 Section 3, Conservation Genetics. So far, we've largely focused on issues directly concerning humans. What about non-human genetic markers and non-human evolution? The field of conservation genetics is an interdisciplinary field of study that looks at how to conserve the diversity of life by understanding evolution and genetics. One of the principal areas of study is genetic diversity. Diversity is even more important than simple numbers when organisms begin to dwindle. A population that loses its diversity is very prone to disease, infant mortality, and rapid decline in population, even if its numbers are relatively high. For example, the giant panda is very near to extinction. We know that there are about 270 in captivity, but the wild populations have been harder to estimate. Based on computations of genetic diversity that were developed from evolutionary population genetics, it would appear that the panda population is not as endangered as once thought. The wild populations may be as high as 3,000 individuals, and the diversity is relatively high. The other important area is identifying which populations are actually distinct species or genetically divergent subgroups. While a fisherman may not be able to tell the difference between different types of salmon, a biologist using DNA technology and an understanding of evolutionary change can determine that a certain river is home to a rare and unique species of salmon that should be conserved. Section 4, Agriculture The other major application for non-human genetics and evolution might be agriculture. We are highly dependent on only a few crops for most of our food, and evolution can help us understand how to manage that delicate situation. The obvious use for evolution in agriculture is in understanding how to improve yields by artificial selection. Humans have been doing this type of manipulation since we were hunter-gatherers, harvesting and spreading the seeds of easy to pick and palatable wild crops. In the last 60 years, however, we have added new technologies to that selection. We can now map genomes, determine which genes control which traits, and carefully select the true breeding strains with the best yields, disease resistance and marketability. We can do all of this without introducing foreign DNA, simply from our understanding of inheritance with modification. The type of study is referred to as quantitative trait loci mapping, and it started the Green Revolution in crop development decades before modern transgenic techniques existed. As in conservation genetics, understanding evolution can aid us in maintaining adequate diversity in our crops, in detecting the spread of trans genes, or horizontally transferred genes from other plants, and to determine the true genetic identity of newly emerged strains. Evolutionary theory is used to understand selection pressures placed on plant pathogens like insects and blights, or weed plants that compete with crops. It can also help us to reconstruct the evolutionary history of a crop or livestock, so we can identify what genetic changes have occurred over time. Such studies on corn's closest relatives in central Mexico have identified ancestral strains with remarkable disease resistance. Similar studies on ancestral cow populations in South America have uncovered existing resistance genes to common cattle diseases. Crossbreeding efforts could secure a more hearty and resistant food source. Section 5, Gledistics and Reconstructing Philogenes One of the most striking evidences for evolution is the nested hierarchy. Organisms can be grouped on the basis of their genetic homology, and the resulting tree, or cladogram, matches up remarkably well with other lines of evidence. We also see common patterns of divergence. Organisms that are closely related will share the most sequence, but as we choose comparisons between organisms that diverged a much longer time ago, the homologies become weaker. There are some notable exceptions. Some sequences show large differences, some show very little difference. How should we explain this deviation from the expected substitution rates? The answer primarily is selection. Those gene products that are essential for basic functions in the organism do not change very much at all over time. Silent mutations, those that do not affect the function of the gene product, continue to accumulate, but few changes occur in the protein sequence because if they did, it would result in a decrease in fitness. We'll talk a bit more about this in the next section. The fields of bioinformatics and genomics focus on these types of analyses between the genomes of different organisms. What kind of applications can we find for bioinformatics, comparative genomics, and phylogenetics? Perhaps the most relevant is in the field of emerging diseases. Suppose tomorrow that a new illness began taking lives in southern Texas, primarily children and newborns. Hospital labs, state health agencies, and eventually national agencies like the CDC and U.S. Amrit would be on the scene looking for a cause. Suppose we culture out an unidentified bacteria from the lungs of very sick children in the region. What tools would we have to understand this new lethal pathogen? We'd sequence the DNA and we'd look at what conditions the bacteria likes the most, but without a knowledge of macroevolutionary change, we would be missing the most important tool of all. The ability to interrogate the new genome in relation to other well-characterized pathogens. Suppose in this case we find that this germ is very closely related to a pathogen of cattle, but with an inserted region that matches most closely the presence of a virus of bacteria. We would have valuable information about how to treat the disease and save children's lives, and how to manage the diseases spread. Going back to the idea of conservation genetics from section 3, one application of phylogenetics is in preserving near-extinct species. As an example, take the story of Lonesome George, the last known individual of the Penta Island tortoise, a subspecies of Galapagos tortoise. Poor George, believed to be around 80 years old, was believed to be the last of his kind, and with no female, we were facing the end of his subspecies. Then evolutionary biologists, using DNA technology, discovered a very closely related subspecies that appeared to have interbred with the Penta Island group in the recent past. Another individual of the same group was also discovered at the Prague Zoo, among other Galapagos tortoises. Unfortunately for George, it was another male. Current efforts are underway to see if George and the females from a related subspecies can create a hybrid offspring to preserve some of his genes. So far, they have been unsuccessful. So our understanding of how different groups of organisms are related to each other can benefit our stewardship of our planet, but it can also help to save human lives. Section 6, discovering genes in regulatory regions. Once the Human Genome Project had a fairly complete database of sequence, scientists had a very powerful tool available for the mapping of human genes. But how can they detect the important sequences, the ones that have the important function in the cell or organism? One very powerful approach is called selective sweeps. Selective sweeps compare the frequency of certain markers to their theoretically expected distribution in the absence of selection pressures. We also use comparisons of the same sequence between species. Certain regions will show a high amount of conservation. They don't change very much. Those are regions that are likely to have some function. The more highly conserved, the more likely those regions have some crucial role in the cell. For biologists, this was like a high-resolution pirate map of the Caribbean filled with Xs. There were so many exciting new genes to be discovered, and we knew exactly where many of them were. All that remained was to identify what they did. Even within a gene, looking at the DNA bases that are most highly conserved often tells us something about the active site of that gene product. This approach has led to a wealth of information about how genes are regulated by identifying regulatory and promoter regions. We've also learned a great deal about how genes are expressed by looking at the similarities and differences in how different animals develop as embryos. It's hard to pick out a specific example because all of modern molecular genetics is based on comparisons of genomes between widely ranging species. The other important concept in genetic analysis by macroevolution is the ability to use model organisms to stand in for humans. For ethical and safety reasons, we prefer not to experiment on humans. But when we use a non-human substitute for testing and analysis, we need to understand the differences produced by macroevolutionary change. This is real information we can't get from intelligent design or other creationist belief systems. Take the case of the Rouss Sarcoma virus in chickens. In 1911, Francis Rouss identified a retrovirus that could cause cancer in chickens, the Rouss Sarcoma virus, work which earned him the 1966 Nobel Prize in medicine. In 1979, Bishop Envarmus noticed that the retrovirus actually contained a defective version of a chicken gene. That chicken gene, now called SRC or Sark, is what is known as a proto-oncogene. The million-dollar question was whether humans would have the same gene, with the potential to cause cancer. Humans and chickens are separated by a great deal of evolution, but this gene plays such a crucial role we would expect it to be highly conserved. And in 1981, Varmus and Bishop, using their work on the chicken SRC gene, discovered the first human oncogene, earning them a 1989 Nobel, and leading to the development of a class of chemotherapeutics, the classic example of which is Gleavec.