Analysis of Barry Hall\u27s Research of the E. coli ebg Operon: Understanding the Implications for Bacterial Adaptation to Adverse Environments

Much research has been done on the ebg operon of the bacterium Escherichia coli over the last 30 years. Although the function of the ebg operon is still unknown, it has been observed that specific mutations within this operon enable the bacterium to metabolize lactose sufficiently to allow growth. Interestingly, this growth occurs in a lacZ- genotype (gene for β-galactosidase in the lac operon). Thus, this gene has been referred to as an “evolved β-galactosidase,” and has been widely accepted as an example of “evolution in action.” Under these cultivation conditions, the ebg operon appears to harbor adaptive mutations. Mutations (at codons 92 and 977) in the ebgA gene (which codes for ebg β-galactosidase) occur consistently when an E. coli lacZ- population undergoes carbon starvation in the presence of lactose. These are the only mutations observed in the ebgA gene and these particular mutations are not found when the bacteria are subjected to different adverse environmental conditions. Mutations are also found in other genes suggesting a mechanism which has affects on the entire genome. Several models have been proposed to explain this phenomenon. Hall’s work needs critical evaluation. Mutations in the Ebg system are clearly not an example of evolution but mutation and natural selection allowing for adaptation to the environment. Several possibilities for the function of the Ebg system are suggested. In addition, there is an assessment of the likelihood of these mutations in the ebg operon occurring in a natural setting. An implication of this research is an understanding that adaptive mutation makes “limited” changes which severely restrict its use as a mechanism for evolution. Adaptive mutations can readily fit within a creation model where adaptive mechanisms are a designed feature of bacteria. Further understanding of these mutations in the ebg operon may help the development of a creation model for adaptation of bacterial populations in response to the adverse environmental conditions in a post-Fall, post-Flood world

A Creationist Perspective of Beneficial Mutations in Bacteria

Mutations alter the nucleotide sequence of the DNA. They may affect the organism’s phenotype, which can play a key role in bacterial adaptation and transformation to changing environments. Some of these mutations even appear to be beneficial to the organism. However, creationists have tended to offer an inconsistent or incomplete perspective of “beneficial mutations” within a creation framework. This includes the frequent denial that mutations can ever provide a beneficial phenotype, and the concept that “beneficial mutations” are merely an evolutionist exaggeration. In bacteria, a wide range of mutations can be shown to provide a beneficial phenotype to the cell. These benefits are often of sufficient phenotypic affect that they can undergo strong positive selection. But, the benefits are generally temporary and limited. Some common examples of beneficial mutations are those involved in bacterial antibiotic resistance. These mutations potentially enable the bacterium to survive exposure to various antibiotics, but the resistance results from loss or reduction of pre-existing activities such as enzymatic, regulatory, or transport systems. Bacteria also can undergo adaptive mutation; a phenomenon used by bacteria to survive very specific stressful conditions. The exact mechanism is controversial because some results suggest a directed mutation specifically enabling adaptation to the environment, but at a mutation rate higher than random mutations would produce. Various mutations have also been found that enable bacteria to survive temporary exposure to high temperatures or starvation. Such mutations usually involve loss of certain sigma factors, reduction of DNA repair, or loss of specific regulatory controls. Other examples include several subpopulations of mutant strains of bacteria obtained over a period of up to 20,000 generations. These mutants have a greater “fitness” than the wild-type strain. However, analysis showed that most contained deletion mutations in various genes. Each of these examples, as well as numerous others, involves certain environmental conditions that make these mutations phenotypically beneficial. However, these mutations frequently eliminate or reduce pre-existing cellular systems and functions. This has been referred to as antagonistic pleiotropy; meaning the cell experiences a trade-off where a temporary benefit for surviving one environmental condition is provided at the expense of systems used for other environments. If the environmental conditions change, the mutation usually becomes less beneficial and perhaps even detrimental. Hence, these mutations do not provide a genetic mechanism that accounts for the origin of biological systems or functions. Rather, they require the prior existence of the targeted cellular systems. As such, beneficial mutations of bacteria fit concisely within a creation model where (a) biological systems and functions were fully formed at creation, (b) subsequent mutations can provide conditional benefits that enable the organism to survive harsh post-Fall conditions even though the mutation is generally degenerative, and (c) most bacteria need the ability to rapidly adapt to ever changing environments and food sources

Survey of Microbial Composition and Mechanisms of Living Stromatolites of the Bahamas and Australia: Developing Criteria to Determine the Biogenicity of Fossil Stromatolites

A stromatolite is typically defined as a laminated and lithified structure that is the result of microbial activity over the course of time. Fossil stromatolites are relatively abundant; however, modern living stromatolites are rare. Two well-studied examples of living stromatolites include those found in the Exuma Cays of the Bahamas and Shark Bay in Australia. Depending on dominant chemical reactions by bacteria and environmental conditions, accretion and lithification of the stromatolite occurs at intervals. Each layer or lamina of a stromatolite represents a former surface mat of bacteria. As long as cyanobacteria (or other phototrophs) colonize the top surface of the stromatolite, growth is likely to continue. Understanding microbial composition and mechanisms of living stromatolites is crucial to determining the biogenicity of fossil stromatolites. Although there is a paucity of fossilized bacteria in fossil stromatolites, their structural features closely resemble those of living stromatolites. A set of criteria from the study of living and fossil stromatolites has been developed to aid determination of the biogenicity of fossil stromatolites. It was concluded that there is now sufficient evidence for the biogenicity of many stromatolites, even as early as 3.5 Ga, so these need to be understood within the biblical framework of earth history. Discernment of genuine stromatolites in the geologic record may help determine boundaries between Creation Week, pre- Flood and Flood strata. In addition, understanding how various living stromatolites form in different environments provides insight into the pre-Flood environments in which fossil stromatolites grew

The microphthalmia transcription factor regulates expression of the tartrate resistant acid phosphatase gene during terminal differentiation of osteoclasts

The defective terminal differentiation of osteoclasts in mice homozygous for the mi allele of the microphthalmia transcription factor (MITF) gene implies that MITF plays a critical role in regulating gene expression during osteoclast ontogeny. To begin addressing the role of this transcription factor in the osteoclast, target genes need to be identified. In the present work, several lines of evidence show that the gene encoding the enzyme tartrate-resistant acid phosphatase (TRAP) is a target of MITE. Analysis of osteoclasts in vivo in the embryonic forelimb showed that MITF and TRAP RNA were coexpressed in a dynamic pattern during the process of endochondral ossification of long bone. Primary osteoclast-like cells (OCLs) produced from mi/mi mutant mice expressed TRAP messenger RNA (mRNA) at 8-fold lower levels than in OCLs derived from normal mice, indicating a direct link between MITF function and TRAP expression. The activity of mouse TRAP promoter-reporter genes was assayed in the primary OCLS by DNA-mediated transfection, and this activity was shown to depend on a conserved sequence (GGTCATGTGAG) located in the proximal promoter. Recombinant MITF protein recognized specifically this conserved sequence element. Expression of a TRAP promoter-green fluorescent protein (GFP) transgene mimicked the expression of the endogenous TRAP gene during differentiation of osteoclast-like cells, and the expression of the transgene was decreased 8-fold when placed into the mutant mi/mi background. These results are consistent with a role for MITF in gene expression during terminal differentiation of the osteoclast and will allow osteoclast-specific mechanisms of gene regulation to be studied in greater detail

Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer