Opsins: Evolution in waiting

Complete vertebrate genome sequencing has revealed a remarkable stability and uniformity in the protein-coding gene set, which at first glance might suggest that gene duplication events are relatively rare. This may be a red herring, or at least a red cichlid, as the Lake Malawi cichlid fishes show rapid and extensive duplication and diversification of their retinal cone photoreceptor opsin genes.

Accelerating, hyperaccelerating, and decelerating networks

Many growing networks possess accelerating statistics where the number of links added with each new node is an increasing function of network size so the total number of links increases faster than linearly with network size. In particular, biological networks can display a quadratic growth in regulator number with genome size even while remaining sparsely connected. These features are mutually incompatible in standard treatments of network theory which typically require that every new network node possesses at least one connection. To model sparsely connected networks, we generalize existing approaches and add each new node with a probabilistic number of links to generate either accelerating, hyperaccelerating, or even decelerating network statistics in different regimes. Under preferential attachment for example, slowly accelerating networks display stationary scale-free statistics relatively independent of network size while more rapidly accelerating networks display a transition from scale-free to exponential statistics with network growth. Such transitions explain, for instance, the evolutionary record of single-celled organisms which display strict size and complexity limits.

Novel mitochondrial gene content and gene arrangement indicate illegitimate inter-mtDNA recombination in the chigger mite, Leptotrombidium pallidum

To better understand the evolution of mitochondrial (mt) genomes in the Acari (mites and ticks), we sequenced the mt genome of the chigger mite, Leptotrombidium pallidum (Arthropoda: Acari: Acariformes). This genome is highly rearranged relative to that of the hypothetical ancestor of the arthropods and the other species of Acari studied. The mt genome of L. pallidum has two genes for large subunit rRNA, a pseudogene for small subunit rRNA, and four nearly identical large noncoding regions. Nineteen of the 22 tRNAs encoded by this genome apparently lack either a T-arm or a D-arm. Further, the mt genome of L. pallidum has two distantly separated sections with identical sequences but opposite orientations of transcription. This arrangement cannot be accounted for by homologous recombination or by previously known mechanisms of mt gene rearrangement. The most plausible explanation for the origin of this arrangement is illegitimate inter-mtDNA recombination, which has not been reported previously in animals. In light of the evidence from previous experiments on recombination in nuclear and mt genomes of animals, we propose a model of illegitimate inter-mtDNA recombination to account for the novel gene content and gene arrangement in the mt genome of L. pallidum.

Inherent size constraints on prokaryote gene networks due to "accelerating" growth

Networks exhibiting accelerating growth have total link numbers growing faster than linearly with network size and either reach a limit or exhibit graduated transitions from nonstationary-to-stationary statistics and from random to scale-free to regular statistics as the network size grows. However, if for any reason the network cannot tolerate such gross structural changes then accelerating networks are constrained to have sizes below some critical value. This is of interest as the regulatory gene networks of single-celled prokaryotes are characterized by an accelerating quadratic growth and are size constrained to be less than about 10,000 genes encoded in DNA sequence of less than about 10 megabases. This paper presents a probabilistic accelerating network model for prokaryotic gene regulation which closely matches observed statistics by employing two classes of network nodes (regulatory and non-regulatory) and directed links whose inbound heads are exponentially distributed over all nodes and whose outbound tails are preferentially attached to regulatory nodes and described by a scale-free distribution. This model explains the observed quadratic growth in regulator number with gene number and predicts an upper prokaryote size limit closely approximating the observed value. (c) 2005 Elsevier GmbH. All rights reserved.

Evolution of duplicate control regions in the mitochondrial genomes of metazoa: A case study with Australasian Ixodes ticks

To investigate the evolution pattern and phylogenetic utility of duplicate control regions (CRs) in mitochondrial (mt) genomes, we sequenced the entire mt genomes of three Ixodes species and part of the mt genomes of another I I species. All the species from the Australasian lineage have duplicate CRs, whereas the other species have one CR. Sequence analyses indicate that the two CRs of the Australasian Ixodes ticks have evolved in concert in each species. In addition to the Australasian Ixodes ticks, species from seven other lineages of metazoa also have mt genomes with duplicate CRs. Accumulated mtDNA sequence data from these metazoans and two recent experiments on replication of mt genomes in human cell lines with duplicate CRs allowed us to re-examine four intriguing questions about the presence of duplicate CRs in the mt genomes of metazoa: (1) Why do some mt genomes, but not others, have duplicate CRs? (2) How did mt genomes with duplicate CRs evolve? (3) How could the nucleotide sequences of duplicate CRs remain identical or very similar over evolutionary time? (4) Are duplicate CRs phylogenetic markers? It appears that mt genomes with duplicate CRs have a selective advantage in replication over mt genomes with one CR. Tandem duplication followed by deletion of genes is the most plausible mechanism for the generation of mt genomes with duplicate CRs. Once duplicate CRs occur in an mt genome, they tend to evolve in concert, probably by gene conversion. However, there are lineages where gene conversion may not always occur, and, thus, the two CRs may evolve independently in these lineages. Duplicate CRs have much potential as phylogenetic markers at low taxonomic levels, such as within genera, within families, or among families, but not at high taxonomic levels, such as among orders.

An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: Relationship to cystatins and the tumor suppressor TIG1

Latexin, the only known mammalian carboxypeptidase inhibitor, has no detectable sequence similarity with plant and parasite inhibitors, but it is related to a human putative tumor suppressor protein, TIG1. Latexin is expressed in the developing brain, and we find that it plays a role in inflammation, as it is expressed at high levels and is inducible in macrophages in concert with other protease inhibitors and potential protease targets. The crystal structure of mouse latexin, solved at 1.83 Angstrom resolution, shows no structural relationship with other carboxypeptidase inhibitors. Furthermore, despite a lack of detectable sequence duplication, the structure incorporates two topologically analogous domains related by pseudo two-fold symmetry. Surprisingly, these domains share a cystatin fold architecture found in proteins that inhibit cysteine proteases, suggesting an evolutionary and possibly functional relationship. The structure of the tumor suppressor protein TIG1 was modeled, revealing its putative membrane binding surface.

The crystal structure of a bacterial Class II ketol-acid reductolsomerase: Domain conservation and evolution

Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes two steps in the biosynthesis of branched-chain amino acids. Amino acid sequence comparisons across species reveal that there are two types of this enzyme: a short form (Class 1) found in fungi and most bacteria, and a long form (Class 11) typical of plants. Crystal structures of each have been reported previously. However, some bacteria such as Escherichia coli possess a long form, where the amino acid sequence differs appreciably from that found in plants. Here, we report the crystal structure of the E. coli enzyme at 2.6 A resolution, the first three-dimensional structure of any bacterial Class 11 KARI. The enzyme consists of two domains, one with mixed alpha/beta structure, which is similar to that found in other pyridine nucleotide-dependent dehydrogenases. The second domain is mainly alpha-helical and shows strong evidence of internal duplication. Comparison of the active sites between KARI of E. coli, Pseudomonas aeruginosa, and spinach shows that most residues occupy conserved positions in the active site. E. coli KARI was crystallized as a tetramer, the likely biologically active unit. This contrasts with P. aeruginosa KARI, which forms a dodecamer, and spinach KARI, a dimer. In the E. coli KARI tetramer, a novel subunit-to-subunit interacting surface is formed by a symmetrical pair of bulbous protrusions.

Endangered ancestress revisited: Sarah's miraculous motherhood and the restoration of Eden

The paper examines the ‘endangered ancestress’ theme in Genesis, in which the matriarchs, Sarah and Rebecca, are passed off to alien rulers as the sisters of their respective husbands, in Sarah’s case twice. Rather than viewing these incidents as clumsy duplication, the paper reads them as a literary device in a continuous narrative. The paper argues that when read in this way, these incidents serve to underline the singular status of Sarah in contrast to Rebecca and subsequent matriarchs. Sarah is shown to be the unique foremother of Israel. Alone of all her sex, she represents a pristine new beginning, analogous to human beginnings in Eden.

A novel carbonic anhydrase from the giant clam Tridacna gigas contains two carbonic anhydrase domains

This report describes the presence of a unique dual domain carbonic anhydrase (CA) in the giant clam, Tridacna gigas. CA plays an important role in the movement of inorganic carbon (C-i) from the surrounding seawater to the symbiotic algae that are found within the clam's tissue. One of these isoforms is a glycoprotein which is significantly larger (70 kDa) than any previously reported from animals (generally between 28 and 52 kDa). This alpha-family CA contains two complete carbonic anhydrase domains within the one protein, accounting for its large size; dual domain CAs have previously only been reported from two algal species. The protein contains a leader sequence, an N-terminal CA domain and a C-terminal CA domain. The two CA domains have relatively little identity at the amino acid level (29%). The genomic sequence spans in excess of 17 kb and contains at least 12 introns and 13 exons. A number of these introns are in positions that are only found in the membrane attached/secreted CAs. This fact, along with phylogenetic analysis, suggests that this protein represents the second example of a membrane attached invertebrate CA and it contains a dual domain structure unique amongst all animal CAs characterized to date.

Molecular mechanisms for the variation of mitochondrial gene content and gene arrangement among chigger mites of the genus Leptotrombidium (Acari : Acariformes)

The gene content of a mitochondrial (mt) genome, i.e., 37 genes and a large noncoding region (LNR), is usually conserved in Metazoa. The arrangement of these genes and the LNR is generally conserved at low taxonomic levels but varies substantially at high levels. We report here a variation in mt gene content and gene arrangement among chigger mites of the genus Leptotrombidium. We found previously that the mt genome of Leptotrombidium pallidum has an extra gene for large-subunit rRNA (rrnL), a pseudo-gene for small-subunit rRNA (PrrnS), and three extra LNRs, additional to the 37 genes and an LNR typical of Metazoa. Further, the arrangement of mt genes of L. pallidum differs drastically from that of the hypothetical ancestor of the arthropods. To find to what extent the novel gene content and gene arrangement occurred in Leptotrombidium, we sequenced the entire or partial mt genomes of three other species, L. akamushi, L. deliense, and L. fletcheri. These three species share the arrangement of all genes with L. pallidum, except trnQ (for tRNA-glutamine). Unlike L. pallidum, however, these three species do not have extra rrnL or PrrnS and have only one extra LNR. By comparison between Leptotrombidium species and the ancestor of the arthropods, we propose that (1) the type of mt genome present in L. pallidum evolved from the type present in the other three Leptotrombidium species, and (2) three molecular mechanisms were involved in the evolution of mt gene content and gene arrangement in Leptotrombidium species.

Medication management at home: medication risk factor prevalence and inter-relationships

Background and objective: Patients can have medication-related risk factors associated with poor health outcomes that become evident through visiting them in their homes. These medication-related risk factors may not be apparent in pharmacy and general practitioner (GP) records. The aim was to determine the prevalence and inter-relationships of medication-related risk factors for poor patient health outcomes identifiable through 'in-home' observations. Methods: The design was a cross-sectional study of 204 general practice patients living in their own homes and at risk of medication-related poor health outcomes. Medication-related risk factors were identified in the patients' homes by community pharmacists and GPs. Results and discussion: The prevalence of risk factors varied from 8.3% (multiple medication storage locations) to 55.9% (confused by generic and trade names). There were many relationships observed between the medication-related risk factors, with expired medication having the most relationships with other risk factors followed by therapeutic duplication and poor adherence (9, 6 and 6 relationships respectively). Conclusion: Visiting patients' homes may identify medication-related risk factors not otherwise apparent through patient visits to the health practitioner when medications may be brought for review (i.e. 'brown bag' reviews).

Integration of ice-core, marine and terrestrial records for the Australian Last Glacial Maximum and Termination: a contribution from the OZ INTIMATE group

The degree to which Southern Hemisphere climatic changes during the end of the last glacial period and early Holocene (30-8 ka) were influenced or initiated by events occurring in the high latitudes of the Northern Hemisphere is a complex issue. There is conflicting evidence for the degree of hemispheric 'teleconnection' and an unresolved debate as to the principle forcing mechanism(s). The available hypotheses are difficult to test robustly, however, because the few detailed palaeoclimatic records in the Southern Hemisphere are widely dispersed and lack duplication. Here we present climatic and environmental reconstructions from across Australia, a key region of the Southern Hemisphere because of the range of environments it covers and the potentially important role regional atmospheric and oceanic controls play in global climate change. We identify a general scheme of events for the end of the last glacial period and early Holocene but a detailed reconstruction proved problematic. Significant progress in climate quantification and geochronological control is now urgently required to robustly investigate change through this period. Copyright (c) 2006 John Wiley & Sons, Ltd.

Towards platform-independent real-time systems

Real-time software systems are rarely developed once and left to run. They are subject to changes of requirements as the applications they support expand, and they commonly outlive the platforms they were designed to run on. A successful real-time system is duplicated and adapted to a variety of applications - it becomes a product line. Current methods for real-time software development are commonly based on low-level programming languages and involve considerable duplication of effort when a similar system is to be developed or the hardware platform changes. To provide more dependable, flexible and maintainable real-time systems at a lower cost what is needed is a platform-independent approach to real-time systems development. The development process is composed of two phases: a platform-independent phase, that defines the desired system behaviour and develops a platform-independent design and implementation, and a platform-dependent phase that maps the implementation onto the target platform. The last phase should be highly automated. For critical systems, assessing dependability is crucial. The partitioning into platform dependent and independent phases has to support verification of system properties through both phases.

Heuristic algorithm for computing reversal distance with multigene families via binary integer programming

Hannenhalli and Pevzner developed the first polynomial-time algorithm for the combinatorial problem of sorting of signed genomic data. Their algorithm solves the minimum number of reversals required for rearranging a genome to another when gene duplication is nonexisting. In this paper, we show how to extend the Hannenhalli-Pevzner approach to genomes with multigene families. We propose a new heuristic algorithm to compute the reversal distance between two genomes with multigene families via the concept of binary integer programming without removing gene duplicates. The experimental results on simulated and real biological data demonstrate that the proposed algorithm is able to find the reversal distance accurately. ©2005 IEEE

The emergence of order in random walk resource discovery protocols

While others have attempted to determine, by way of mathematical formulae, optimal resource duplication strategies for random walk protocols, this paper is concerned with studying the emergent effects of dynamic resource propagation and replication. In particular, we show, via modelling and experimentation, that under any given decay (purge) rate the number of nodes that have knowledge of particular resource converges to a fixed point or a limit cycle. We also show that even for high rates of decay - that is, when few nodes have knowledge of a particular resource - the number of hops required to find that resource is small.