This study is directed toward finding the evolutionary roots of contemporary proteins, primarily by the computer-assisted comparison of available sequences. The study involves (a) the searching of a large protein sequence collection for potentially related sequences, (b) the computer alignment of possibly related sequences and (c) the application of empirical and statistical tests to find the likelihood that the proteins being studied have shared common ancestry. Phylogenetic trees will be constructed wherever appropriate. A high speed, large memory computer is essential for all of these aspects. The required computer programs are all on hand, as is a large protein sequence data base (NEWAT). All newly reported sequences are searched against the data base as they appear. The proteins to be studied fall into several groups. First there are those proteins """"""""unique"""""""" to vertebrates but which most likely have common ancestry with pre-vertebrate proteins. Examples are blood plasma proteins like albumin, fibrinogen, fibronectin, blood clotting proteins, ceruloplasmin, transferrin, the complement proteins and Alpha-2-macroglobulin. Many of these proteins have internally duplicated sequences that can serve as clues to the times of invention or divergence. These studies can shed considerable light on structure-function relationships by underlining which features of a protein have been most rigorously conserved during evolution. In addition to those proteins unique to vertebrates, some mainstream enzymes and ancient proteins thought to be essential to all living creatures will be studied. These include nucleic acid polymerases, tRNA synthetases and mainstream glycolytic enzymes. By using a battery of computer methods in combination we hope to be able to tease out resemblances that were not previously discernable.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034434-02
Application #
3285397
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Smith, M W; Doolittle, R F (1992) A comparison of evolutionary rates of the two major kinds of superoxide dismutase. J Mol Evol 34:175-84
Nagel, G M; Doolittle, R F (1991) Evolution and relatedness in two aminoacyl-tRNA synthetase families. Proc Natl Acad Sci U S A 88:8121-5
Seely Jr, O; Feng, D F; Smith, D W et al. (1990) Construction of a facsimile data set for large genome sequence analysis. Genomics 8:71-82
Doolittle, R F; Riley, M (1990) The amino-terminal sequence of lobster fibrinogen reveals common ancestry with vitellogenins. Biochem Biophys Res Commun 167:16-9
Doolittle, R F; Feng, D F; Anderson, K L et al. (1990) A naturally occurring horizontal gene transfer from a eukaryote to a prokaryote. J Mol Evol 31:383-8
Xu, X; Doolittle, R F (1990) Presence of a vertebrate fibrinogen-like sequence in an echinoderm. Proc Natl Acad Sci U S A 87:2097-101
Doolittle, R F; Feng, D F; Johnson, M S et al. (1989) Origins and evolutionary relationships of retroviruses. Q Rev Biol 64:1-30
McClure, M A; Johnson, M S; Feng, D F et al. (1988) Sequence comparisons of retroviral proteins: relative rates of change and general phylogeny. Proc Natl Acad Sci U S A 85:2469-73
Feng, D F; Doolittle, R F (1987) Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J Mol Evol 25:351-60
McClure, M A; Johnson, M S; Doolittle, R F (1987) Relocation of a protease-like gene segment between two retroviruses. Proc Natl Acad Sci U S A 84:2693-7

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