Functional Divergence (functional + divergence)

Distribution by Scientific Domains


Selected Abstracts


Comparative genomics and the study of evolution by natural selection

MOLECULAR ECOLOGY, Issue 21 2008
HANS ELLEGREN
Abstract Genomics profoundly affects most areas of biology, including ecology and evolutionary biology. By examining genome sequences from multiple species, comparative genomics offers new insight into genome evolution and the way natural selection moulds DNA sequence evolution. Functional divergence, as manifested in the accumulation of nonsynonymous substitutions in protein-coding genes, differs among lineages in a manner seemingly related to population size. For example, the ratio of nonsynonymous to synonymous substitution (dN/dS) is higher in apes than in rodents, compatible with Ohta's nearly neutral theory of molecular evolution, which suggests that the fixation of slightly deleterious mutations contributes to protein evolution at an extent negatively correlated with effective population size. While this supports the idea that functional evolution is not necessarily adaptive, comparative genomics is uncovering a role for positive Darwinian selection in 10,40% of all genes in different lineages, estimates that are likely to increase when the addition of more genomes gives increased power. Again, population size seems to matter also in this context, with a higher proportion of fixed amino acid changes representing advantageous mutations in large populations. Genes that are particularly prone to be driven by positive selection include those involved with reproduction, immune response, sensory perception and apoptosis. Genetic innovations are also frequently obtained by the gain or loss of complete gene sequences. Moreover, it is increasingly realized, from comparative genomics, that purifying selection conserves much more than just the protein-coding part of the genome, and this points at an important role for regulatory elements in trait evolution. Finally, genome sequencing using outbred or multiple individuals has provided a wealth of polymorphism data that gives information on population history, demography and marker evolution. [source]


Cross-species divergence of the major recognition pathways of ubiquitylated substrates for ubiquitin/26S proteasome-mediated proteolysis

FEBS JOURNAL, Issue 3 2010
Antony S. Fatimababy
The recognition of ubiquitylated substrates is an essential element of ubiquitin/26S proteasome-mediated proteolysis (UPP), which is mediated directly by the proteasome subunit RPN10 and/or RPN13, or indirectly by ubiquitin receptors containing ubiquitin-like and ubiquitin-associated domains. By pull-down and mutagenesis assays, we detected cross-species divergence of the major recognition pathways. RPN10 plays a major role in direct recognition in Arabidopsis and yeast based on the strong affinity for the long and K48-linked ubiquitin chains. In contrast, both the RPN10 and RPN13 homologs play major roles in humans. For indirect recognition, the RAD23 and DSK2 homologs (except for the human DSK2 homolog) are major receptors. The human RAD23 homolog is targeted to the 26S proteasome by the RPN10 and RPN13 homologs. In comparison, Arabidopsis uses UIM1 and UIM3 of RPN10 to bind DSK2 and RAD23, respectively. Yeast uses UIM in RPN10 and LRR in RPN1. Overall, multiple proteasome subunits are responsible for the direct and/or indirect recognition of ubiquitylated substrates in yeast and humans. In contrast, a single proteasome subunit, RPN10, is critical for both the direct and indirect recognition pathways in Arabidopsis. In agreement with these results, the accumulation of ubiquitylated substrates and severe pleiotropic phenotypes of vegetative and reproductive growth are associated with the loss of RPN10 function in an Arabidopsis T-DNA insertion mutant. This implies that the targeting and proteolysis of the critical regulators involved are affected. These results support a cross-species mechanistic and functional divergence of the major recognition pathways for ubiquitylated substrates of UPP. Structured digital abstract ,,A list of the large number of protein-protein interactions described in this article is available via the MINT article ID MINT-7307429 [source]


Studies on structural and functional divergence among seven WhiB proteins of Mycobacterium tuberculosis H37Rv

FEBS JOURNAL, Issue 1 2009
Md. Suhail Alam
The whiB -like genes (1-7) of Mycobacterium tuberculosis are involved in cell division, nutrient starvation, pathogenesis, antibiotic resistance and stress sensing. Although the biochemical properties of WhiB1, WhiB3 and WhiB4 are known, there is no information about the other proteins. Here, we elucidate in detail the biochemical and biophysical properties of WhiB2, WhiB5, WhiB6 and WhiB7 of M. tuberculosis and present a comprehensive comparative study on the molecular properties of all WhiB proteins. UV,Vis spectroscopy has suggested the presence of a redox-sensitive [2Fe,2S] cluster in each of the WhiB proteins, which remains stably bound to the proteins in the presence of 8 m urea. The [2Fe,2S] cluster of each protein was oxidation labile but the rate of cluster loss decreased under reducing environments. The [2Fe,2S] cluster of each WhiB protein responded differently to the oxidative effect of air and oxidized glutathione. In all cases, disassembly of the [2Fe,2S] cluster was coupled with the oxidation of cysteine-thiols and the formation of two intramolecular disulfide bonds. Both CD and fluorescence spectroscopy revealed that WhiB proteins are structurally divergent members of the same family. Similar to WhiB1, WhiB3 and WhiB4, apo WhiB5, WhiB6 and WhiB7 also reduced the disulfide of insulin, a model substrate. However, the reduction efficiency varied significantly. Surprisingly, WhiB2 did not reduce the insulin disulfide, even though its basic properties were similar to those of others. The structural and functional divergence among WhiB proteins indicated that each WhiB protein is a distinguished member of the same family and together they may represent a novel redox system for M. tuberculosis. [source]


Heterotachy and Functional Shift in Protein Evolution

IUBMB LIFE, Issue 4-5 2003
Hervé Philippe
Abstract Study of structure/function relationships constitutes an important field of research, especially for modification of protein function and drug design. However, the fact that rational design (i.e. the modification of amino acid sequences by means of directed mutagenesis, based on knowledge of the three-dimensional structure) appears to be much less efficient than irrational design (i.e. random mutagenesis followed by in vitro selection) clearly indicates that we understand little about the relationships between primary sequence, three-dimensional structure and function. The use of evolutionary approaches and concepts will bring insights to this difficult question. The increasing availability of multigene family sequences that has resulted from genome projects has inspired the creation of novel in silico evolutionary methods to predict details of protein function in duplicated (paralogous) proteins. The underlying principle of all such approaches is to compare the evolutionary properties of homologous sequence positions in paralogs. It has been proposed that the positions that show switches in substitution rate over time--i.e., 'heterotachous sites'--are good indicators of functional divergence. However, it appears that heterotachy is a much more general process, since most variable sites of homologous proteins with no evidence of functional shift are heterotachous. Similarly, it appears that switches in substitution rate are as frequent when paralogous sequences are compared as when orthologous sequences are compared. Heterotachy, instead of being indicative of functional shift, may more generally reflect a less specific process related to the many intra- and inter-molecular interactions compatible with a range of more or less equally viable protein conformations. These interactions will lead to different constraints on the nature of the primary sequences, consistently with theories suggesting the non-independence of substitutions in proteins. However, a specific type of amino acid variation might constitute a good indicator of functional divergence: substitutions occurring at positions that are generally slowly evolving. Such substitutions at constrained sites are indeed much more frequent soon after gene duplication. The identification and analysis of these sites by complementing structural information with evolutionary data may represent a promising direction to future studies dealing with the functional characterization of an ever increasing number of multi-gene families identified by complete genome analysis. IUBMB Life, 55: 257-265, 2003 [source]


A bacterial conjugation machinery recruited for pathogenesis

MOLECULAR MICROBIOLOGY, Issue 5 2003
Anja Seubert
Summary Type IV secretion systems (T4SS) are multicomponent transporters of Gram-negative bacteria adapted to functions as diverse as DNA transfer in bacterial conjugation or the delivery of effector proteins into eukaryotic target cells in pathogenesis. The generally modest sequence conservation between T4SS may reflect their evolutionary distance and/or functional divergence. Here, we show that the establishment of intraerythrocytic parasitism by Bartonella tribocorum requires a putative T4SS, which shares an unprecedented level of sequence identity with the Trw conjugation machinery of the broad-host-range antibiotic resistance plasmid R388 (up to 80% amino acid identity for individual T4SS components). The highly conserved T4SS loci are collinear except for the presence of numerous tandem gene duplications in B. tribocorum, which mostly encode variant forms of presumed surface-exposed pilus subunits. Conservation is not only structural, but also functional: R388 mutated in either trwD or trwH encoding essential T4SS components could be trans -complemented for conjugation by the homologues of the B. tribocorum system. Conservation also includes the transcription regulatory circuit: both T4SS loci encode a highly homologous and interchangeable KorA/KorB repressor system that negatively regulates the expression of all T4SS components. This striking example of adaptive evolution reveals the capacity of T4SS to assume dedicated functions in either DNA transfer or pathogenesis over rather short evolutionary distance and implies a novel role for the conjugation systems of widespread broad-host-range plasmids in the evolution of bacterial pathogens. [source]


POT1-independent single-strand telomeric DNA binding activities in Brassicaceae

THE PLANT JOURNAL, Issue 6 2009
Eugene V. Shakirov
Summary Telomeres define the ends of linear eukaryotic chromosomes and are required for genome maintenance and continued cell proliferation. The extreme ends of telomeres terminate in a single-strand protrusion, termed the G-overhang, which, in vertebrates and fission yeast, is bound by evolutionarily conserved members of the POT1 (protection of telomeres) protein family. Unlike most other model organisms, the flowering plant Arabidopsis thaliana encodes two divergent POT1-like proteins. Here we show that the single-strand telomeric DNA binding activity present in A. thaliana nuclear extracts is not dependent on POT1a or POT1b proteins. Furthermore, in contrast to POT1 proteins from yeast and vertebrates, recombinant POT1a and POT1b proteins from A. thaliana, and from two additional Brassicaceae species, Arabidopsis lyrata and Brassica oleracea (cauliflower), fail to bind single-strand telomeric DNA in vitro under the conditions tested. Finally, although we detected four single-strand telomeric DNA binding activities in nuclear extracts from B. oleracea, partial purification and DNA cross-linking analysis of these complexes identified proteins that are smaller than the predicted sizes of BoPOT1a or BoPOT1b. Taken together, these data suggest that POT1 proteins are not the major single-strand telomeric DNA binding activities in A. thaliana and its close relatives, underscoring the remarkable functional divergence of POT1 proteins from plants and other eukaryotes. [source]


Functionally redundant SHI family genes regulate Arabidopsis gynoecium development in a dose-dependent manner

THE PLANT JOURNAL, Issue 1 2006
Sandra Kuusk
Summary Gene duplication events, and the subsequent functional divergence of duplicates, are believed to be important evolutionary agents, driving morphological diversification. We have studied the structural and functional diversification of members of a plant-specific gene family in Arabidopsis thaliana by analysing mutant phenotypes, expression patterns and phylogeny. The SHI gene family comprises ten members that encode proteins with a RING finger-like zinc finger motif. We show that, despite being highly divergent in sequence, except in two conserved regions, many of the SHI -related genes are partially redundant in function and synergistically promote gynoecium, stamen and leaf development in Arabidopsis. Gynoecia of the loss-of-function sty1-1 mutant display subtle morphological defects, and, although mutations in the related STY2, SHI, SRS3, SRS4, SRS5, SRS7 and LRP1 genes have no apparent effect on gynoecium development, the sty1-1 mutant phenotype is gradually enhanced in double, triple, quadruple and quintuple mutant combinations, suggesting a remarkably extensive functional conservation within the family, which appears to be based on dosage dependency and protection against dominant negative mutations. In multiple mutant lines, all marginal tissues in the apical part of the gynoecium are dramatically reduced or missing, and our data indicate that SHI family members may promote formation of these tissues downstream of the transcriptional co-repressor LEUNIG (LUG). [source]


Analysis of functional divergence within two structurally related glycoside hydrolase families

BIOPOLYMERS, Issue 6 2009
Blake Mertz
Abstract Two glycoside hydrolase (GH) families were analyzed to detect the presence of functional divergence using the program DIVERGE. These two families, GH7 and GH16, each contain members related by amino acid sequence similarity, retaining hydrolytic mechanisms, and catalytic residue identity. GH7 and GH16 comprise GH Clan B, with a shared ,-jelly roll topology and mechanism. GH7 contains fungal cellobiohydrolases and endoglucanases and is divided into five main subfamilies, four of the former and one of the latter. Cluster comparisons between three of the cellobiohydrolase subfamilies and the endoglucanase subfamily identified specific amino acid residues that play a role in the functional divergence between the two enzyme types. GH16 contains subfamilies of bacterial agarases, xyloglucosyl transferases, 1,3-,- D -glucanases, lichenases, and other enzymes with various substrate specificities and product profiles. Four cluster comparisons between these four main subfamilies again have identified amino acid residues involved in functional divergence between the subfamilies. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 478,495, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source]


Structure of the thioredoxin-fold domain of human phosducin-like protein 2

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 2 2009
Xiaochu Lou
Human phosducin-like protein 2 (hPDCL2) has been identified as belonging to subgroup II of the phosducin (Pdc) family. The members of this family share an N-terminal helix domain and a C-terminal thioredoxin-fold (Trx-fold) domain. The X-ray crystal structure of the Trx-fold domain of hPDCL2 was solved at 2.70,Ĺ resolution and resembled the Trx-fold domain of rat phosducin. Comparative structural analysis revealed the structural basis of their putative functional divergence. [source]