Organogenesis in deep time: A problem in genomics,development, and paleontology

The fossil record is a unique repository of information on major morphological transitions. Increasingly, developmental, embryological, and functional genomic approaches have also conspired to reveal evolutionary trajectory of phenotypic shifts. Here, we use the vertebrate appendage to demonstrate how these disciplines can mutually reinforce each other to facilitate the generation and testing of hypotheses of morphological evolution. We discuss classical theories on the origins of paired fins, recent data on regulatory modulations of fish fins and tetrapod limbs, and case studies exploring the mechanisms of digit loss in tetrapods. We envision an era of research in which the deep history of morphological evolution can be revealed by integrating fossils of transitional forms with direct experimentation in the laboratory via genome manipulation, thereby shedding light on the relationship between genes, developmental processes, and the evolving phenotype.Paleontologists in recent decades have discovered a host of new taxa that reveal transitional stages in the evolution of birds, whales, mammals, tetrapods, frogs, salamanders, and arthropods (1–9). This pulse of discovery is not an accident, but the result of an elaboration of our ability to identify likely sites for fossil recovery by using increasingly refined phylogenies, stratigraphic maps, and geological records. Likewise, imaging techniques, such as high-energy CT, have opened up old and understudied fossil collections as new vehicles for discovery. With advances in both fieldwork and imaging, the discovery of the phenotypic basis for morphological innovation is at a critical moment in its long history: Novel perspectives on classical questions of anatomical evolution are within our reach.Fossils, when placed in a phylogenetic context, can reveal taxa with novel combinations of characters that could not be predicted by studying extant creatures alone. If we lacked fossil evidence of mammal-like reptiles, for example, then the physiological and morphological similarities of birds and mammals would likely be interpreted as homologies rather than examples of parallel evolution (e.g., the discredited “Haemothermia” clade) (10, 11). In addition to identifying solid taxonomic groupings, these same fossils reveal transitional series in the origin of the mammalian dentition, ear, and cranium (3). Our understanding of numerous other transformations, from the origin of birds to the origin of tetrapods, is seriously limited without the knowledge of extinct stem taxa.A rich fossil record permits us to document robustly supported transformation series in the evolution of an anatomical feature, organ system, or body plan. However, to understand the pattern and process of evolutionary transitions, paleontologists have increasingly turned their attention to development. In recent years, the combination of technologies from developmental biology and abundant genomic resources for a multitude of model and nonmodel organisms has greatly enriched our understanding of the genetic and developmental processes underlying organogenesis. This broad set of tools provides a new framework for testing hypotheses derived from paleontological findings, thereby forming an interdisciplinary research program with comparative genomics as well as genetic manipulation of embryonic development (12–15).Here, we use the evolution and diversification of the vertebrate limb as an exemplar to reveal how discoveries in paleontology can leverage experimental and comparative work in molecular biology, genomics, and embryology. First, we review how fossil analyses of early gnathostomes, coupled with embryological studies, offer the foundation for hypotheses on the origin of paired appendages. Then, we discuss current research on model and nonmodel species that shed light on the origin of digits by comparing gene expression and regulatory mechanisms underlying fin and limb development. Next, we examine recent studies that identify the genetic and developmental basis for digit reduction in tetrapods. Finally, we highlight novel technologies that are enabling biologists to solve century-old evolutionary puzzles with state-of-the-art molecular approaches. The synthesis of modern technology with paleontological findings has been an ongoing topic of interest (16–18). Continued advances in technology now give morphologists an ever-expanding toolkit to test genome function and, ultimately, manipulate genomes in a phylogenetic framework. When these new technologies are coupled with paleontological discovery, new insights into classical questions in evolutionary morphology lie in the offing.