoded within an intron of the Gart purine biosynthetic pathway gene encoded on the opposite strand (Henikoff et al. 1986). By then, traditional "forward" genetics based on a genetic map was giving way to "reverse" genetics, which begins with homology searching and ends with phenotypic analysis of a mutant. Much of our attention during the reverse-genetics era was focused on improving homology searches, leading to popular tools such as the BLOSUM series of amino acid substitution matrices (Henikoff and Henikoff 1992) and SIFT (Sorting...