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Recombinatoric exploration of novel folded structures: a heteropolymer-based model of protein evolutionary landscapes.

The role of recombination in evolution is compared with that of point mutations (substitutions) in the context of a simple, polymer physics-based model mapping between sequence (genotype) and conformational (phenotype) spaces. Crossovers and point mutations of lattice chains with a hydrophobic polar code are investigated. Sequences encoding for a single ground-state conformation are considered viable and used as model proteins. Point mutations lead to diffusive walks on the evolutionary landscape, whereas crossovers can "tunnel" through barriers of diminished fitness. The degree to which crossovers allow for more efficient sequence and structural exploration depends on the relative rates of point mutations versus that of crossovers and the dispersion in fitness that characterizes the ruggedness of the evolutionary landscape. The probability that a crossover between a pair of viable sequences results in viable sequences is an order of magnitude higher than random, implying that a sequence's overall propensity to encode uniquely is embodied partially in local signals. Consistent with this observation, certain hydrophobicity patterns are significantly more favored than others among fragments (i.e., subsequences) of sequences that encode uniquely, and examples reminiscent of autonomous folding units in real proteins are found. The number of structures explored by both crossovers and point mutations is always substantially larger than that via point mutations alone, but the corresponding numbers of sequences explored can be comparable when the evolutionary landscape is rugged. Efficient structural exploration requires intermediate nonextreme ratios between point-mutation and crossover rates.

Biophysical Phenomena↗

Molecular evolution of aromatic polyketides and comparative sequence analysis of polyketide ketosynthase and 16S ribosomal DNA genes from various streptomyces species.

A 613-bp fragment of an essential ketosynthase gene from the biosynthetic pathway of aromatic polyketide antibiotics was sequenced from 99 actinomycetes isolated from soil. Phylogenetic analysis showed that the isolates clustered into clades that correspond to the various classes of aromatic polyketides. Additionally, sequencing of a 120-bp fragment from the gamma-variable region of 16S ribosomal DNA (rDNA) and subsequent comparative sequence analysis revealed incongruity between the ketosynthase and 16S rDNA phylogenetic trees, which strongly suggests that there has been horizontal transfer of aromatic polyketide biosynthesis genes. The results show that the ketosynthase tree could be used for DNA fingerprinting of secondary metabolites and for screening interesting aromatic polyketide biosynthesis genes. Furthermore, the movement of the ketosynthase genes suggests that traditional marker molecules like 16S rDNA give misleading information about the biosynthesis potential of aromatic polyketides, and thus only molecules that are directly involved in the biosynthesis of secondary metabolites can be used to gain information about the biodiversity of antibiotic production in different actinomycetes.

Anti-Bacterial Agents↗

Plasticity and patterns of evolution in mammalian salivary glands: comparative immunohistochemistry of lysozyme in bats.

Salivary gland plasticity was a significant adaptive feature in the mammalian radiation. This plasticity is reflected in remarkable and well-documented interspecific phenotypic variation in gland ultrastructure and in the chemical components of saliva. However, comparative data are still too sparse for determination of evolutionary trends that combine phenotypic patterns with evolutionary history and the actual secretory products. Although our theoretical approach assumes that natural selection has taken advantage of salivary gland plasticity in gene regulation, gland development, and secretory cell organelles and processes, it still is difficult to delineate the biological roles of secretory products in the context of ecological adaptation. In the present investigation we used immunohistochemical techniques and a polyclonal antiserum against lysozyme to compare the parotid and principal submandibular glands in a set of 12 species of microchiropteran bats. With this data set we used comparative methods and phylogenetic trees to develop the foundations for testable hypotheses about the molecular genetics and adaptive significance of lysozyme production in bats. By comparing immunohistochemical results with ultrastructure, lysozyme-like immunoreactivity was associated with serous secretory granules in parotid gland acinar calls, parotid gland intercalated duct cells, and submandibular gland demilune cells. Lysozyme production in submandibular gland demilune cells marks a point of evolutionary divergence between three families of insectivorous bats and four families composed of species with diverse diets (ranging from carnivory to nectarivory). In terms of diet, lysozyme-like immunoreactivity corresponded most strongly with feeding on hard-bodied insects, leading to the hypothesis that lysozyme serves as an important chitinase in bat saliva.

Adaptation, Physiological↗

[Fibrous fixed subaortic stenosis].

Fifty eight patients with isolated with discrete subaortic stenosis or in association with just another heart defect, were studied between 1961 and 1980. The age range was between 2 and 42 years. The evaluation of each case was done according to clinical manifestations, systolic overloading of the left ventricle and the amount of the systolic gradient. There is a poor correlation between the clinical, electrocardiographic and hemodynamic parameters according to the student t test in the preoperative evaluation. Forty-one patients were operated, two of them died in the early post-operative period. There was a good clinical evolution with significant values comparing pre and post-operative symptoms. The decrease in the systolic gradient in 26 cases after surgery was significative (p less than or equal to 0.005). Based on the natural history of this malformation and on the results obtained with the surgical treatment, we may conclude that there is surgical indication once the diagnosis is made, because this malformation has a completely different evolution compared with other forms of congenital aortic stenosis.

Adolescent↗

Within- and between-species DNA sequence variation and the 'footprint' of natural selection.

Extensive DNA data emerging from genome-sequencing projects have revitalized interest in the mechanisms of molecular evolution. Although the contribution of natural selection at the molecular level has been debated for over 30 years, the relevant data and appropriate statistical methods to address this issue have only begun to emerge. This paper will first present the predominant models of neutral, nearly neutral, and adaptive molecular evolution. Then, a method to identify the role of natural selection in molecular evolution by comparing within- and between-species DNA sequence variation will be presented. Computer simulations show that such methods are powerful for detecting even very weak selection. Examination of DNA variation data within and between Drosophila species suggests that 'silent' sites evolve under a balance between weak selection and genetic drift. Simulated data also show that sequence comparisons are a powerful method to detect adaptive protein evolution, even when selection is weak or affects a small fraction of nucleotide sites. In the Drosophila data examined, positive selection appears to be a predominant force in protein evolution.

DNA↗

[Quantitative analysis of the teleost brain: evolution and adaptation. 1. A comparative interspecies study].

The intraspecific brain-body weight allometric coefficient, although high in Teleosts (0.49), is different enough from the interspecific one (0.65, almost 2/3) to use only adult specimens for quantitative studies. The low encephalization level of species of great size makes the use of a quadratic curve preferable, although not well adapted to small species. The mean variability of encephalization indices within the species is 8%. Differences of encephalization are noted either between sexes (Misgurnus fossilis) or between ecological milieus (Ictalurus melas). The variability increases progressively from species to genus, family and order; the allometric coefficient grows also, following the general trend for a larger encephalization when the body size is greater. The correlation between the encephalization index and the position within the classification is low; the great number of exceptions makes it necessary to look for other biological and ecological factors, such as the body form, the type of locomotion, the general activity level, the food habits, the way fishes avoid predation and social organization. The index value is due either to the modification of the body size (overweight due to the elongated form of the body, the ballast of poor diets: limivores, coral or sponge eaters, the passive protection against predators of thick scales, spines, etc), or to that of the brain size. In that case, a better encephalization is to be noted in species with a fusiform body, swimming with lateral beats of the caudal peduncle, in active species from mid-waters or pelagic, in predators actively hunting their prey, in species using active ways of protection against predation, in diurnal fishes and in those which have a social way of life needing a good knowledge either of their milieu (territorial behaviour) or of their congeners (social behaviour).

Animals↗

[The trends in cancer mortality, especially lung cancer, in Spain compared with other developed countries].

In this paper we study the general mortality trends by cancer in Spain (1951-1987), and also by sex and age groups. We focus on lung cancer, establishing comparisons with USA, England and Wales. We appreciate on the general mortality trend that only young age groups show a higher decrease, while in other countries this decrease was also in old age groups. We observed a lower mortality trend in Spain by lung cancer than in the other countries, however increasing the rates in both sexes and more in males. That evolution could be related with the evolution of cancer risk factors and especially lung cancer. On concluded that the general mortality trend in Spain is the same than other developed countries but with some delay in the evolution, when comparing lung cancer. Spain is now in an increasing phase and USA, England and Wales have stabilized their rates and begin to decrease their trends.

Adult↗

Predicting protein-protein interaction by searching evolutionary tree automorphism space.

MOTIVATION: Uncovering the protein-protein interaction network is a fundamental step in the quest to understand the molecular machinery of a cell. This motivates the search for efficient computational methods for predicting such interactions. Among the available predictors are those that are based on the co-evolution hypothesis "evolutionary trees of protein families (that are known to interact) are expected to have similar topologies". Many of these methods are limited by the fact that they can handle only a small number of protein sequences. Also, details on evolutionary tree topology are missing as they use similarity matrices in lieu of the trees. RESULTS: We introduce MORPH, a new algorithm for predicting protein interaction partners between members of two protein families that are known to interact. Our approach can also be seen as a new method for searching the best superposition of the corresponding evolutionary trees based on tree automorphism group. We discuss relevant facts related to the predictability of protein-protein interaction based on their co-evolution. When compared with related computational approaches, our method reduces the search space by approximately 3 x 10(5)-fold and at the same time increases the accuracy of predicting correct binding partners.

Algorithms↗

Divergent origins and concerted expansion of two segmental duplications on chromosome 16.

An unexpected finding of the human genome was the large fraction of the genome organized as blocks of interspersed duplicated sequence. We provide a comparative and phylogenetic analysis of a highly duplicated region of 16p12.2, which is composed of at least four different segmental duplications spanning in excess of 160 kb. We contrast the dispersal of two different segmental duplications (LCR16a and LCR16u). LCR16a, a 20 kb low-copy repeat sequence A from chromosome 16, was shown previously to contain a rapidly evolving novel hominoid gene family (morpheus) that had expanded within the last 10 million years of great ape/human evolution. We compare the dispersal of this genomic segment with a second adjacent duplication called LCR16u. The duplication contains a second putative gene family (KIAA0220/SMG1) that is represented approximately eight times within the human genome. A high degree of sequence identity (approximately 98%) was observed among the various copies of LCR16u. Comparative analyses with Old World monkey species show that LCR16a and LCR16u originated from two distinct ancestral loci. Within the human genome, at least 70% of the LCR16u copies were duplicated in concert with the LCR16a duplication. In contrast, only 30% of the chimpanzee loci show an association between LCR16a and LCR16u duplications. The data suggest that the two copies of genomic sequence were brought together during the chimpanzee/human divergence and were subsequently duplicated as a larger cassette specifically within the human lineage. The evolutionary history of these two chromosome-specific duplications supports a model of rapid expansion and evolutionary turnover among the genomes of man and the great apes.

Animals↗

[Survivorship of breast implants used in breast reconstruction. 949 implants].

The authors present from a series of 949 implants their method to calculate the life span of a mammary implant in the framework of breast reconstruction after cancer. In this statistical study, they have calculated the median life span of breast implants (loss of half of staff) by distinguishing it according to each type of implant (content, brand, indication...). The global median life span of a breast implant is 127 months. The median life span of a silicone gel-filled implant is superior than a saline implant because the frequency of deflation of saline implants is more important than the first one, despite that the real rupture percentage of silicone gel-filled implants is under-evaluated by the number of asymptomatic rupture. For saline implants, the median life span is clearly decreased by the initial under-inflation (108 months against 127 months) doubling the secondary deflation risk. In this series, the authors have been able to compare the evolution of implants according to their initial indication (reconstruction or aesthetic) and sometimes at a same patient, they have not observed significant difference of the median life span over a period of five years for an implant used in breast reconstruction after cancer or for an implant used in symmetricalization. In this series, the life span of saline implants is significant different in function of the brand of the implant demonstrating the comparative study usefulness by brands.

Adult↗

[Pregnancy in adolescents. Complications, birth weight, somatometry of the newborn and Apgar score, comparison with the general population].

The objective of this study was to compare pregnancy evolution, newborn's weight, its somatometry and Apgar's qualification of teenagers and the general population in a community where the socio-economic factor is similar among those two groups. Three hundred and two pregnancies in teenagers were analyzed, 69 of 12-15 years and 233 of 16-17 years at the time of pregnancy, against a control group of 304 pregnant patients of 18-39 years. It was a prospective, comparative, longitudinal study. Average age at the first delivery of the 606 patients was 18.1 years. There were no significant difference among the groups as to occupation. There was not significant difference among the three groups as to pre-natal control, weeks of gestation incidence of threatening abortion, toxemia, bleeding of the second half of pregnancy, premature rupture of membranes, proportion of deliveries and cesarean sections, as well as forceps application and newborns' sex. The most common indications of cesarean section in teenagers were CPD and acute fetal suffering, in the control group were CPD and pelvic presentation. There was significant difference comparing the weight, Apgar qualification at one minute and at three minutes in the 16-17 years group, and older of 18 years being greatest in the last group. There was significant difference in size, cephalic perimeter, thoracic perimeter and PC/pa ratio among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparison of 1-year follow-up evaluations of patients with indication for pallidotomy who did not undergo surgery versus patients with Parkinson's disease who did undergo pallidotomy: a case control study.

UNLABELLED: Many reports published during the past 5 years have shown evidence of the beneficial effect of posteroventral pallidotomy (PVP) in large groups of patients for up to 3 years, but none of them have compared patients who underwent surgery with a control group. OBJECTIVE: To compare the evolution of Parkinson's disease symptoms at 1-year follow-up between patients who underwent surgery and those who did not. MATERIAL AND METHODS: Ten patients with idiopathic Parkinson's disease refractory to treatment who were included in the Core Assessment for Intracerebral Transplantation program for PVP did not undergo surgery because financial support was lacking. These patients were followed up for 1 year as if they had been operated on and were finally compared with 10 patients having similar characteristics in whom PVP had been performed during the same period of time. RESULTS: There were no significant differences at basal evaluation in the motor section scores of the Unified Parkinson's Disease Rating Scale between those patients who underwent surgery and those who did not, but a significant reduction in Unified Parkinson's Disease Rating Scale motor score in the group who underwent surgery at 1-year evaluation was found (P < 0.006). Dyskinesias, which was nonsignificantly different at basal evaluation, showed, at the 1-year follow-up, a significant reduction in the group who underwent surgery (P < 0.04). Scores from the subsets of the Unified Parkinson's Disease Rating Scale addressing rigidity, tremor, and bradykinesia also proved significantly different at the 1-year follow-up. The slope of the line generated by the two evaluations for each group showed a negative value in the group who underwent surgery (value of -0.21) and a positive value in the group who did not (value of 0.148). CONCLUSION: At the 1-year follow-up, microelectrode-guided PVP produced significant changes in patient motor status and disease progression versus a comparable group of patients who did not undergo surgery during the same period of time.

Aged↗

A genetic linkage map of the mouse: current applications and future prospects.

Technological advances have made possible the development of high-resolution genetic linkage maps for the mouse. These maps in turn offer exciting prospects for understanding mammalian genome evolution through comparative mapping, for developing mouse models of human disease, and for identifying the function of all genes in the organism.

Animals↗

Two patterns of genome organization in mammals: the chromosomal distribution of duplicate genes in human and mouse.

Gene duplication occurs repeatedly in the evolution of genomes, and the rearrangement of genomic segments has also occurred repeatedly over the evolution of eukaryotes. We studied the interaction of these two factors in mammalian evolution by comparing the chromosomal distribution of multigene families in human and mouse. In both species, gene families tended to be confined to a single chromosome to a greater extent than expected by chance. The average number of families shared between chromosomes was nearly 60% higher in mouse than in human, and human chromosomes rarely shared large numbers of gene families with more than one or two other chromosomes, whereas mouse chromosomes frequently did so. A higher proportion of duplicate gene pairs on the same chromosome originated from recent duplications in human than in mouse, whereas a higher proportion of duplicate gene pairs on separate chromosomes arose from ancient duplications in human than in mouse. These observations are most easily explained by the hypotheses that (1) most gene duplications arise in tandem and are subsequently separated by segmental rearrangement events, and (2) that the process of segmental rearrangement has occurred at a higher rate in the lineage of mouse than in that of human.

Animals↗

Probing fungal mitochondrial evolution with tRNA.

Sequence data are now available for almost the entire complement of mitochondrial rRNAs from five fungi: Schizosaccharomyces pombe, Saccharomyces cerevisiae, Toropulis glabrata, Aspergillus nidulans and Neurospora crassa. Analysis of these data show that the five mitochondria can be related to a common ancestor. The unusually high similarity between some S. pombe mt tRNAs may be due to a process similar to gene conversion. Using the number of differences between tRNA pairs as a measure of the evolutionary rate the yeast-S. pombe branch has paradoxically a high nuclear rate and a low mt rate of evolution as compared with other branches in the phylogenetic tree. Finally the position of mt tRNA genes in S. pombe is abnormally distinct from gene orders in other mitochondria. All of the above factors must be taken into account when describing the relationship between these mitochondria.

Base Sequence↗

The molecular evolution of signal peptides.

Signal peptides direct mature peptides to their appropriate cellular location, after which they are cleaved off. Very many random alternatives can serve the same function. Of all coding sequences, therefore, signal peptides might come closest to being neutrally evolving. Here we consider this issue by examining the molecular evolution of 76 mouse-rat orthologues, each with defined signal peptides. Although they do evolve rapidly, they evolve about half as fast as neutral sequences. This indicates that a substantial proportion of mutations must be under stabilizing selection. A few putative signal sequences lack a hydrophobic core and these tend to be more slowly evolving than others, indicating even stronger stabilizing selection. However, closer scrutiny suggests that some of these represent mis-annotations in GenBank. It is also likely that some of the substitutions are not neutral. We find, for example, that the rate of protein evolution correlates with that of the mature peptide. This may be a result of compensatory evolution. We also find that signal peptides of immune genes tend to be faster evolving than the average, which suggests an association with antagonistic co-evolution. Previous reports also indicated that the signal peptide of the imprinted gene, Igf2r, is also unusually fast evolving. This, it was hypothesized, might also be indicative of antagonistic co-evolution. Comparison of Igf2r's signal peptide evolution shows that, although it is not an outlier, its rate of evolution is comparable to that of many of the faster evolving immune system signal sequences and 5/6 of the amino acid changes do not conserve hydrophobicity. This is at least suggestive that there is something unusual about Igf2r's signal sequence.

Amino Acid Substitution↗

[Hormone dependence in functional thyroid cancers, survival after total thyroidectomy combined with radioactive iodine and thyroid extract therapy].

The authors reviewed current criteria on hormone-dependence in functional thyroid cancers, presenting data of compared disease evolution based on the casuistics of thyroid carcinomas from the files of the Fundación Jiménez Díaz, with 5 and 10 year follow-up studies in some of the cases. They found a higher number of survivors among the patients with papilliferous carcinoma in both 5 and 10 year follow-up groups whom, aside total surgical removal of the gland and the administration of thyroid extracts, those who had thyroid residues left were given 100 mc of 131I. Among the patients with follicular adenocarcinoma, under the same comparative conditions, differences were not very clear in the 5 year follow-up group, while the 10 year follow-up group showed marked differences. The authors conclude that an adequate combination of the three therapeutic procedures may allow a higher survival rate.

Adenocarcinoma↗

The spread of sequence variants in Rattus satellite DNAs.

The genus Rattus has two related families of satellite DNA: Satellite I consists of tandem arrays of a 370 base pair repeat unit which is a dimer of two 185 base pair portions (a, b) which are about 60% homologous. Satellite I' consists of tandem arrays of a 185 base pair repeat unit (a') which is about 85% homologous to a and 60% homologous to b. R. norvegicus contains only satellite I but R. rattus contains both satellites I and I'. We examined certain aspects of satellite DNA evolution by comparing the spacing at which variant repeat units of each satellite have spread among non-variant repeat units in these two species. With but one exception, in R. rattus, 15 different variant repeat units have spread among non-variant repeat units of satellite I, with a spacing equal to the length of the (a,b) dimer. Similarly, fourteen different variant repeat units of the monomeric satellite I' have mixed among non-variant repeat units with a spacing equal to the length of the (a') monomer. These results suggest that a mechanism involving homologous interaction among satellite sequences could account for the spread of variant family members. We also found that a sequence variant present in certain portions of the dimeric repeat unit of satellite I is more efficiently amplified (or less efficiently corrected) than variants occurring in other regions. This was not true for the monomeric repeat unit of satellite I'.

Animals↗