Amino acid substitution during functionally constrained divergent evolution of protein sequences

In aligning homologous protein sequences, it is generally assumed that amino acid substitutions subsequent in time occur independently of amino acid substitutions previous in time, i.e. that patterns of mulation are similar at low and high sequence divergence. This assumption is examined here and shown to be incorrect in an interesting way. Separate mutation matrices were constructed for aligned protein sequence pairs at divergences ranging from 5 to 100 PAM units (point accepted mutations per 100 aligned positions). From these, the corresponding log-odds (Day-hoff) matrices, normalized to 250 PAM units, were constructed. The matrices show that the genetic code influences accepted point mutations strongly at early stages of divergence, while the chemical properties of the side chains dominate at more advanced stage

New distributional records for the Crowned Eagle (<i>Harpyhaliaetus coronatus</i>) in Western Argentina

The Crowned Eagle, <i>Harpyhaliaetus coronatus</i>, is regarded as endangered because of its low population numbers, the destruction of potential habitat, and the scarcity of records. Ecological studies on this species are required to develop conservation plans. We present 15 new distributional records obtained in the last 11 years. Based on the frequency of observed individuals and groups, and on the continuity of the habitats where it was recorded, we propose a priority area for ecological research on this species

New distributional records for the Crowned Eagle (<i>Harpyhaliaetus coronatus</i>) in Western Argentina

The Crowned Eagle, <i>Harpyhaliaetus coronatus</i>, is regarded as endangered because of its low population numbers, the destruction of potential habitat, and the scarcity of records. Ecological studies on this species are required to develop conservation plans. We present 15 new distributional records obtained in the last 11 years. Based on the frequency of observed individuals and groups, and on the continuity of the habitats where it was recorded, we propose a priority area for ecological research on this species

A methodology for determining amino-acid substitution matrices from set covers

We introduce a new methodology for the determination of amino-acid substitution matrices for use in the alignment of proteins. The new methodology is based on a pre-existing set cover on the set of residues and on the undirected graph that describes residue exchangeability given the set cover. For fixed functional forms indicating how to obtain edge weights from the set cover and, after that, substitution-matrix elements from weighted distances on the graph, the resulting substitution matrix can be checked for performance against some known set of reference alignments and for given gap costs. Finding the appropriate functional forms and gap costs can then be formulated as an optimization problem that seeks to maximize the performance of the substitution matrix on the reference alignment set. We give computational results on the BAliBASE suite using a genetic algorithm for optimization. Our results indicate that it is possible to obtain substitution matrices whose performance is either comparable to or surpasses that of several others, depending on the particular scenario under consideration

Pairwise alignment incorporating dipeptide covariation

Motivation: Standard algorithms for pairwise protein sequence alignment make the simplifying assumption that amino acid substitutions at neighboring sites are uncorrelated. This assumption allows implementation of fast algorithms for pairwise sequence alignment, but it ignores information that could conceivably increase the power of remote homolog detection. We examine the validity of this assumption by constructing extended substitution matrixes that encapsulate the observed correlations between neighboring sites, by developing an efficient and rigorous algorithm for pairwise protein sequence alignment that incorporates these local substitution correlations, and by assessing the ability of this algorithm to detect remote homologies. Results: Our analysis indicates that local correlations between substitutions are not strong on the average. Furthermore, incorporating local substitution correlations into pairwise alignment did not lead to a statistically significant improvement in remote homology detection. Therefore, the standard assumption that individual residues within protein sequences evolve independently of neighboring positions appears to be an efficient and appropriate approximation

Shaping Biological Knowledge: Applications in Proteomics

The central dogma of molecular biology has provided a meaningful principle for data integration in the field of genomics. In this context, integration reflects the known transitions from a chromosome to a protein sequence: transcription, intron splicing, exon assembly and translation. There is no such clear principle for integrating proteomics data, since the laws governing protein folding and interactivity are not quite understood. In our effort to bring together independent pieces of information relative to proteins in a biologically meaningful way, we assess the bias of bioinformatics resources and consequent approximations in the framework of small-scale studies. We analyse proteomics data while following both a data-driven (focus on proteins smaller than 10 kDa) and a hypothesis-driven (focus on whole bacterial proteomes) approach. These applications are potentially the source of specialized complements to classical biological ontologies