Domain Evolution of Vertebrate Blood Coagulation Cascade Proteins.

Vertebrate blood coagulation is controlled by a cascade containing more than 20 proteins. The cascade proteins are found in the blood in their zymogen forms and when the cascade is triggered by tissue damage, zymogens are activated and in turn activate their downstream proteins by serine protease activity. In this study, we examined proteomes of 21 chordates, of which 18 are vertebrates, to reveal the modular evolution of the blood coagulation cascade.

The modular nature of protein evolution: domain rearrangement rates across eukaryotic life.

Background: Modularity is important for evolutionary innovation. The recombination of existing units to form larger complexes with new functionalities spares the need to create novel elements from scratch. In proteins, this principle can be observed at the level of protein domains, functional subunits which are regularly rearranged to acquire new functions.

DOGMA: a web server for proteome and transcriptome quality assessment.

Even in the era of next generation sequencing, in which bioinformatics tools abound, annotating transcriptomes and proteomes remains a challenge. This can have major implications for the reliability of studies based on these datasets. Therefore, quality assessment represents a crucial step prior to downstream analyses on novel transcriptomes and proteomes.

A Roadmap to Domain Based Proteomics.

Protein domains are reusable segments of proteins and play an important role in protein evolution. By combining the elements from a relatively small set of domains into unique arrangements, a large number of distinct proteins can be generated. Since domains often have specific functions, changes in their arrangement usually affect the overall protein function.

Remodeling of the juvenile hormone pathway through caste-biased gene expression and positive selection along a gradient of termite eusociality.

The evolution of division of labor between sterile and fertile individuals represents one of the major transitions in biological complexity. A fascinating gradient in eusociality evolved among the ancient hemimetabolous insects, ranging from noneusocial cockroaches through the primitively social lower termites-where workers retain the ability to reproduce-to the higher termites, characterized by lifetime commitment to worker sterility. Juvenile hormone (JH) is a prime candidate for the regulation of reproductive division of labor in termites, as it plays a key role in insect postembryonic development and reproduction.

DOGMA: domain-based transcriptome and proteome quality assessment.

Motivation: Genome studies have become cheaper and easier than ever before, due to the decreased costs of high-throughput sequencing and the free availability of analysis software. However, the quality of genome or transcriptome assemblies can vary a lot. Therefore, quality assessment of assemblies and annotations are crucial aspects of genome analysis pipelines.

Multiple sequence alignment modeling: methods and applications.

This review provides an overview on the development of Multiple sequence alignment (MSA) methods and their main applications. It is focused on progress made over the past decade. The three first sections review recent algorithmic developments for protein, RNA/DNA and genomic alignments.

How Do Genomes Create Novel Phenotypes? Insights from the Loss of the Worker Caste in Ant Social Parasites.

A central goal of biology is to uncover the genetic basis for the origin of new phenotypes. A particularly effective approach is to examine the genomic architecture of species that have secondarily lost a phenotype with respect to their close relatives. In the eusocial Hymenoptera, queens and workers have divergent phenotypes that may be produced via either expression of alternative sets of caste-specific genes and pathways or differences in expression patterns of a shared set of multifunctional genes.

Domain similarity based orthology detection.

Background: Orthologous protein detection software mostly uses pairwise comparisons of amino-acid sequences to assert whether two proteins are orthologous or not. Accordingly, when the number of sequences for comparison increases, the number of comparisons to compute grows in a quadratic order. A current challenge of bioinformatic research, especially when taking into account the increasing number of sequenced organisms available, is to make this ever-growing number of comparisons computationally feasible in a reasonable amount of time.

MDAT- Aligning multiple domain arrangements.

Background: Proteins are composed of domains, protein segments that fold independently from the rest of the protein and have a specific function. During evolution the arrangement of domains can change: domains are gained, lost or their order is rearranged. To facilitate the analysis of these changes we propose the use of multiple domain alignments.

Transposable element islands facilitate adaptation to novel environments in an invasive species.

Adaptation requires genetic variation, but founder populations are generally genetically depleted. Here we sequence two populations of an inbred ant that diverge in phenotype to determine how variability is generated. Cardiocondyla obscurior has the smallest of the sequenced ant genomes and its structure suggests a fundamental role of transposable elements (TEs) in adaptive evolution.

Alignathon: a competitive assessment of whole-genome alignment methods.

Multiple sequence alignments (MSAs) are a prerequisite for a wide variety of evolutionary analyses. Published assessments and benchmark data sets for protein and, to a lesser extent, global nucleotide MSAs are available, but less effort has been made to establish benchmarks in the more general problem of whole-genome alignment (WGA). Using the same model as the successful Assemblathon competitions, we organized a competitive evaluation in which teams submitted their alignments and then assessments were performed collectively after all the submissions were received.

SARA-Coffee web server, a tool for the computation of RNA sequence and structure multiple alignments.

This article introduces the SARA-Coffee web server; a service allowing the online computation of 3D structure based multiple RNA sequence alignments. The server makes it possible to combine sequences with and without known 3D structures. Given a set of sequences SARA-Coffee outputs a multiple sequence alignment along with a reliability index for every sequence, column and aligned residue.

Using tertiary structure for the computation of highly accurate multiple RNA alignments with the SARA-Coffee package.

Motivation: Aligning RNAs is useful to search for homologous genes, study evolutionary relationships, detect conserved regions and identify any patterns that may be of biological relevance. Poor levels of conservation among homologs, however, make it difficult to compare RNA sequences, even when considering closely evolutionary related sequences.

Results: We describe SARA-Coffee, a tertiary structure-based multiple RNA aligner, which has been validated using BRAliDARTS, a new benchmark framework designed for evaluating tertiary structure-based multiple RNA aligners.

Epistasis as the primary factor in molecular evolution.

The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection, but it is unclear to what degree long-term protein evolution is constrained by epistasis, that is, instances when substitutions that are accepted in one genotype are deleterious in another. Here we obtain a quantitative estimate of the prevalence of epistasis in long-term protein evolution by relating data on amino-acid usage in 14 organelle proteins and 2 nuclear-encoded proteins to their rates of short-term evolution.

STRIKE: evaluation of protein MSAs using a single 3D structure.

Motivation: Evaluating alternative multiple protein sequence alignments is an important unsolved problem in Biology. The most accurate way of doing this is to use structural information. Unfortunately, most methods require at least two structures to be embedded in the alignment, a condition rarely met when dealing with standard datasets.

Using the T-Coffee package to build multiple sequence alignments of protein, RNA, DNA sequences and 3D structures.

T-Coffee (Tree-based consistency objective function for alignment evaluation) is a versatile multiple sequence alignment (MSA) method suitable for aligning most types of biological sequences. The main strength of T-Coffee is its ability to combine third party aligners and to integrate structural (or homology) information when building MSAs. The series of protocols presented here show how the package can be used to multiply align proteins, RNA and DNA sequences.

Upcoming challenges for multiple sequence alignment methods in the high-throughput era.

This review focuses on recent trends in multiple sequence alignment tools. It describes the latest algorithmic improvements including the extension of consistency-based methods to the problem of template-based multiple sequence alignments. Some results are presented suggesting that template-based methods are significantly more accurate than simpler alternative methods.