Detection of distant evolutionary relationships between protein families using theory of sequence profile-profile comparison

<p>Abstract</p> <p>Background</p> <p>Detection of common evolutionary origin (homology) is a primary means of inferring protein structure and function. At present, comparison of protein families represented as sequence profiles is arguably the most effective homology detection strategy. However, finding the best way to represent evolutionary information of a protein sequence family in the profile, to compare profiles and to estimate the biological significance of such comparisons, remains an active area of research.</p> <p>Results</p> <p>Here, we present a new homology detection method based on sequence profile-profile comparison. The method has a number of new features including position-dependent gap penalties and a global score system. Position-dependent gap penalties provide a more biologically relevant way to represent and align protein families as sequence profiles. The global score system enables an analytical solution of the statistical parameters needed to estimate the statistical significance of profile-profile similarities. The new method, together with other state-of-the-art profile-based methods (HHsearch, COMPASS and PSI-BLAST), is benchmarked in all-against-all comparison of a challenging set of SCOP domains that share at most 20% sequence identity. For benchmarking, we use a reference ("gold standard") free model-based evaluation framework. Evaluation results show that at the level of protein domains our method compares favorably to all other tested methods. We also provide examples of the new method outperforming structure-based similarity detection and alignment. The implementation of the new method both as a standalone software package and as a web server is available at <url>http://www.ibt.lt/bioinformatics/coma</url>.</p> <p>Conclusion</p> <p>Due to a number of developments, the new profile-profile comparison method shows an improved ability to match distantly related protein domains. Therefore, the method should be useful for annotation and homology modeling of uncharacterized proteins.</p

Identifying and Seeing beyond Multiple Sequence Alignment Errors Using Intra-Molecular Protein Covariation

BACKGROUND: There is currently no way to verify the quality of a multiple sequence alignment that is independent of the assumptions used to build it. Sequence alignments are typically evaluated by a number of established criteria: sequence conservation, the number of aligned residues, the frequency of gaps, and the probable correct gap placement. Covariation analysis is used to find putatively important residue pairs in a sequence alignment. Different alignments of the same protein family give different results demonstrating that covariation depends on the quality of the sequence alignment. We thus hypothesized that current criteria are insufficient to build alignments for use with covariation analyses. METHODOLOGY/PRINCIPAL FINDINGS: We show that current criteria are insufficient to build alignments for use with covariation analyses as systematic sequence alignment errors are present even in hand-curated structure-based alignment datasets like those from the Conserved Domain Database. We show that current non-parametric covariation statistics are sensitive to sequence misalignments and that this sensitivity can be used to identify systematic alignment errors. We demonstrate that removing alignment errors due to 1) improper structure alignment, 2) the presence of paralogous sequences, and 3) partial or otherwise erroneous sequences, improves contact prediction by covariation analysis. Finally we describe two non-parametric covariation statistics that are less sensitive to sequence alignment errors than those described previously in the literature. CONCLUSIONS/SIGNIFICANCE: Protein alignments with errors lead to false positive and false negative conclusions (incorrect assignment of covariation and conservation, respectively). Covariation analysis can provide a verification step, independent of traditional criteria, to identify systematic misalignments in protein alignments. Two non-parametric statistics are shown to be somewhat insensitive to misalignment errors, providing increased confidence in contact prediction when analyzing alignments with erroneous regions because of an emphasis on they emphasize pairwise covariation over group covariation

Cumulative culture in nonhumans : overlooked findings from Japanese monkeys?

The authors thank Corpus Christi College (Cambridge) for funding DS’s visit to Koshima and Prof. Tetsuro Matsuzawa for funding WCM’s visit to Koshima.Cumulative culture, generally known as the increasing complexity or efficiency of cultural behaviors additively transmitted over successive generations, has been emphasized as a hallmark of human evolution. Recently, reviews of candidates for cumulative culture in nonhuman species have claimed that only humans have cumulative culture. Here, we aim to scrutinize this claim, using current criteria for cumulative culture to re-evaluate overlooked qualitative but longitudinal data from a nonhuman primate, the Japanese monkey (Macaca fuscata). We review over 60 years of Japanese ethnography of Koshima monkeys, which indicate that food-washing behaviors (e.g., of sweet potato tubers and wheat grains) seem to have increased in complexity and efficiency over time. Our reassessment of the Koshima ethnography is preliminary and nonquantitative, but it raises the possibility that cumulative culture, at least in a simple form, occurs spontaneously and adaptively in other primates and nonhumans in nature.Publisher PDFPeer reviewe

The cannabinoid system and male reproductive functions.

Cannabinoids, the main active components of marijuana, have been shown to exert different adverse effects on male reproduction both in vertebrates and invertebrates. In vivo, cannabinoids exert negative effects on hypothalamic-hypophyseal reproductive hormone secretion and testicular endocrine and exocrine functions. Furthermore, a large amount of experimental data obtained in vitro have clearly shown that cannabinoids negatively influence important sperm functions, including motility and acrosome reaction, two fundamental processes necessary for oocyte fertilisation. These inhibitory effects are mediated by the direct action of cannabinoids on sperm through the activation of the cannabinoid receptor subtype CNR1 that has been shown to be expressed in mature sperm. In the present paper, we briefly review the effects of cannabinoids and endocannabinoids, a particular group of endogenously produced cannabinoids, on male reproductive function

Dermatologia e gestação Dermatology and pregnancy

Neste estudo conduz-se uma revisão bibliográfica da literatura sobre dermatologia e gravidez abrangendo o período de 1962 a 2003. O banco de dados do Medline foi consultado com referência ao mesmo período. Não se incluiu a colestase intra-hepática da gravidez por não ser ela uma dermatose primária; contudo deve ser feito o diagnóstico diferencial entre suas manifestações na pele e as dermatoses específicas da gravidez. Este apanhado engloba as características clínicas e o prognóstico das alterações fisiológicas da pele durante a gravidez, as dermatoses influenciadas pela gravidez e as dermatoses específicas da gravidez. Ao final apresenta-se uma discussão sobre drogas e gravidez.<br>This study is a literature review on dermatology and pregnancy from 1962 to 2003, based on Medline database search. Intrahepatic cholestasis of pregnancy was not included because it is not a primary dermatosis; however, its secondary skin lesions must be differentiated from specific dermatoses of pregnancy. This overview comprises clinical features and prognosis of the physiologic skin changes that occur during pregnancy; dermatoses influenced by pregnancy and the specific dermatoses of pregnancy. A discussion on drugs and pregnancy is presented at the end of this review