| 1. |
- Zhao, Yaofeng, et al.
(author)
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Ornithorhynchus anatinus (Platypus) Links the Evolution of Immunoglobulin Genes in Eutherian Mammals and Nonmammalian Tetrapods
- 2009
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 183:5, s. 3285-3293
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Journal article (peer-reviewed)abstract
- The evolutionary origins of mammalian immunoglobulin H chain isotypes (IgM, IgD, IgG, IgE, and IgA) are still incompletely understood as these isotypes differ considerably in structure and number from their counterparts in nonmammalian tetrapods. We report in this study that the platypus (Ornithorhynchus anatinus) Ig H chain constant region gene locus contains eight Ig encoding genes, which are arranged in an mu-delta-o-gamma 2-gamma 1-alpha 1-epsilon-alpha 2 order, spanning a total of similar to 200 kb DNA, encoding six distinct isotypes. The o (o for Ornithorhynchus) gene encodes a novel Ig H chain isotype that consists of four constant region domains and a hinge, and is structurally different from any of the five known mammalian Ig classes. This gene is phylogenetically related to nu (epsilon) and gamma, and thus appears to be a structural intermediate between these two genes. The platypus delta gene encodes ten heavy chain constant region domains, lacks a hinge region and is similar to IgD in amphibians and fish, but strikingly different from that in eutherian mammals. The platypus Ig H chain isotype repertoire thus shows a unique combination of genes that share similarity both to those of nonmammallian tetrapods and eutherian animals and demonstrates how phylogenetically informative species can be used to reconstruct the evolutionary history of functionally important genes.
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| 2. |
- Zhang, Ziding, et al.
(author)
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Potential for Dramatic Improvement in Sequence Alignment against Structures of Remote Homologous Proteins by Extracting Structural Information from Multiple Structure Alignment.
- 2003
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In: Journal of Molecular Biology. - 1089-8638. ; 332:1, s. 127-142
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Journal article (peer-reviewed)abstract
- A novel method has been developed for acquiring the correct alignment of a query sequence against remotely homologous proteins by extracting structural information from profiles of multiple structure alignment. A systematic search algorithm combined with a group of score functions based on sequence information and structural information has been introduced in this procedure. A limited number of top solutions (15,000) with high scores were selected as candidates for further examination. On a test-set comprising 301 proteins from 75 protein families with sequence identity less than 30%, the proportion of proteins with completely correct alignment as first candidate was improved to 39.8% by our method, whereas the typical performance of existing sequence-based alignment methods was only between 16.1% and 22.7%. Furthermore, multiple candidates for possible alignment were provided in our approach, which dramatically increased the possibility of finding correct alignment, such that completely correct alignments were found amongst the top-ranked 1000 candidates in 88.3% of the proteins. With the assistance of a sequence database, completely correct alignment solutions were achieved amongst the top 1000 candidates in 94.3% of the proteins. From such a limited number of candidates, it would become possible to identify more correct alignment using a more time-consuming but more powerful method with more detailed structural information, such as side-chain packing and energy minimization, etc. The results indicate that the novel alignment strategy could be helpful for extending the application of highly reliable methods for fold identification and homology modeling to a huge number of homologous proteins of low sequence similarity. Details of the methods, together with the results and implications for future development are presented.
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