@article{888, abstract = {BACKGROUND: Detection of changes in a protein's evolutionary rate may reveal cases of change in that protein's function. We developed and implemented a simple relative rates test in an attempt to assess the rate constancy of protein evolution and to detect cases of functional diversification between orthologous proteins. The test was performed on clusters of orthologous protein sequences from complete bacterial genomes (Chlamydia trachomatis, C. muridarum and Chlamydophila pneumoniae), complete archaeal genomes (Pyrococcus horikoshii, P. abyssi and P. furiosus) and partially sequenced mammalian genomes (human, mouse and rat). RESULTS: Amino-acid sequence evolution rates are significantly correlated on different branches of phylogenetic trees representing the great majority of analyzed orthologous protein sets from all three domains of life. However, approximately 1% of the proteins from each group of species deviates from this pattern and instead shows variation that is consistent with an acceleration of the rate of amino-acid substitution, which may be due to functional diversification. Most of the putative functionally diversified proteins from all three species groups are predicted to function at the periphery of the cells and mediate their interaction with the environment. CONCLUSIONS: Relative rates of protein evolution are remarkably constant for the three species groups analyzed here. Deviations from this rate constancy are probably due to changes in selective constraints associated with diversification between orthologs. Functional diversification between orthologs is thought to be a relatively rare event. However, the resolution afforded by the test designed specifically for genomic-scale datasets allowed us to identify numerous cases of possible functional diversification between orthologous proteins.}, author = {Jordan, Ingo and Kondrashov, Fyodor and Rogozin, Igor and Tatusov, Roman and Wolf, Yuri and Koonin, Eugene}, issn = {1465-6906}, journal = {Genome Biology}, number = {12}, publisher = {BioMed Central}, title = {{Constant relative rate of protein evolution and detection of functional diversification among bacterial, archaeal and eukaryotic proteins }}, doi = {10.1186/gb-2001-2-12-research0053}, volume = {2}, year = {2001}, } @article{1453, abstract = {In this Letter we exhibit a one-parameter family of new Taub-NUT instantons parameterized by a half-line. The endpoint of the half-line will be the reducible Yang-Mills instanton corresponding to the Eguchi-Hanson-Gibbons L2 harmonic 2-form, while at an inner point we recover the Pope-Yuille instanton constructed as a projection of the Levi-Civitá connection onto the positive su(2)+ ⊂ so(4) subalgebra. Our method imitates the Jackiw-Nohl-Rebbi construction originally designed for flat R4. That is we find a one-parameter family of harmonic functions on the Taub-NUT space with a point singularity, rescale the metric and project the obtained Levi-Civitá connection onto the other negative su(2)- ⊂ so(4) part. Our solutions will possess the full U(2) symmetry, and thus provide more solutions to the recently proposed U(2) symmetric ansatz of Kim and Yoon.}, author = {Etesi, Gábor and Hausel, Tamas}, issn = {0370-2693}, journal = {Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics}, number = {1-2}, pages = {189 -- 199}, publisher = {Elsevier}, title = {{Geometric construction of new Yang-Mills instantons over Taub-NUT space}}, doi = {10.1016/S0370-2693(01)00821-8}, volume = {514}, year = {2001}, } @article{1454, abstract = {We address the problem of finding Abelian instantons of finite energy on the Euclidean Schwarzschild manifold. This amounts to construct self-dual L2 harmonic 2-forms on the space. Gibbons found a non-topological L2 harmonic form in the Taub-NUT metric, leading to Abelian instantons with continuous energy. We imitate his construction in the case of the Euclidean Schwarzschild manifold and find a non-topological self-dual L2 harmonic 2-form on it. We show how this gives rise to Abelian instantons and identify them with SU(2)-instantons of Pontryagin number 2n2 found by Charap and Duff in 1977. Using results of Dodziuk and Hitchin we also calculate the full L2 harmonic space for the Euclidean Schwarzschild manifold.}, author = {Etesi, Gábor and Hausel, Tamas}, issn = {0393-0440}, journal = {Journal of Geometry and Physics}, number = {1-2}, pages = {126 -- 136}, publisher = {Elsevier}, title = {{Geometric interpretation of Schwarzschild instantons}}, doi = {10.1016/S0393-0440(00)00040-1}, volume = {37}, year = {2001}, } @article{855, abstract = {Motivation: The context of the start codon (typically, AUG) and the features of the 5′ Untranslated Regions (5′ UTRs) are important for understanding translation regulation in eukaryotic mRNAs and for accurate prediction of the coding region in genomic and cDNA sequences. The presence of AUG triplets in 5′ UTRs (upstream AUGs) might effect the initiation rate and, in the context of gene prediction, could reduce the accuracy of the identification of the authentic start. To reveal potential connections between the presence of upstream AUGs and other features of 5′ UTRs, such as their length and the start codon context, we undertook a systematic analysis of the available eukaryotic 5′ UTR sequences. Results: We show that a large fraction of 5′ UTRs in the available cDNA sequences, 15-53% depending on the organism, contain upstream ATGs. A negative correlation was observed between the information content of the translation start signal and the length of the 5′ UTR. Similarly, a negative correlation exists between the 'strength' of the start context and the number of upstream ATGs. Typically, cDNAs containing long 5′ UTRs with multiple upstream ATGs have a 'weak' start context, and in contrast, cDNAs containing short 5′ UTRs without ATGs have 'strong' starts. These counter-intuitive results may be interpreted in terms of upstream AUGs having an important role in the regulation of translation efficiency by ensuring low basal translation level via double negative control and creating the potential for additional regulatory mechanisms. One of such mechanisms, supported by experimental studies of some mRNAs, includes removal of the AUG-containing portion of the 5′ UTR by alternative splicing.}, author = {Rogozin, Igor and Kochetov, Alex and Kondrashov, Fyodor and Koonin, Eugene and Milanesi, Luciano}, issn = {1367-4803}, journal = {Bioinformatics}, number = {10}, pages = {890 -- 900}, publisher = {Oxford University Press}, title = {{Presence of ATG triplets in 5′ untranslated regions of eukaryotic cDNAs correlates with a 'weak'context of the start codon}}, doi = {10.1093/bioinformatics/17.10.890}, volume = {17}, year = {2001}, } @article{874, abstract = {Sex is thought to facilitate accumulation of initially rare beneficial mutations by allowing simultaneous allele replacements at many loci. However, this advantage of sex depends on a restrictive assumption that the fitness of a genotype is determined by fitness potential, a single intermediate variable to which all loci contribute additively, so that new alleles can accumulate in any order. Individual-based simulations of sexual and asexual populations reveal that under generic selection, sex often retards adaptive evolution. When new alleles are beneficial only if they accumulate in a prescribed order, a sexual population may evolve two or more times slower than an asexual population because only asexual reproduction allows some overlap of successive allele replacements. Many other fitness surfaces lead to an even greater disadvantage of sex. Thus, either sex exists in spite of its impact on the rate of adaptive allele replacements, or natural fitness surfaces have rather specific properties, at least at the scale of intrapopulation genetic variability.}, author = {Kondrashov, Fyodor and Kondrashov, Alexey}, issn = {0027-8424}, journal = {PNAS}, number = {21}, pages = {12089 -- 12092}, publisher = {National Academy of Sciences}, title = {{Multidimensional epistasis and the disadvantage of sex}}, doi = {10.1073/pnas.211214298}, volume = {98}, year = {2001}, }