DNA: past and future
Though both were first identified in his lifetime, Darwin knew nothing of DNA, or genes. The first few decades of the 20th century saw the fusion of genetics with evolution, and then with the double helix and the genetic code, the final pieces in the grand unifying theories of biology ultimately revealed a universal picture of life on Earth - a single, sprawling tree where every living thing going back four billion years was bound to each other through the transmission of DNA via cells. This unification, enabled by technology, has allowed two things, the first of which Darwin himself speculated about: we are close to modelling the singular origin of life itself. But what no-one predicted was that our mastery of DNA would create a set of tools, crafted by evolution, but assembled by us that will power the 21st century industrial revolution - synthetic biology.
Adam Rutherford
Editor for the science journal Nature
Darwinism in the modern scientific era: Mechanisms of response to novel and changing environments
Perhaps the most remarkable aspect of Darwin's thinking was his intuition about the importance of trait variation without knowledge of the molecular level mechanisms that produce that variation. Since Darwin's ideas were resolved with Mendel's work through the Modern Synthesis, researchers interested in adaptation have focused on DNA sequence variation, and the assumption that trait variation is ultimately based on DNA sequence differences. However, the research community now has abundant sequence information for a variety of organisms, but has still made little progress in understanding how the genome actually functions to create complex traits and adapt to complex environments. Recent studies increasingly demonstrate that other molecular events like the activity of transposable elements and epigenetic effects have tremendous power to drive genome function. Epigenetic effects like DNA methylation and histone modifications in particular can result in heritable, novel phenotypes even without variation in DNA sequence and could therefore provide an unappreciated source of response to environmental conditions. The implications of epigenetic effects for evolution are just beginning to be explored, but epigenetic variation may expand the ecological and evolutionary options of plant and animal species in the face of novel or rapidly changing environments.
Christina Richards, Ph.D.
University of South Florida, Department of Integrative Biology
Genetic and physiological adaptation in high-altitude Tibetans
Studies of native high-altitude residents, who have been challenged by decreased oxygen availability (hypoxia) for hundreds of generations, provide the unique opportunity to explore human adaptation. Previous research has shown that highland populations from different continents and non-native highlanders respond to altitude in different ways, yet a great deal remains to be learned about the mechanisms underlying this variation. Most humans living at altitudes above 4000 meters develop polycythemia (increased red blood cell production), classically considered an adaptive response to enhance oxygen transport at altitude. It is thus surprising to find that many healthy Tibetan highland natives are not polycythemic. Recent genomic analyses show that Tibetans have several genetic adaptations to high altitude and a few of these adaptive hypoxia-related genes are further associated with loss of polycythemia. In order to determine the physiological relevance and genetic underpinnings responsible for Tibetan adaptations, we are examining exercise capacity and oxygen transport, the precise genetic targets that afford evolutionary advantages, and the relationships among these factors and relatively lower hemoglobin levels (loss of polycythemia) in adapted Tibetans. This natural experiment in human adaptation has broad implications for understanding evolutionary processes and provides important insight into potential causes/effects of hypoxia-associated disease.
Tatum S. Simonson
University of California San Diego
Darwin and the Genomics Revolution
Our genomes house the genes that encode all the proteins made in our cells, as well as many other segments of DNA that control the expression of these genes. These regulatory DNA sequences determine the amounts of each protein that are synthesized, in which cells they are made, and when they are made during development and in response to the environment. A major goal of the Human Genome Project was to produce the complete DNA sequence of a single reference human genome, as well as sequences of the genomes of other organisms, and to make these data freely available to everyone. Since these initial goals were met, the technologies for DNA sequencing have made remarkable advances, so that many organisms' genome sequences, as well as those of many thousands of people from around the world, are now available. Comparison of human sequences with those of other organisms to pinpoint evolutionarily conserved segments has been an invaluable tool for identifying and characterizing the small portion of our genome that encodes proteins and regulatory DNA sequences. These comparisons, as well as very large-scale datasets of the read-out of the genomes, including complete RNA, DNA methylation, transcription factor occupancy and chromatin modfication and accessibility profiles, are being used to interpret the DNA sequences in our and other organisms' genomes. These approaches are transforming our understanding of basic biological processes, the etiologies and progression of diseases, and the development and application of new drugs and other treatments based on the fundamental causes rather than just the symptoms of diseases.
Richard Myers
President, Director and Faculty Investigator, HudsonAlpha Institute for Biotechnology