The Origin and History of Life on Earth
Evolutionary studies can help us to understand more about the history of life on earth. Different approaches are used to examine these questions depending on the timescales and the areas of interest (for example, questions about the origins of life versus the emergence of specific organs or specific adaptations).
Our work is broadly divided to study two different questions: What can evolution tell us about the origins of life on earth? What can evolution tell us about the origins of specific adaptations and how can we apply this experimentally or industrially?
The Early History of Life
The Temperature History of Life
Features of the physical environment surrounding an ancestral organism can be inferred by reconstructing sequences of ancient proteins made by those organisms, resurrecting these proteins in the laboratory, and measuring their properties. Our studies suggest that the ancestors of modern life were thermophiles (heat-loving). (NASA)
Inferring the palaeoenvironment of ancient bacteria on the basis of resurrected proteins
Gaucher, EA; Thomson, JM; Burgan, MF; Benner, SA
425 (6955) 285-288 (2003)
Features of the physical environment surrounding an ancestral organism can be inferred by reconstructing sequences(1-9) of ancient proteins made by those organisms, resurrecting these proteins in the laboratory, and measuring their properties. Here, we resurrect candidate sequences for elongation factors of the Tu family (EF-Tu) found at ancient nodes in the bacterial evolutionary tree, and measure their activities as a function of temperature. The ancient EF-Tu proteins have temperature optima of 55-65degreesC. This value seems to be robust with respect to uncertainties in the ancestral reconstruction. This suggests that the ancient bacteria that hosted these particular genes were thermophiles, and neither hyperthermophiles nor mesophiles. This conclusion can be compared and contrasted with inferences drawn from an analysis of the lengths of branches in trees joining proteins from contemporary bacteria(10), the distribution of thermophily in derived bacterial lineages(11), the inferred G+C content of ancient ribosomal RNA(12), and the geological record combined with assumptions concerning molecular clocks(13). The study illustrates the use of experimental palaeobiochemistry and assumptions about deep phylogenetic relationships between bacteria to explore the character of ancient life.
Developing biologically relevant models of sequence evolution and coupling these with structural and molecular biology to identify sites that are likely to be involved in changing function within a gene family is required to understand molecular function/behavior. Our studies highlight the importance of this method to identify unique protein binding domains and extract information related to divergent evolution.
Predicting functional divergence in protein evolution by site-specific rate shifts
Gaucher, EA; Gu, X; Miyamoto, MM; Benner, SA
Trends Biochem. Sci.
27 (6) 315-321 (2002)
Most modern tools that analyze protein evolution allow individual sites to mutate at constant rates over the history of the protein family. However, Walter Fitch observed in the 1970s that, if a protein changes its function, the mutability of individual sites might also change. This observation is captured in the 'non-homogeneous gamma model', which extracts functional information from gene families by examining the different rates at which individual sites evolve. This model has recently been coupled with structural and molecular biology to identify sites that are likely to be involved in changing function within the gene family. Applying this to multiple gene families highlights the widespread divergence of functional behavior among proteins to generate paralogs and orthologs.
The Evolutionary History of Specific Adaptations
The origins of fermentation
We exploited techniques in paleobiochemistry to resurrect enzymes involved in alcohol fermentation to understand the relationship of fermentable fruit and yeast in the age of the Dinosaurs. Our results help to connect the chemical behavior of these enzymes through systems analysis to a time of global ecosystem change, and highlights the utility of 'planetary systems biology'. (NASA)
Resurrecting ancestral alcohol dehydrogenases from yeast
Thomson, JM; Gaucher, EA; Burgan, MF; De Kee, DW; Li, T; Aris, JP; Benner, SA
37 (6) 630-635 (2005)
Modern yeast living in fleshy fruits rapidly convert sugars into bult ethanol through pyruvate. Pyruvate loses carbon dioxide to become acetaldehyde, which is reduced by alcohol dehydrogenase 1 (Adh1) to ethanol, which accumulates. Yeast later consumes the accumulated ethanol, exploiting Adh2, an Adh1 homolog differing by 24 (of 348) amino acids. Because many microorganisms cannot grow in ethanol, accumulated ethanol may help yeast defend resources in the fruit. We report here the reconstruction of the last common ancestor of Adh1 and Adh2, called AdhA. The kinetic behavior of AdhA suggests that it was optimized to make (not consume) ethanol. This is consistent with the hypothesis that before the Adh1-Adh2 duplication, yeast did not accumulate ethanol for later consumption but rather used AdhA to recycle NADH generated in the glycolytic pathway. Silent nucleotide dating suggests that the Adh1-Adh2 duplication occurred near the time of duplication of several other proteins involved in the accumulation of ethanol, possibly in the Cretaceous age when fleshy fruits arose. These results help to connect the chemical behavior of these enzymes through systems analysis to a time of global ecosystem change, a small but useful step towards a planetary systems biology.
Adaptations of aromatase in pigs
Joining a model for the molecular evolution of a protein family to the paleontological and geological records, and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy was adopted to understand reproductive strategies during mammalian speciation events. (NIH)
The planetary biology of cytochrome P450 aromatases
Gaucher, EA; Graddy, LG; Li, T; Simmen, RC; Simmen, FA; Schreiber, DR; Liberles, DA; Janis, CM; Benner, SA
2 (1) 19 (2004)
BACKGROUND: Joining a model for the molecular evolution of a protein family to the paleontological and geological records (geobiology), and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy expands systems biology to a planetary context, necessary for a notion of fitness to underlie (as it must) any discussion of function within a biomolecular system.
RESULTS: Here, we report an example of such an expansion, where tools from planetary biology were used to analyze three genes from the pig Sus scrofa that encode cytochrome P450 aromatases-enzymes that convert androgens into estrogens. The evolutionary history of the vertebrate aromatase gene family was reconstructed. Transition redundant exchange silent substitution metrics were used to interpolate dates for the divergence of family members, the paleontological record was consulted to identify changes in physiology that correlated in time with the change in molecular behavior, and new aromatase sequences from peccary were obtained. Metrics that detect changing function in proteins were then applied, including KA/KS values and those that exploit structural biology. These identified specific amino acid replacements that were associated with changing substrate and product specificity during the time of presumed adaptive change. The combined analysis suggests that aromatase paralogs arose in pigs as a result of selection for Suoidea with larger litters than their ancestors, and permitted the Suoidea to survive the global climatic trauma that began in the Eocene.
CONCLUSIONS: This combination of bioinformatics analysis, molecular evolution, paleontology, cladistics, global climatology, structural biology, and organic chemistry serves as a paradigm in planetary biology. As the geological, paleontological, and genomic records improve, this approach should become widely useful to make systems biology statements about high-level function for biomolecular systems.
The early history of life: Environment, building blocks and core cellular machinery
Recent evolutionary history: The origin and adaptation of specific traits