Molecular polytomies

This paper focuses on polytomies, especially molecular polytomies. The distinction between molecular and species polytomies is important, but is often not made. Likelihood ratio tests are an easier method for detecting molecular polytomies than other methods cited herein. Simulation shows that parsimony will generally falsely resolve molecular polytomies, which is worrisome because a simple mathematical model described herein predicts that molecular polytomies will occur often when the mean branch length is small. A test of the model using several real molecular data sets indicates that molecular polytomies may actually occur more often than predicted by the model. This suggests that at least some published molecular parsimony trees contain clades that are false resolutions of polytomies. Finally, a possible method for detecting species polytomies from molecular data is described.     

Body mass‐corrected molecular rate for bird mitochondrial DNA

Mitochondrial DNA remains one of the most widely used molecular markers to reconstruct the phylogeny and phylogeography of closely related birds. It has been proposed that bird mitochondrial genomes evolve at a constant rate of ~0.01 substitution per site per million years, that is that they evolve according to a strict molecular clock. This molecular clock is often used in studies of bird mitochondrial phylogeny and molecular dating. However, rates of mitochondrial genome evolution vary among bird species and correlate with life history traits such as body mass and generation time. These correlations could cause systematic biases in molecular dating studies that assume a strict molecular clock. In this study, we overcome this issue by estimating corrected molecular rates for birds. Using complete or nearly complete mitochondrial genomes of 475 species, we show that there are strong relationships between body mass and substitution rates across birds. We use this information to build models that use bird species’ body mass to estimate their substitution rates across a wide range of common mitochondrial markers. We demonstrate the use of these corrected molecular rates on two recently published data sets. In one case, we obtained molecular dates that are twice as old as the estimates obtained using the strict molecular clock. We hope that this method to estimate molecular rates will increase the accuracy of future molecular dating studies in birds.     

Ruthless reductionism and social cognition

Social cognition appears to present phenomena that "ruthlessly reductive" molecular and cellular neuroscience cannot fruitfully investigate or explain. This is because the causes of such phenomena are distal and external not only to the molecular machinery of individual neurons, but to individual brains. However, the "reductionist's epiphany" insists that to the extent that we understand the specific molecular mechanisms that underlie phenomena upon which most or all social cognition depends, we can be sure that molecular mechanisms for the broader phenomena can be found using standard experimental methods from molecular and cellular cognition. Furthermore, social recognition memory consolidation is required for virtually all types of social cognition, and its specific molecular mechanisms have now been uncovered experimentally. These same molecular mechanisms obtain across a wide variety of divergent species (from invertebrates to vertebrates). Thus we can expect to find the molecular mechanisms of the broader social cognitive functions that must "plug into" these specific molecular mechanisms, despite these functions' typically distal, external initial causes. This conclusion rests on explicit scientific facts, not just on some vague philosophical commitment to physicalism about mind.     

Biosynthesis of triacylglycerol molecular species in an oleaginous fungus,Mortierella ramanniana var. angulispora

The incorporation of radiolabeled lipid precursors into triacylglycerol (TG) molecular species in Mortierella ramanniana var. angulispora, an oleaginous fungus, was studied to determine the biosynthetic pathways for TG molecular species. Radiolabeled TG molecular species were separated and quantified by reverse-phase high performance liquid chromatography with a radioisotope detector. The major TG molecular species labeled by [1-(14)C]oleic acid at 30 degrees C were OOP, OOO, and OPP (TG molecular species designations represent three constituent acyl groups. G, gamma-linolenic acid; L, linoleic acid; O, oleic acid; S, stearic acid; P, palmitic acid), which were abundant TG molecular species in this fungus. The incorporation of [1-(14)C]oleic acid at 15 degrees C into these molecular species was the same, while that into most other species was decreased, suggesting that biosynthesis of major molecular species such as OOP, OOO, and OPP differs from that of other TG molecular species. [1-(14)C]Linoleic acid incorporation indicated that the major labeled molecular species were LOP and LOO, which may be due to acylation of oleoyl, palmitoyl-glycerol, or dioleoyl-glycerol by exogenous linoleic acid. This is basically the same mechanism as for OOP and OOO biosynthesis from exogenous oleic acid. [(14)C(U)]Glycerol incorporation suggested that TG molecular species containing palmitic acid such as OPP were more readily synthesized through the de novo pathway. Further experiments involving inhibitors such as sodium azide and cerulenin suggested that OOO biosynthesis included a mechanism differing from that in the cases of OOP and OPP. Trifluoperazine, which inhibits the conversion from phosphatidic acid to TG, decreased [1-(14)C]oleic acid incorporation into all molecular species, suggesting that the incorporation into all molecular species included the de novo TG biosynthetic pathway via phosphatidic acid. These results revealed that the biosynthetic pathways for TG molecular species can be classified into several groups, which exhibit different sensitivities to low temperature and inhibitors of lipid metabolism. This implies that the composition of TG molecular species is regulated through different biosynthetic pathways responsible for specific TG molecular species, providing a new insight into the biosynthesis of TG molecular species.     

Mapping Molecular Association Networks of Nervous System Diseases via Large-Scale Analysis of Published Research

Network medicine has been applied successfully to elicit the structure of large-scale molecular interaction networks. Its main proponents have claimed that this approach to integrative medical investigation should make it possible to identify functional modules of interacting molecular biological units as well as interactions themselves. This paper takes a significant step in this direction. Based on a large-scale analysis of the nervous system molecular medicine literature, this study analyzes and visualizes the complex structure of associations between diseases on the one hand and all types of molecular substances on the other. From this analysis it then identifies functional co-association groups consisting of several types of molecular substances, each consisting of substances that exhibit a pattern of frequent co-association with similar diseases. These groups in turn exhibit interlinking in a complex pattern, suggesting that such complex interactions between functional molecular modules may play a role in disease etiology. We find that the patterns exhibited by the networks of disease – molecular substance associations studied here correspond well to a number of recently published research results, and that the groups of molecular substances identified by statistical analysis of these networks do appear to be interesting groups of molecular substances that are interconnected in identifiable and interpretable ways. Our results not only demonstrate that networks are a convenient framework to analyze and visualize large-scale, complex relationships among molecular networks and diseases, but may also provide a conceptual basis for bridging gaps in experimental and theoretical knowledge.     

Homology in classical and molecular biology

Hypotheses of homology are the basis of comparative morphology and comparative molecular biology. The kinds of homologous and nonhomologous relations in classical and molecular biology are explored through the three tests that may be applied to a hypothesis of homology: congruence, conjunction, and similarity. The same three tests apply in molecular comparisons and in morphology, and in each field they differentiate eight kinds of relation. These various relations are discussed and compared. The unit or standard of comparison differs in morphology and in molecular biology; in morphology it is the adult or life cycle, but with molecules it is the haploid genome. In morphology the congruence test is decisive in separating homology and nonhomology, whereas with molecular sequence data similarity is the decisive test. Consequences of this difference are that the boundary between homology and nonhomology is not the same in molecular biology as in morphology, that homology and synapomorphy can be equated in morphology but not in all molecular comparisons, and that there is no detected molecular equivalent of convergence. Since molecular homology may reflect either species phylogeny or gene phylogeny, there are more kinds of homologous relation between molecular sequences than in morphology. The terms paraxenology and plerology are proposed for two of these kinds--respectively, the consequence of multiple xenology and of gene conversion.     

Atrial natriuretic factor: atrial conversion of high to low molecular weight forms

The atrial natriuretic factor elutes by gel filtration in high and low molecular weight fractions. Extraction and elution of rat atria in 1.0 M acetic acid yielded a predominance of the high molecular weight form(s); whereas when these procedures were carried out in 0.1 M acetic acid, there was a predominance of the low molecular weight forms. When partially purified high molecular weight natriuretic activity was eluted in 0.1 M acetic acid, the high molecular weight form(s) remained intact. When partially purified high molecular weight natriuretic activity was mixed with crude atrial extract in 0.1 M acetic acid, there was an apparent conversion to the low molecular weight forms. Extraction of rat atria in boiling 0.1 M acetic acid blocked this conversion. It is concluded that rat atria contain a heat labile factor that converts high molecular weight natriuretic activity to the low molecular weight forms.     

Understanding Neutral Genomic Molecular Clocks

The molecular clock hypothesis is a central concept in molecular evolution and has inspired much research into why evolutionary rates vary between and within genomes. In the age of modern comparative genomics, understanding the neutral genomic molecular clock occupies a critical place. It has been demonstrated that molecular clocks run differently between closely related species, and generation time is an important determinant of lineage specific molecular clocks. Moreover, it has been repeatedly shown that regional molecular clocks vary even within a genome, which should be taken into account when measuring evolutionary constraint of specific genomic regions. With the availability of a large amount of genomic sequence data, new insights into the patterns and causes of variation in molecular clocks are emerging. In particular, factors such as nucleotide composition, molecular origins of mutations, weak selection and recombination rates are important determinants of neutral genomic molecular clocks.     

Congruence of Morphological and Molecular Phylogenies

When phylogenetic trees constructed from morphological and molecular evidence disagree (i.e. are incongruent) it has been suggested that the differences are spurious or that the molecular results should be preferred a priori. Comparing trees can increase confidence (congruence), or demonstrate that at least one tree is incorrect (incongruence). Statistical analyses of 181 molecular and 49 morphological trees shows that incongruence is greater between than within the morphological and molecular partitions, and this difference is significant for the molecular partition. Because the level of incongruence between a pair of trees gives a minimum bound on how much error is present in the two trees, our results indicate that the level of error may be underestimated by congruence within partitions. Thus comparisons between morphological and molecular trees are particularly useful for detecting this incongruence (spurious or otherwise). Molecular trees have higher average congruence than morphological trees, but the difference is not significant, and both within- and between-partition incongruence is much lower than expected by chance alone. Our results suggest that both molecular and morphological trees are, in general, useful approximations of a common underlying phylogeny and thus, when molecules and morphology clash, molecular phylogenies should not be considered more reliable a priori.     

Continuous Changes in Triacylglycerol Molecular Species Composition by Fatty Acids in Porcine Adipocytes

It has been demonstrated that the composition of molecular species of adipose tissue triacylglycerols (TGs) from farm animals are not equally synthesized and that some molecular species are preferentially synthesized. The objective of the present study was to determine whether exogenous fatty acids (FAs) would affect the TG composition. To this end, the composition of TG molecular species stored in porcine adipocytes differentiated with several long-chain FAs was analyzed by gas chromatography. The addition of each FA for 6 d increased TG molecular species having two or three added FAs. However, the molecular species compositions at 15 d after the addition of each FA resembled those of cells with no added FAs. Moreover, some common molecular species in all experimental cells increased, as well as cells with no added FAs. It was concluded that the addition of FAs increases the contents of specific molecular species, but does not affect the synthetic processes of individual TG molecular species.     

Molecular sled sequences are common in mammalian proteins

Recent work revealed a new class of molecular machines called molecular sleds, which are small basic molecules that bind and slide along DNA with the ability to carry cargo along DNA. Here, we performed biochemical and single-molecule flow stretching assays to investigate the basis of sliding activity in molecular sleds. In particular, we identified the functional core of pVIc, the first molecular sled characterized; peptide functional groups that control sliding activity; and propose a model for the sliding activity of molecular sleds. We also observed widespread DNA binding and sliding activity among basic polypeptide sequences that implicate mammalian nuclear localization sequences and many cell penetrating peptides as molecular sleds. These basic protein motifs exhibit weak but physiologically relevant sequence-nonspecific DNA affinity. Our findings indicate that many mammalian proteins contain molecular sled sequences and suggest the possibility that substantial undiscovered sliding activity exists among nuclear mammalian proteins.     

堆肥处理对污泥腐殖物质形态及其重金属分配的影响

采用透析、凝胶色谱 (SephadexG 75 )研究了污泥堆肥前后腐殖质分子大小的变化及重金属Cu和Zn在各级组分中的分配。透析结果表明 ,污泥经过堆腐以后 ,腐殖质中小分子物质 (<10 0 0Da)组分的含量下降 6 4 % ,而相对高分子组分 (>2 5 0 0 0Da)却增加了 6 8%。凝胶色谱进一步证实 ,污泥经过 4 9d堆腐后 ,腐殖质中大于 2 0 0 0KDa的大分子组分是堆肥起始时的2 3倍。而小分子组分明显减少 ,表现在小分子组分的凝胶洗脱体积明显减少。堆肥腐熟以后 ,腐殖质吸附的Cu、Zn元素含量增加 ,其中Cu主要被吸附在大分子物质上 ,而Zn主要与小分子物质结合     

Real-time and quantitative PCR: applications to mechanism-based toxicology.

There is increasing awareness that quantitative analysis of changes in molecular targets plays a key role in addressing scientific questions in molecular toxicology, molecular epidemiology, and human risk assessment. One of the emerging technologies that is being used to analyze these molecular targets is real-time and quantitative (RTAQ) polymerase chain reaction (PCR). The aim of this review is to provide the reader with an overview of this technology and to highlight specific applications of this technology to some key areas of molecular toxicology.     

Continuous changes in triacylglycerol molecular species composition by fatty acids in porcine adipocytes

It has been demonstrated that the composition of molecular species of adipose tissue triacylglycerols (TGs) from farm animals are not equally synthesized and that some molecular species are preferentially synthesized. The objective of the present study was to determine whether exogenous fatty acids (FAs) would affect the TG composition. To this end, the composition of TG molecular species stored in porcine adipocytes differentiated with several long-chain FAs was analyzed by gas chromatography. The addition of each FA for 6 d increased TG molecular species having two or three added FAs. However, the molecular species compositions at 15 d after the addition of each FA resembled those of cells with no added FAs. Moreover, some common molecular species in all experimental cells increased, as well as cells with no added FAs. It was concluded that the addition of FAs increases the contents of specific molecular species, but does not affect the synthetic processes of individual TG molecular species.     

Why do species vary in their rate of molecular evolution?

Despite hopes that the processes of molecular evolution would be simple, clock-like and essentially universal, variation in the rate of molecular evolution is manifest at all levels of biological organization. Furthermore, it has become clear that rate variation has a systematic component: rate of molecular evolution can vary consistently with species body size, population dynamics, lifestyle and location. This suggests that the rate of molecular evolution should be considered part of life-history variation between species, which must be taken into account when interpreting DNA sequence differences between lineages. Uncovering the causes and correlates of rate variation may allow the development of new biologically motivated models of molecular evolution that may improve bioinformatic and phylogenetic analyses.     

Cells as semantic systems

Background

We consider cells as biological systems that process information by means of molecular codes. Many studies analyze cellular information processing exclusively in syntactic terms (e.g., by measuring Shannon entropy of sets of macromolecules), and abstract completely from semantic aspects that are related to the meaning of molecular information.

Methods

This mini-review focusses on semantic aspects of molecular information, particularly on codes that organize the semantic dimension of molecular information. First, a general conceptual framework for describing molecular information is proposed. Second, some examples of molecular codes are presented. Third, a mathematical approach that makes the identification of molecular codes in reaction networks possible, is developed.

Results

By combining a systematic conceptual framework for describing molecular information and a mathematical approach to identify molecular codes, it is possible to give a formally consistent and empirically adequate model of the code-based semantics of molecular information in cells.

General significance

Research on the semantics of molecular information is of great importance particularly to systems biology since molecular codes embedded in systems of interrelated codes govern main traits of cells. Describing cells as semantic systems may thus trigger new experiments and generate new insights into the fundamental processes of cellular information processing. This article is part of a Special Issue entitled Systems Biology of Microorganisms.     

Viscosimetric studies on molecular weight fractions of fulvic and humic acids of aquatic,terrestrial and microbial origin

Summary Viscosities were investigated of solutions of fulvic and humic acid molecular weight fractions of aquatic, terrestrial and microbial origin. Aquatic fulvic and humic acid molecules were, at pH 7, more voluminous than other types of humic compounds of similar molecular weight. It would appear that in low molecular weight non-aquatic humic matter, more inter- than intra-molecular bonding is present, with increasing molecular weight the bonding becomes more intra-molecular. Differences between average molecular weight values as obtained by an ultrafiltration method (Amicon) and by viscosimetry ranged from –18.7 to 18.5%. The largest deviations were in the low molecular weight range (<5,500 daltons). Higher molecular weight humics (in particular humic acids) appeared to have a more elongated structure than lower molecular weight material (in particular fulvic acids). Indications were obtained that on hydration humic moleculars become more elongated.     

Molecular clock mirages

The hypothesis of the molecular clock proposes that molecular evolution occurs at rates that persist through time and across lineages, for a given gene. The neutral theory of molecular evolution predicts that the clock will be a Poisson process, with equal mean and variance. Experimental data have shown that the variance is typically larger than the mean. Hypotheses have been advanced to account for the hypervariance of molecular evolution. Four recent papers show that none of the predictive hypotheses that have been proposed can be generally maintained. The conclusion is that molecular evolution is dependent on the fickle process of natural selection. But it is a time-dependent process, so that accumulation of empirical data often yields an approximate clock, as a consequence of the expected convergence of large numbers.     

Heterogeneous genomic molecular clocks in primates

Using data from primates, we show that molecular clocks in sites that have been part of a CpG dinucleotide in recent past (CpG sites) and non-CpG sites are of markedly different nature, reflecting differences in their molecular origins. Notably, single nucleotide substitutions at non-CpG sites show clear generation-time dependency, indicating that most of these substitutions occur by errors during DNA replication. On the other hand, substitutions at CpG sites occur relatively constantly over time, as expected from their primary origin due to methylation. Therefore, molecular clocks are heterogeneous even within a genome. Furthermore, we propose that varying frequencies of CpG dinucleotides in different genomic regions may have contributed significantly to conflicting earlier results on rate constancy of mammalian molecular clock. Our conclusion that different regions of genomes follow different molecular clocks should be considered when inferring divergence times using molecular data and in phylogenetic analysis.     

Reaction field method for the molecular orientation potential in an anisotropic medium

The molecular orientation potential in an anisotropic medium was studied using the reaction field method. The interaction energy between a molecule and an anisotropic medium was calculated using the dielectric anisotropy as a perturbation parameter. We have investigated the influence of molecular geometry on the molecular orientation potential using biphenyl and terphenyl, which constitute cores of liquid crystal molecules. We have calculated the barrier height for the molecular rotation changing the twist angle between phenyl rings, using anab initio molecular orbital method. We have found that the torsional motion of the phenyl rings affects the orientation potential, and that deviation from the molecular cylindrical symmetry lowers the saddle point for the rotation.