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Biomedical subjects

Michael M Miyamoto

Publications and source records attributed to Michael M Miyamoto.

10 recordsLinked to original sources

Lamprey type II collagen and Sox9 reveal an ancient origin of the vertebrate collagenous skeleton.

Type II collagen is the major cartilage matrix protein in the jawed vertebrate skeleton. Lampreys and hagfishes, by contrast, are thought to have noncollagenous cartilage. This difference in skeletal structure has led to the hypothesis that the vertebrate common ancestor had a noncollagenous skeleton, with type II collagen becoming the predominant cartilage matrix protein after the divergence of jawless fish from the jawed vertebrates approximately 500 million years ago. Here we report that lampreys have two type II collagen (Col2alpha1) genes that are expressed during development of the cartilaginous skeleton. We also demonstrate that the adult lamprey skeleton is rich in Col2alpha1 protein. Furthermore, we have isolated a lamprey orthologue of Sox9, a direct transcriptional regulator of Col2alpha1 in jawed vertebrates, and show that it is coexpressed with both Col2alpha1 genes during skeletal development. These results reveal that the genetic pathway for chondrogenesis in lampreys and gnathostomes is conserved through the activation of cartilage matrix molecules and suggest that a collagenous skeleton evolved surprisingly early in vertebrate evolution.

Aging↗

Phylogeography of the salamander genus Pseudobranchus in the southeastern United States.

This study provides an extensive set of mitochondrial cytochrome b sequences for the salamander genus Pseudobranchus of the southeastern United States. These sequences were analysed by multiple phylogenetic methods that support a single set of major phylogeographic divisions for its two corroborated species (P. axanthus and P. striatus). These phylogeographic divisions overlap with the geographic breakpoints of other freshwater and terrestrial taxa in this region. Collectively, these overlapping patterns highlight the Central Highland and Tifton/Vidalia uplands as a significant barrier to Atlantic vs. Gulf coast groups, while reconfirming the phylogeographic significance of the Altamaha and Apalachicola river drainages. Despite their distinct phylogeographic split, P. striatus from west and east of these uplands are not currently recognizable as separate species according to the concordance principles for species definition.

Animals↗

Using equilibrium frequencies in models of sequence evolution.

BACKGROUND: The f factor is a new parameter for accommodating the influence of both the starting and ending states in the rate matrices of "generalized weighted frequencies" (+gwF) models for sequence evolution. In this study, we derive an expected value for f, starting from a nearly neutral model of weak selection, and then assess the biological interpretation of this factor with evolutionary simulations. RESULTS: An expected value of f = 0.5 (i.e., equal dependency on the starting and ending states) is derived for sequences that are evolving under the nearly neutral model of this study. However, this expectation is sensitive to violations of its underlying assumptions as illustrated with the evolutionary simulations. CONCLUSION: This study illustrates how selection, drift, and mutation at the population level can be linked to the rate matrices of models for sequence evolution to derive an expected value of f. However, as f is affected by a number of factors that limit its biological interpretation, this factor should normally be estimated as a free parameter rather than fixed a priori in a +gwF analysis.

Biological Evolution↗

Sequence alignments and pair hidden Markov models using evolutionary history.

This work presents a novel pairwise statistical alignment method based on an explicit evolutionary model of insertions and deletions (indels). Indel events of any length are possible according to a geometric distribution. The geometric distribution parameter, the indel rate, and the evolutionary time are all maximum likelihood estimated from the sequences being aligned. Probability calculations are done using a pair hidden Markov model (HMM) with transition probabilities calculated from the indel parameters. Equations for the transition probabilities make the pair HMM closely approximate the specified indel model. The method provides an optimal alignment, its likelihood, the likelihood of all possible alignments, and the reliability of individual alignment regions. Human alpha and beta-hemoglobin sequences are aligned, as an illustration of the potential utility of this pair HMM approach.

Algorithms↗

Evolutionary, structural and biochemical evidence for a new interaction site of the leptin obesity protein.

The Leptin protein is central to the regulation of energy metabolism in mammals. By integrating evolutionary, structural, and biochemical information, a surface segment, outside of its known receptor contacts, is predicted as a second interaction site that may help to further define its roles in energy balance and its functional differences between humans and other mammals.

Amino Acid Sequence↗

Using evolutionary rates to investigate protein functional divergence and conservation. A case study of the carbonic anhydrases.

Functional constraints on proteins limit their evolutionary rates at specific sites. These constraints allow for the interpretation of conserved residues and sites with a rate change as those most likely underlying the functional similarities and differences among protein subfamilies, respectively. This study describes new likelihood-ratio tests (LRTs) that complement existing ones for the identification of both conserved and rate change sites. These identifications are validated by the recovery of residues that are known from existing biochemical and structural information to be critical for the functional similarities and differences among carbonic anhydrases (CAs). In combination with this other information, these LRTs also support a unique antioxidant defense role for the puzzling CA III. As illustrated by the CAs, these LRTs, in combination with other biological evidence, offer a powerful and cost-effective approach for testing hypotheses, making predictions, and designing experiments in protein functional studies.

Amino Acid Sequence↗

Predicting functional divergence in protein evolution by site-specific rate shifts.

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.

Amino Acid Sequence↗

The role of medical libraries in undergraduate education: a case study in genetics.

Between 1996 and 2001, the Health Science Center Libraries and Department of Zoology at the University of Florida partnered to provide a cohesive and comprehensive learning experience to undergraduate students in PCB3063, "Genetics." During one semester each year, a librarian worked with up to 120 undergraduates, providing bibliographic and database instruction in the tools that practicing geneticists use (MEDLINE, GenBank, BLAST, etc.). Students learned to evaluate and synthesize the information that they retrieved, coupling it with information provided in classroom lectures, thus resulting in well-researched short papers on an assigned genetics topic. Exit surveys of students indicated that the majority found the library sessions and librarian's instruction to be useful. Responses also indicated that the project facilitated increased understanding of genetics concepts and appreciation for the scientific research process and the relevance of genetics to the real world. The library benefited from this partnership on a variety of fronts, including the development of skilled library users, pretrained future clientele, and increased visibility among campus research laboratories. The course and associated information instruction and assigned projects can be considered models for course-integrated instruction and the role of medical libraries in undergraduate education.

Computer-Assisted Instruction↗