Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “protein evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources

The analysis of a protein-polymorphism. Evolution of monomeric and homodimeric haemoglobins (erythrocruorins) of Chironomus thummi thummi (Insecta, Diptera).

The evolutionary history of 12 Chironomus thummi thummi (CTT) haemoglobins of known primary structures was reconstructed by the maximum parsimony method. This reconstruction demonstrates that the 12 CTT haemoglobin lineages originated monophyletically from a common ancestor within early Insecta and have the lineage to monomeric blood worm haemoglobin as their closest sister group. It can be further deduced that the earliest ancestral CTT haemoglobins were monomers and that a branch to all extant dimeric CTT haemoglobins emerged later in phylogeny near the base of Chironomidae, but perhaps still before Chironomus itself evolved. This ancient, pre-Chironomus history suggests that among insect taxa, now lacking expressed globins, remnants of globin genes might exist as unexpressed pseudogenes. By the parameter of base replacement frequencies, CTT haemoglobins appear as relatively slow-evolving proteins, showing a preponderance of guanine in equilibrium adenine transitions at the first nucleotide position of the codons but not at the second. The most conservatively-evolving amino acid positions are haem contacts; the next most conservative are in interhelical contacts and interior positions involved in stabilization of tertiary structure. Further elucidation of the phylogenetic origins and adaptive evolution of the multiple haemoglobins found in Chironomus will be possible by the maximum parsimony method once haemoglobins or, in their absence, haemoglobin pseudogenes are sequenced in species throughout Chironomidae and related taxa.

Amino Acid Sequence↗

Cotranscription and intergenic splicing of human galactose-1-phosphate uridylyltransferase and interleukin-11 receptor alpha-chain genes generate a fusion mRNA in normal cells. Implication for the production of multidomain proteins during evolution.

In the past 10 years, much attention has been focused on transcription preinitiation complex formation as a target for regulating gene expression, and other targets such as transcription termination complex assemblage have been less intensively investigated. We established the existence of poly(A) site choice and fusion splicing of two adjacent genes, galactose-1-phosphate uridylyltransferase (GALT) and interleukin-11 receptor alpha-chain (IL-11Ralpha), in normal human cells. This 16-kilobase (kb) transcription unit contains two promoters (the first one is constitutive, and the second one, 8 kb downstream, is highly regulated) and two cleavage/polyadenylation signals separated by 12 kb. The promoter from the GALT gene yields two mRNAs, a 1.4-kb mRNA encoding GALT and a 3-kb fusion mRNA when the first poly(A) site is spliced out and the second poly(A) is used. The 3-kb mRNA codes for a fusion protein of unknown function, containing part of the GALT protein and the entire IL-11Ralpha protein. The GALT promoter/IL-11Ralpha poly(A) transcript results from leaky termination and alternative splicing. This feature of RNA polymerase (pol) II transcription, which contrasts with efficient RNA pol I and pol III termination, may be involved, together with chromosome rearrangements, in the generation of fusion proteins with multiple domains and would have major evolutionary implications in terms of natural processes to generate novel proteins with common motifs. Our results, together with accumulation of genomic informations, will stimulate new considerations and experiments in gene expression studies.

Animals↗

Chloroplast small heat shock proteins: evidence for atypical evolution of an organelle-localized protein.

Knowledge of the origin and evolution of gene families is critical to our understanding of the evolution of protein function. To gain a detailed understanding of the evolution of the small heat shock proteins (sHSPs) in plants, we have examined the evolutionary history of the chloroplast (CP)-localized sHSPs. Previously, these nuclear-encoded CP proteins had been identified only from angiosperms. This study reveals the presence of the CP sHSPs in a moss, Funaria hygrometrica. Two clones for CP sHSPs were isolated from a F. hygrometrica heat shock cDNA library that represent two distinct CP sHSP genes. Our analysis of the CP sHSPs reveals unexpected evolutionary relationships and patterns of sequence conservation. Phylogenetic analysis of the CP sHSPs with other plant CP sHSPs and eukaryotic, archaeal, and bacterial sHSPs shows that the CP sHSPs are not closely related to the cyanobacterial sHSPs. Thus, they most likely evolved via gene duplication from a nuclear-encoded cytosolic sHSP and not via gene transfer from the CP endosymbiont. Previous sequence analysis had shown that all angiosperm CP sHSPs possess a methionine-rich region in the N-terminal domain. The primary sequence of this region is not highly conserved in the F. hygrometrica CP sHSPs. This lack of sequence conservation indicates that sometime in land plant evolution, after the divergence of mosses from the common ancestor of angiosperms but before the monocot-dicot divergence, there was a change in the selective constraints acting on the CP sHSPs.

Amino Acid Sequence↗

A transition probability model for amino acid substitutions from blocks.

Substitution matrices have been useful for sequence alignment and protein sequence comparisons. The BLOSUM series of matrices, which had been derived from a database of alignments of protein blocks, improved the accuracy of alignments previously obtained from the PAM-type matrices estimated from only closely related sequences. Although BLOSUM matrices are scoring matrices now widely used for protein sequence alignments, they do not describe an evolutionary model. BLOSUM matrices do not permit the estimation of the actual number of amino acid substitutions between sequences by correcting for multiple hits. The method presented here uses the Blocks database of protein alignments, along with the additivity of evolutionary distances, to approximate the amino acid substitution probabilities as a function of actual evolutionary distance. The PMB (Probability Matrix from Blocks) defines a new evolutionary model for protein evolution that can be used for evolutionary analyses of protein sequences. Our model is directly derived from, and thus compatible with, the BLOSUM matrices. The model has the additional advantage of being easily implemented.

Amino Acid Substitution↗

Catalytic antibodies: evolution of protein function in real time.

Natural selection of enzyme function has evolved over millions to billions of years, whereas antibody induction operates over a period of weeks. If one considers how new protein functions are generated, one sees that both the immune system and natural selection have powerful methods for the generation of diversity. In this treatise we discuss antibody catalysis from an evolutionary standpoint as we consider how the elicitation of a catalytic antibody can be a useful tool for exploring the nature of biological catalysis.

Amides↗

Genome dynamics, evolution, and protein modeling in the olfactory receptor gene superfamily.

The human olfactory subgenome represents several hundred olfactory receptor (OR) genes in a dozen or more clusters on several chromosomes. One OR gene cluster on human chromosome 17 has been characterized by us in detail. Based on a large-scale DNA sequence analysis, we have identified events of gene duplication and fusion as well as the generation of pseudogenes. The latter instances of 'gene death' could underlie the widespread phenomenon of human specific anosmias. Sixteen OR coding regions were found on this cluster, and six of them are pseudogenes. One of these pseudogenes, OR17-23, was found to be an intact open reading frame in an old world monkey. This may be a reflection of an OR repertoire diminution in man. A homology model of the OR protein was constructed by utilizing the rich information available on approximately 200 OR sequences. The putative odorant complementarity determining regions (CDR) was found to consist of 20 hypervariable residues facing an interior caving defined by transmembrane helices 3, 4 and 5. Such a model could be useful in analyzing additional OR gene sequences in the human genome in terms of odorant binding.

Base Sequence↗

Amino acid substitution during functionally constrained divergent evolution of protein sequences.

In aligning homologous protein sequences, it is generally assumed that amino acid substitutions subsequent in time occur independently of amino acid substitutions previous in time, i.e. that patterns of mutation are similar at low and high sequence divergence. This assumption is examined here and shown to be incorrect in an interesting way. Separate mutation matrices were constructed for aligned protein sequence pairs at divergences ranging from 5 to 100 PAM units (point accepted mutations per 100 aligned positions). From these, the corresponding log-odds (Dayhoff) matrices, normalized to 250 PAM units, were constructed. The matrices show that the genetic code influences accepted point mutations strongly at early stages of divergence, while the chemical properties of the side chains dominate at more advanced stages.

Amino Acid Sequence↗

Accuracy and power of statistical methods for detecting adaptive evolution in protein coding sequences and for identifying positively selected sites.

The parsimony method of Suzuki and Gojobori (1999) and the maximum likelihood method developed from the work of Nielsen and Yang (1998) are two widely used methods for detecting positive selection in homologous protein coding sequences. Both methods consider an excess of nonsynonymous (replacement) substitutions as evidence for positive selection. Previously published simulation studies comparing the performance of the two methods show contradictory results. Here we conduct a more thorough simulation study to cover and extend the parameter space used in previous studies. We also reanalyzed an HLA data set that was previously proposed to cause problems when analyzed using the maximum likelihood method. Our new simulations and a reanalysis of the HLA data demonstrate that the maximum likelihood method has good power and accuracy in detecting positive selection over a wide range of parameter values. Previous studies reporting poor performance of the method appear to be due to numerical problems in the optimization algorithms and did not reflect the true performance of the method. The parsimony method has a very low rate of false positives but very little power for detecting positive selection or identifying positively selected sites.

Algorithms↗

Molecular evolution of protein O-fucosyltransferase genes and splice variants.

O-Fucose has been described on both epidermal growth factor-like (EGF-like) repeats and Thrombospondin type 1 repeats (TSRs). The enzyme adding fucose to EGF-like repeats, protein O-fucosyltransferase 1 (Pofut1), is a soluble protein located in the lumen of endoplasmic reticulum (ER). A second protein O-fucosyltransferase, Pofut2, quite divergent from its homolog Pofut1, has recently been shown to O-fucosylate TSRs but not EGF-like repeats. To date, Pofut1 genes have only been characterized in human, mouse, and fly, and Pofut2 in mouse, fly, and partially in the nematode Caenorhabditis elegans. Here, we report cDNA sequences and genomic structures of bovine Pofut1 and Pofut2 genes and describe for the first time five alternative spliced transcripts for each gene. Only one transcript for both Pofut1 and Pofut2 encodes an active bovine O-fucosyltransferase. Variant transcript distribution was examined in 13 bovine tissues. Transcripts encoding active forms are ubiquitous, whereas other forms possess a more restricted tissue-expression profile. Sequence comparison and phylogenetic analyses revealed that both Pofut genes are present as a single copy in animal genomes, and their exon-intron organizations are conserved among vertebrates. The last common ancestor of all analyzed bilaterian species would be predicted to possess polyexonic Pofut genes in their genome.

Alternative Splicing↗

The nuclear lamins. A multigene family of proteins in evolution and differentiation.

The nuclear lamina consists of a proteinaceous layer or meshwork situated subjacent to the inner nuclear membrane. It is a karyoskeletal structure formed by a polymer containing one to three major polypeptides collectively termed the lamins. In all cells examined of vertebrates and invertebrates, the lamins exhibit very similar Mr ranging from 60 000 to 80 000. In vertebrates, two groups of lamins can be distinguished by their isoelectric value, one being near-neutral and the other acidic (isoelectric pH values of 5.6 and lower). The lamins represent a family of polypeptides with regions highly conserved during evolution. In certain species, e.g., the amphibian, Xenopus laevis, they exhibit cell type-specific expression during embryonic development, terminal differentiation of certain somatic cells, and gametogenesis. The nuclear lamina of diverse cell types can be composed of one, two or three different lamin polypeptides, without obvious differences in its morphology.

Animals↗

Yeast surface display for directed evolution of protein expression, affinity, and stability.

The described protocols enable thorough screening of polypeptide libraries with high confidence in the isolation of improved clones. It should be emphasized that the protocols have been fashioned for thoroughness, rather than speed. With library plasmid DNA in hand, the time to plated candidate yeast display mutants is typically 2-3 weeks. Each of the experimental approaches required for this method is fairly standard: yeast culture, immunofluorescent labeling, flow cytometry. Protocols that are more rapid could conceivably be developed by using solid substrate separations with magnetic beads, for instance. However, loss of the two-color normalization possible with flow cytometry would remove the quantitative advantage of the method. Yeast display complements existing polypeptide library methods and opens the possibility of examining extracellular eukaryotic proteins, an important class of proteins not generally amenable to yeast two-hybrid or phage display methodologies.

Amino Acid Sequence↗

A simple model for evolution of proteins towards the global minimum of free energy.

BACKGROUND: Proteins seem to have their native structure in a global minimum of free energy. No mechanism is known, however, for ensuring this property. Furthermore, computational complexity studies suggest that such a mechanism is not feasible. These seemingly contradictory observations can be reconciled by the suggestion that evolutionary selection can yield proteins whose native conformation is in the global minimum of free energy. The aim of this study is to investigate such evolutionary processes in a simple model of protein folding. RESULTS: Three possible evolutionary processes are explored.First, if the free energy of the chain is kept below a fixed threshold there is no improvement towards the global minimum. Second, if free energy is minimized directly, sequences emerge whose native conformation is in the global minimum of free energy. Third, when evolutionary pressure is applied within a small set of close homologs, sequences emerge whose functional conformation is in the global minimum of free energy. CONCLUSIONS: Although minimizing free energy does select for sequences whose functional conformation is in the global free energy minimum, we argue that for most proteins, which typically have free energy values of only 5-15 kcal/mol, such evolutionary pressure cannot be considered biologically plausible. In contrast, by repeatedly forcing sequences to avoid drifting towards competing "non-native" conformations, sequences emerge whose native conformation becomes very close to the global minimum of free energy. We argue that such a mechanism is both efficient and biologically plausible.

Algorithms↗

Differential evolution for protein crystallographic optimizations.

Genetic algorithms are powerful optimizers that have been underutilized in protein crystallography, given that many crystallographic problems have characteristics that would benefit from these algorithms: non-linearity, interdependent parameters and a complex function landscape. These functions have been implemented for real-space optimizations in a new fitting program, MIfit, for real-space refinement of protein models and heavy-atom searches. Some programming tips and examples will be presented here to aid others who might want to use genetic algorithms in their own work.

Algorithms↗