Proteins evolutionary pathways

Lichtarge, O., Sowa, M. E., and Philippi, A. (2002) Evolutionary traces of functional surfaces along G protein signaling pathway. Methods Enzymol. 344, 536-556. 

The sequencing of a- and /3-spectrin, a-actinin, and dystrophin has revealed similarities not only within the spectrin repeat, but also the other domains and motifs present within these proteins. Subsequent analyses have revealed an evolutionary pathway for the divergence of spectrin and dystrophin from a common a-actinin ancestor via a series of rearrangements, duplications, and evolution of repeats and other domains, as well as the acquisition of unique domains such as PH, WW, and SHS (Fig. 2). 

Tyagi N, Swapna LS, Mohanty S et al (2009) Evolutionary divergence of Plasmodium falciparum sequences, protein-protein interactions, pathways and processes. Infect Disord Drug Targets 9 257-271... 

With tree analysis it is possible to infer sequences of ancestral proteins and probable evolutionary pathways to their modern descendants.1 The advent of site-directed mutagenesis makes possible the recreation of evolutionary intermediates based on these predictions. One may then compare the properties of reconstructed intermediates with one another and with proteins from contemporary creatures. These comparisons provide a way of testing theories about the mechanism of molecular evolution. For example, this approach has provided a new criterion for distinguishing between neutral and nonneutral events.2 This chapter describes the use of site-directed mutagenesis to recreate ancestral lysozymes and presents methods of evaluating their properties. 

The bird lysozymes c, of which chicken egg white lysozyme (CL) is the most extensively studied example, provide an ideal system to recreate evolutionary intermediates and to study structure-function relationships of reconstructed ancestral proteins. Three major considerations qualify the avian lysozyme system for reconstruction of evolutionary pathways (1) the biochemistry of the enzymes has been extensively studied and well characterized,3,4 (2) there are many natural variants available from other birds, and homologous comparisons can be ensured since lysozymes for all game birds are encoded by a single gene,5 and (3) the three-dimensional structure of CL has been resolved at the atomic level, which allows for structural interpretation of the mutational impact.2,4 Proteins representing the ancestral, evolutionarily intermediate, and derived states of chicken and related bird lysozymes are made and characterized as described below. 

Fio. S. Scheme showing the two simplest evolutionary pathways leading from the ancestral protein with amino acid sequence AA to the derived protein with sequence BB. AB and BA represent sequences of the intermediates. 

Miyazaki K, Arnold FH (1999) Exploring nonnatural evolutionary pathways by saturation mutagenesis rapid improvement of protein function. J Mol Evol 49 716-720... 

Secretory protein translocation. See Stephenson, K Sec-dependent protein translocation across biological membranes. Evolutionary conservation of an essential protein transport pathway. Mol. Membrane Biol. 22,17-28, 2005. 

Comparison of sequences of the same protein in different species yields a wealth of information about evolutionary pathways. Genealogical relations between species can be inferred from sequence differences between their proteins. We can even estimate the time at which two evolutionary lines diverged, thanks to the clocklike nature of random mutations, For example, a comparison of serum albumins found in primates indicates that human beings and African apes diverged 5 million years ago, not 30 million years ago as was once thought. Sequence analyses have opened a new perspective on the fossil record and the pathway of human evolution. 

The observation that homology is often manifested as sequence similarity suggests that the evolutionary pathway relating the members of a family of proteins may be deduced by examination of sequence similarity. This approach is based on the notion that sequences that are more similar to one another have had less evolutionary time to diverge from one another than have sequences that are less similar. 

Cao TB, Saier MH Jr The general protein secretory pathway phylogenetic analyses leading to evolutionary conclusions. Biochim Biophys Acta 2003, 1609(1) 115-125. 

Available evidence supports a common ancestry for all cellulose synthases. These enzymes appear to have been a bacterial invention acquired by various eukaryotes via multiple lateral gene transfers. However, the proteins associated with regulation of cellulose biosynthesis and polymer crystallization seem to have evolved independently. Sequence divergence of eukaryotic cellulose synthases and the presence of multiple gene clusters associated with bacterial cellulose synthases are discussed in relation to the possible evolutionary pathways of cellulose biosynthesis. 

Laboratory e q>eriments were conducted to emulate die evolutionary pathway between triA and atzA, which may have occurred in nature by generating variants that were intermediate in sequence. Site directed mutagenesis was considered to be too cumbersome, over SOO different mutants would need to be made to cover the sequence space between AtzA and TriA. For this reason, DNA shuffling experiments (48) were conducted. DNA shuffling produces a combinatorial library of clones, generating proteins having one, two, or three amino acid differences fixim each parental proteia The clonal library is subsequently screened to discover one or more desirable properties in the new enzyme variants. In this exanqile, a small chemical library was screened to test the breadth of the substrate specificity of each clone. Included in die... 

The ability of proteins to bind prosthetic groups or cofactors and other proteins may have led to the development of enzymatic activity. Those proteins (e.g., hemoglobin, etc.) which have both nonenzymatic and enzymatic functions may represent one evolutionary pathway by... 

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