Actinomycetes are the single most important source of bioactive microbial products yet discovered. Although these bacteria are best known from soils, they can also be recovered from marine samples if the appropriate growth conditions are provided. The goals of this research were to gain a better understanding of marine actinomycete diversity, population genetics, and secondary metabolite production. The results have been interpreted using modern theories of prokaryotic genomics, speciation, and population biology. The research detailed herein is focused on marine actinomycetes belonging to the genus Salinispora as species within this taxon are proving to be model organisms with which to address fundamental questions about actinomycete biology. Chapter I provides an introduction to marine actinomycetes and the context within which the research described in subsequent chapters was performed. Chapter II presents a detailed study of the actinomycete diversity cultured from marine sediments collected around the island of Guam in the South Pacific. Chapter III explores the biogeographical distributions of the actinomycete genus Salinispora. Chapter IV is the result of the surprising discovery that Salinispora species produce secondary metabolites in a predictable, species-specific manner. This chapter includes a description of the patterns observed and the evolutionary implications of this finding. Chapter V provides a summary of the research performed and directions for future research in this field

Access to genome sequence data has challenged traditional natural product discovery paradigms by revealing that the products of most bacterial biosynthetic pathways have yet to be discovered. Despite the insight afforded by this technology, little is known about the diversity and distributions of natural product biosynthetic pathways among bacteria and how they evolve to generate structural diversity. Here we analyze genome sequence data derived from 75 strains of the marine actinomycete genus Salinispora for pathways associated with polyketide and nonribosomal peptide biosynthesis, the products of which account for some of today's most important medicines. The results reveal high levels of diversity, with a total of 124 pathways identified and 229 predicted with continued sequencing. Recent horizontal gene transfer accounts for the majority of pathways, which occur in only one or two strains. Acquired pathways are incorporated into genomic islands and are commonly exchanged within and between species. Acquisition and transfer events largely involve complete pathways, which subsequently evolve by gene gain, loss, and duplication followed by divergence. The exchange of similar pathway types at the precise chromosomal locations in different strains suggests that the mechanisms of integration include pathway-level homologous recombination. Despite extensive horizontal gene transfer there is clear evidence of species-level vertical inheritance, supporting the concept that secondary metabolites represent functional traits that help define Salinispora species. The plasticity of the Salinispora secondary metabolome provides an effective mechanism to maximize population-level secondary metabolite diversity while limiting the number of pathways maintained within any individual genome.