Compressed indexing and local alignment of DNA

MOTIVATION: Recent experimental studies on compressed indexes (BWT, CSA, FM-index) have confirmed their practicality for indexing very long strings such as the human genome in the main memory. For example, a BWT index for the human genome (with about 3 billion characters) occupies just around 1 G bytes. However, these indexes are designed for exact pattern matching, which is too stringent for biological applications. The demand is often on finding local alignments (pairs of similar substrings with gaps allowed). Without indexing, one can use dynamic programming to find all the local alignments between a text T and a pattern P in O(|T||P|) time, but this would be too slow when the text is of genome scale (e.g. aligning a gene with the human genome would take tens to hundreds of hours). In practice, biologists use heuristic-based software such as BLAST, which is very efficient but does not guarantee to find all local alignments. RESULTS: In this article, we show how to build a software called BWT-SW that exploits a BWT index of a text T to speed up the dynamic programming for finding all local alignments. Experiments reveal that BWT-SW is very efficient (e.g. aligning a pattern of length 3 000 with the human genome takes less than a minute). We have also analyzed BWT-SW mathematically for a simpler similarity model (with gaps disallowed), and we show that the expected running time is O(/T/(0.628)/P/) for random strings. As far as we know, BWT-SW is the first practical tool that can find all local alignments. Yet BWT-SW is not meant to be a replacement of BLAST, as BLAST is still several times faster than BWT-SW for long patterns and BLAST is indeed accurate enough in most cases (we have used BWT-SW to check against the accuracy of BLAST and found that only rarely BLAST would miss some significant alignments). AVAILABILITY: www.cs.hku.hk/~ckwong3/bwtsw CONTACT: twlam@cs.hku.hk.     

Relatedness and other finescale population genetic analyses in the threatened eastern box turtle (Terrapene c. carolina) suggest unexpectedly high vagility with important conservation implications

Genetic analyses of populations are essential to the conservation of threatened and cryptic taxa such as Chelonians. Turtles and tortoises are among the most imperiled vertebrate taxa worldwide, yet many of the natural history traits remain unknown leaving management decisions ill- or improperly informed. The eastern box turtle Terrapene c. carolina is no exception, with many gaps in our knowledge about traits such as juvenile dispersal and patterns of relatedness across the landscape, especially as it is a species not particularly tied to water and vulnerable to human disturbance. In addition, all long-term studies of this species have documented demographic population declines, even in protected habitats. In this study we explore finescale population structuring, gene flow, dispersal, and relatedness at four sites across the species range. These sites vary in habitat fragmentation and surrounding habitat quality. Many radiotelemtery and mark-recapture studies suggest that Terrapene spp. have a sedentary natural history, with small and temporally conserved home ranges and little propensity for dispersal. Based on these data we predicted that populations would be highly structured at fine geographic scales, closely related individuals (1st- and 2nd-degree relatives) would coexist in close proximity, and individuals exhibiting transient behavior would be true transients. All sites had low levels of population structuring, mean pairwise relatedness values were statistically zero, over 90 % of pairs of individuals were unrelated, 4.4–8.7 % were half-siblings, and fewer than 1.0 % were full siblings or parent-offspring pairs. These patterns were consistent across all four sites, regardless of habitat fragmentation. Furthermore, while some related pairs were found within a few meters of each other, others ranged up to 33 km apart. We found that one of two individuals with transient behavior was indeed a true genetic transient. These findings suggest that box turtles may be much more vagile than current management practices recognize. As most turtle species are strongly affected by anthropogenic disturbance, many may require much larger contiguous blocks of intact habitat for species persistence as the box turtle likely does. Management plans may therefore need to be updated to allow for safe and effective long-distance dispersal at the appropriate spatial scales in order to maintain genetic health of these species.     

A cladistic analysis of wax scales (Hemiptera: Coccoidea: Coccidae: Ceroplastinae)

Seven genera of wax scales (Ceroplastinae) have been accepted as valid by some or all coecidologists: Ceroplastes Gray, Ceroplastidia Cockerell, Cerostegia De Lotto, Gascardia Targioni Tozzetti, Paracerostegia Tang, Vinsonia Signoret and Waxiella De Lotto. The status of most these genera is controversial. The present study reviews the taxonomic history of wax scales and presents a new classification based on cladistic analysis of morphological data from the adult females of eighty-three species. The analysis indicates that the wax scales form a monophyletic group, that Waxiella is monophyletic but that Ceroplastidia, Gascardia and Vinsonia are not, and fails to support the generic status of Cerostegia and Paracerostegia. Apart from the type species of Vinsonia , which was placed as a sister to the rest of wax scales, the only other species assigned to Vinsonia and most species of all other genera fall within Ceroplastes in the cladogram. Recognition of any of these genera renders Ceroplastes paraphyletic or polyphyletic. Thus, cladistically, the wax scales should be classified into one genus, Ceroplastes.     

The use of genetically engineered mouse models of prostate cancer for nutrition and cancer chemoprevention research

The ability to modify the expression of specific genes in the mouse through genetic engineering technologies allows for the generation of previously unavailable models for prostate cancer prevention research. Although animal models have existed for some time for the study of prostate cancer prevention (primarily in the rat), it is uncertain if the mechanisms that drive prostate carcinogenesis in these models are relevant to those in human prostate cancer. Cell culture studies are of limited usefulness because the conditions are inherently artificial. Factors such as relevant physiologic concentrations and metabolism of putative chemoprevention compounds are difficult to model in an in vitro system. These studies also preclude the types of interactions known to occur between multiple cell types in vivo. In addition, all prostate cancer cell lines are already highly progressed and are not representative of the type of cells to which most preventive strategies would be targeted. Due to the advent of genetically engineered mouse (GEM) models, we now have models of prostate cancer that are dependent on molecular mechanisms already implicated in human prostate carcinogenesis. With these models we can perform a variety of experiments that could previously only be done in cell culture or in prostate cancer cell line xenografts. The currently available GEM models of prostate cancer have been extensively reviewed therefore, this review will focus on the types of models available and their usefulness for various types of preclinical studies relevant to prostate cancer prevention.     

Biodiversity monitoring: some proposals to adequately study species’ responses to climate change

Climate change affects all levels of biology and is a major threat for biodiversity. Hence, it is fundamental to run biodiversity monitoring programs to understand the effects of climate change on the biota and to be able to adjust management and conservation accordingly. So far, however, very few existing monitoring programs allow for the detection of climate change effects, as shown by a survey undertaken by the European project EuMon. Despite this shortcoming, several methods exist which allow to make inferences from existing data by integrating data across different monitoring programs: correlative analyses, meta-analyses and models. In addition, experiments are thought to be useful tools to understand the effects of climate change on plants and animals. Here, we evaluate the utility of these four main approaches. All these methods allow to evaluate long term effects of climate change and make predictions of species’ future development, but they are arguable. We list and compare their benefits and inconveniences, which can lead to uncertainties in the extrapolation of species responses to global climate change. Individual characteristics and population parameters have to be more frequently monitored. The potential evolution of a species should be also modelled, to extrapolate results across spatial and temporal scales as well as to analyse the combined effects of different climatic and biotic factors, including intra but also interspecific relationships. We conclude that a combination of methodologies would be the most promising tool for the assessment of biological responses to climate change, and we provide some thoughts about how to do so. Particularly, we encourage long-term studies along natural gradients (altitudinal or latitudinal) on the same species/habitats to be able to extrapolate to large geographic scales, and to have more complete data sets, necessary to understand the mechanisms of responses. Such data may provide a more accurate base for simulations across spatial and temporal scales, especially if they are publicly available in a common database. These recommendations could allow the adaptation of species management and the development of conservation tools to climate change which threatens species.     

Biological implications of isochore boundaries in the human genome

The human genome is composed of large sequence segments with fairly homogeneous GC content, namely isochores, which have been linked to many important functions; biological implications of most isochore boundaries, however, remain elusive, partly due to the difficulty in determining these boundaries at high resolution. Using the segmentation algorithm based on the quadratic divergence, we re-determined all 79 boundaries of previously identified human isochores at single-nucleotide resolution, and then compared the boundary coordinates with other genome features. We found that 55.7% of isochore boundaries coincide with termini of repeat elements; 45.6% of isochore boundaries coincide with termini of highly conserved sequences based on alignment of 17 vertebrate genomes, i.e., the highly conserved genome sequence switches to a less or non-conserved one at the isochore boundary; some isochore boundaries coincide with abrupt change of CpG island distribution (note that one boundary can associate with more than one genome feature). In addition, sequences around isochore boundaries are highly conserved. It seems reasonable to deduce that the boundaries of all the isochores studied here would be replication timing sites in the human genome. These results suggest possible key roles of the isochore boundaries and may further our understanding of the human genome organization.     

Human activities change marine ecosystems by altering predation risk

In ocean ecosystems, many of the changes in predation risk – both increases and decreases – are human‐induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk‐based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human‐caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises.     

Anthropogenic environments exert variable selection on cranial capacity in mammals

It is thought that behaviourally flexible species will be able to cope with novel and rapidly changing environments associated with human activity. However, it is unclear whether such environments are selecting for increases in behavioural plasticity, and whether some species show more pronounced evolutionary changes in plasticity. To test whether anthropogenic environments are selecting for increased behavioural plasticity within species, we measured variation in relative cranial capacity over time and space in 10 species of mammals. We predicted that urban populations would show greater cranial capacity than rural populations and that cranial capacity would increase over time in urban populations. Based on relevant theory, we also predicted that species capable of rapid population growth would show more pronounced evolutionary responses. We found that urban populations of two small mammal species had significantly greater cranial capacity than rural populations. In addition, species with higher fecundity showed more pronounced differentiation between urban and rural populations. Contrary to expectations, we found no increases in cranial capacity over time in urban populations—indeed, two species tended to have a decrease in cranial capacity over time in urban populations. Furthermore, rural populations of all insectivorous species measured showed significant increases in relative cranial capacity over time. Our results provide partial support for the hypothesis that urban environments select for increased behavioural plasticity, although this selection may be most pronounced early during the urban colonization process. Furthermore, these data also suggest that behavioural plasticity may be simultaneously favoured in rural environments, which are also changing because of human activity.     

The relationship between multi‐scale habitat heterogeneity and farmland bird abundance

It has recently been proposed that losses in farmland habitat heterogeneity may have been a primary driver of the profound declines exhibited by many farmland bird species in recent decades. However, it has yet to be demonstrated which facets of heterogeneity and what spatial scales are most important for birds. Here we analyse the relationship between abundance and features of landscape heterogeneity at three spatial scales (1, 9 and 25 km²) for 32 bird species commonly associated with farmland. Heterogeneity was quantified using three contrasting indices reflecting 1) the spatial mixing of land uses, 2) variation in field sizes and 3) the density of field boundaries. The spatial mixing of land‐uses explained, on average, the most variation in, and was most likely to be positively associated with, abundance at all spatial scales. The majority of species (66–75%, depending on the spatial scale) were more common in heterogeneous landscapes overall; however, migrants, those under a high level of conservation concern and farmland specialist species tended to be less abundant in more heterogeneous landscapes at all scales. Ground‐nesting species were also more likely to be found in more homogeneous habitats than non‐ground‐nesters, but only at the finest spatial scale. Relationships between abundance and heterogeneity were generally consistent across spatial scales; however, species of high conservation concern had more variable associations compared with other species. These results highlight a potential role for farmland habitat heterogeneity in determining the abundance of many farmland species but suggest that population responses to an increase in heterogeneity would not be unanimously positive and would probably have negative impacts on some species, notably those that are already threatened.     

Gene‐flow across the European crow hybrid zone – a spatial simulation

In hybrid zones populations that are otherwise allopatric meet and produce hybrids. One of the most well‐known hybrid zones occurs throughout much of Europe between the hooded and carrion crows. Even though these species (or subspecies) of crows look very different, genetic differentiation is weak, and introgression seems to be common. In a spatial simulation that was based on empirically estimated values, we investigated how introgressing alleles that would confer some fitness advantage would flow across the zone. The advantage was assumed to be some unknown factor that enhanced survival for carriers relative to non‐carriers. We varied the yearly survival advantage between 0 to 10% and recorded how this would affect zone shape and position. In the simulation we cycled ‘yearly’ events such as reproduction, mortality and juvenile dispersal. We started the simulation by equipping all individuals of one crow type outside the zone with a homozygotic set of the beneficial allele. At all levels of advantage the allele first rapidly became fixed in the donator crow type, then transgressed into the receiving type more slowly and finally became fixed in all individuals. The time until fixation varied from around 176 yr for a 10% advantage to around 20 000 yr for 0% advantage. An exciting discovery was that the position of the zone would move during the introgression but then stop. The reason is that the beneficial allele would be common in the donating type but not in the receiving type during the introgression event. At large the crow hybrid zone appears to have been stable for a long time but there have been small recent northward movements of carrion crows in both Scotland and Denmark. We suggest that introgression by itself is a factor that should be considered as an explanation for why hybrid zones move temporarily.     

Consequences of the Armed Conflict, Forced Human Displacement, and Land Abandonment on Forest Cover Change in Colombia: A Multi-scaled Analysis

Most studies of land change have focused on patterns, rates, and drivers of deforestation, but much less is known about the dynamics associated with agricultural abandonment and ecosystem recovery. Furthermore, most studies are conducted at a single spatial scale, and few have included variables related with internal socio-political conflicts. Here we evaluated the effect of environmental, demographic, and socio-economic variables on woody cover change in Colombia between 2001 and 2010 at the country, biome, and ecoregion scales. We also incorporated factors that reflect the unique history of Colombia such as the presence of illegal-armed groups and forced human displacement. Environmental variables explained the patterns of deforestation and forest regrowth at all scales because they can restrict or encourage different land uses across multiple spatial scales. Demographic variables were important at the biome and ecoregion scales and appear to be a consequence of the armed conflict, particularly through forced human displacement (for example, rural–urban migration), which in some areas has resulted in forest regrowth. In other areas, the impact of illegal armed groups has reduced forest cover, particularly in areas rich in gold and lands appropriate for cattle grazing. This multi-scale and multivariate approach provides a new insight into the complex relationship between woody cover change and land abandonment triggered mainly by armed conflict.     

Photographic identification of individual grayling, Thymallus thymallus, based on the disposition of black dots and scales

SUMMARY. The flanks of grayling are generally studded with black dots which vary in number. The number and position of these dots are well-defined for each individual and make it possible to identify each fish, in some cases, as when there are very few dots or none at all, it is necessary to make use of other features such as the general disposition of the scales.
The best method for recording these characters is by photographing each fish. When recaptured, a fish can be recognized by comparing photographs. The number and position of dots on their lines can be sorted by a computer. Ultimate confirmation is given by comparing the most likely photographs once they have been selected by the computer.     

The evolutionary origin of feathers.

Previous theories relating the origin of feathers to flight or to heat conservation are considered to be inadequate. There is need for a model of feather evolution that gives attention to the function and adaptive advantage of intermediate structures. The present model attempts to reveal and to deal with, the spectrum of complex questions that must be considered. In several genera of modern lizards, scales are elongated in warm climates. It is argued that these scales act as small shields to solar radiation. Experiments are reported that tend to confirm this. Using lizards as a conceptual model, it is argued that feathers likewise arose as adaptations to intense solar radiation. Elongated scales are assumed to have subdivided into finely branched structures that produced a heat-shield, flexible as well as long and broad. Associated muscles had the function of allowing the organism fine control over rates of heat gain and loss: the specialized scales or early feathers could be moved to allow basking in cool weather or protection in hot weather. Subdivision of the scales also allowed a close fit between the elements of the insulative integument. There would have been mechanical and thermal advantages to having branches that interlocked into a pennaceous structure early in evolution, so the first feathers may have been pennaceous. A versatile insulation of movable, branched scales would have been a preadaptation for endothermy. As birds took to the air they faced cooling problems despite their insulative covering because of high convective heat loss. Short glides may have initially been advantageous in cooling an animal under heat stress, but at some point the problem may have shifted from one of heat exclusion to one of heat retention. Endothermy probably evolved in conjunction with flight. If so, it is an unnecessary assumption to postulate that the climate cooled and made endothermy advantageous. The development of feathers is complex and a model is proposed that gives attention to the fundamental problems of deriving a branched structure with a cylindrical base from an elongated scale.     

Spatial analyses of intertidal assemblages on sheltered rocky shores

Abstract Understanding processes in complex assemblages depends on good understanding of spatial and temporal patterns of structure at various spatial scales. There has been little quantitative information about spatial patterns and natural temporal changes in intertidal assemblages on sheltered rocky shores in temperate Australia. Natural changes and responses to anthropogenic disturbances in these habitats cannot be accurately measured and assessed without quantitative data on patterns of natural variability in space and through time. This paper describes some suitable quantitative methods for examining spatial and temporal patterns of diversity and abundances of highshore, midshore and lowshore intertidal assemblages and the important component species for a number of shores in a bay that has not been severely altered by human disturbance. Despite a diverse flora and fauna on these shores, the midshore and lowshore assemblages on sheltered shores were characterized by a few species which were also the most important in discriminating among assemblages on a shore and, for each assemblage, among different shores. The same set of species was also important for measuring small-scale patchiness within each assemblage (i.e. between replicate sites on a shore). Therefore, these data provide a rationale for selecting species that are useful for measuring differences and changes in abundance among places and times at different scales and, hence, can be used in the more complex sampling designs necessary to detect environmental impacts. There was considerable spatial variability in all assemblages and all species (or taxa) examined at scales of metres, tens of metres and kilometres. There were no clear seasonal trends for most measures, with as much or more variability at intervals of 3 months as from year to year. Most interactions between spatial and temporal measures were at the smallest scale, with different sites on the same shore generally showing different changes from time to time. The cause(s) of this apparently idiosyncratic variability1 were not examined, but some potential causes are discussed. These data are appropriate for testing hypotheses about the applicability of these findings to other relatively undisturbed sheltered shores, about effects of different anthropogenic disturbances on sheltered intertidal assemblages and to test hypotheses about differences in intertidal assemblages on sheltered versus wave-exposed shores.     

Recombinant protein production and streptomycetes

The biopharmaceutical market has come a long way since 1982, when the first biopharmaceutical product, recombinant human insulin, was launched. Just over 200 biopharma products have already gained approval. The global market for biopharmaceuticals which is currently valued at over US$99 billion has been growing at an impressive compound annual growth rate over the previous years. To produce these biopharmaceuticals and other industrially important heterologous proteins, different prokaryotic and eukaryotic expression systems are used. All expression systems have some advantages as well as some disadvantages that should be considered in selecting which one to use. Choosing the best one requires evaluating the options--from yield to glycosylation, to proper folding, to economics of scale-up. No host cell from which all the proteins can be universally expressed in large quantities has been found so far. Therefore, it is important to provide a variety of host-vector expression systems in order to increase the opportunities to screen for the most suitable expression conditions or host cell. In this overview, we focus on Streptomyces lividans, a Gram-positive bacterium with a proven excellence in secretion capacity, as host for heterologous protein production. We will discuss its advantages and disadvantages, and how with systems biology approaches strains can be developed to better producing cell factories.     

Reduction of slow-fast asymptotically autonomous systems with applications to gradostat models

Two distinguishing features characterize the population dynamic models considered in the present work. On the one hand, we consider several interacting organization levels associated to different time scales. On the other hand, the environment tends to be constant in the long term. The mathematical representation of these properties leads to slow-fast asymptotically autonomous systems. These characteristics add some realism in the models. However, the analytical study of this class of systems is generally hard to perform.Here we present a reduction technique that can be included among the so-called approximate aggregation methods. The existence of different time scales, together with the long term features, are used to build up a simpler system, which can be described by means of a lower number of state variables. The asymptotic behavior of the simplified model helps to study the original one.The reduction procedure is formulated in a general way. Following, two illustrations of asymptotically autonomous models with two time scales, in a gradostat, are given: a consumer–resource model and a competition model. Finally, a wider range of applications is suggested.     

Biological Implications of Isochore Boundaries in the Human Genome

Abstract

The human genome is composed of large sequence segments with fairly homogeneous GC content, namely isochores, which have been linked to many important functions; biological implications of most isochore boundaries, however, remain elusive, partly due to the difficulty in determining these boundaries at high resolution. Using the segmentation algorithm based on the quadratic divergence, we re-determined all 79 boundaries of previously identified human isochores at single-nucleotide resolution, and then compared the boundary coordinates with other genome features. We found that 55.7% of isochore boundaries coincide with termini of repeat elements; 45.6% of isochore boundaries coincide with termini of highly conserved sequences based on alignment of 17 vertebrate genomes, i.e., the highly conserved genome sequence switches to a less or non-conserved one at the isochore boundary; some isochore boundaries coincide with abrupt change of CpG island distribution (note that one boundary can associate with more than one genome feature). In addition, sequences around isochore boundaries are highly conserved. It seems reasonable to deduce that the boundaries of all the isochores studied here would be replication timing sites in the human genome. These results suggest possible key roles of the isochore boundaries and may further our understanding of the human genome organization.     

Long- and short-range interactions in native protein structures are consistent/minimally frustrated in sequence space

We show that long- and short-range interactions in almost all protein native structures are actually consistent with each other for coarse-grained energy scales; specifically we mean the long-range inter-residue contact energies and the short-range secondary structure energies based on peptide dihedral angles, which are potentials of mean force evaluated from residue distributions observed in protein native structures. This consistency is observed at equilibrium in sequence space rather than in conformational space. Statistical ensembles of sequences are generated by exchanging residues for each of 797 protein native structures with the Metropolis method. It is shown that adding the other category of interaction to either the short- or long-range interactions decreases the means and variances of those energies for essentially all protein native structures, indicating that both interactions consistently work by more-or-less restricting sequence spaces available to one of the interactions. In addition to this consistency, independence by these interaction classes is also indicated by the fact that there are almost no correlations between them when equilibrated using both interactions and significant but small, positive correlations at equilibrium using only one of the interactions. Evidence is provided that protein native sequences can be regarded approximately as samples from the statistical ensembles of sequences with these energy scales and that all proteins have the same effective conformational temperature. Designing protein structures and sequences to be consistent and minimally frustrated among the various interactions is a most effective way to increase protein stability and foldability.