CiteULike: lp2's no-tag

The evolution of courtship behaviors through the origination of a new gene in Drosophila

2008-07-18T10:06:42-00:00

PNAS

A Probabilistic Model of Local Sequence Alignment That Simplifies Statistical Significance Estimation

S Eddy — 2008-06-02T08:22:15-00:00

PLoS Computational Biology, Vol. 5, No. 4. (May 2008)

MicroRNAs keeping cells in formation

Eric Miska — 2008-05-03T19:51:12-00:00

Nature Cell Biology, Vol. 10, No. 5., pp. 501-502.

How to succeed in science: a concise guide for young biomedical scientists. Part I: taking the plunge

Jonathan Yewdell — 2008-04-23T12:46:10-00:00

Nat Rev Mol Cell Biol, Vol. 9, No. 5. (May 2008), pp. 413-416.

Raising the estimate of functional human sequences.

Michael Pheasant — 2007-08-13T08:26:55-00:00

Genome Res (9 August 2007)

While less than 1.5% of the mammalian genome encodes proteins, it is now evident that the vast majority is transcribed, mainly into non-protein-coding RNAs. This raises the question of what fraction of the genome is functional, i.e., composed of sequences that yield functional products, are required for the expression (regulation or processing) of these products, or are required for chromosome replication and maintenance. Many of the observed noncoding transcripts are differentially expressed, and, while most have not yet been studied, increasing numbers are being shown to be functional and/or trafficked to specific subcellular locations, as well as exhibit subtle evidence of selection. On the other hand, analyses of conservation patterns indicate that only approximately 5% (3%-8%) of the human genome is under purifying selection for functions common to mammals. However, these estimates rely on the assumption that reference sequences (usually ancient transposon-derived sequences) have evolved neutrally, which may not be the case, and if so would lead to an underestimate of the fraction of the genome under evolutionary constraint. These analyses also do not detect functional sequences that are evolving rapidly and/or have acquired lineage-specific functions. Indeed, many regulatory sequences and known functional noncoding RNAs, including many microRNAs, are not conserved over significant evolutionary distances, and recent evidence from the ENCODE project suggests that many functional elements show no detectable level of sequence constraint. Thus, it is likely that much more than 5% of the genome encodes functional information, and although the upper bound is unknown, it may be considerably higher than currently thought.

Different cognitive processes underlie human mate choices and mate preferences -- Todd et al., 10.1073/pnas.0705290104 -- Proceedings of the National Academy of Sciences

2007-09-08T16:18:42-00:00

Natural history and evolutionary principles of gene duplication in fungi

Ilan Wapinski — 2007-09-05T18:18:33-00:00

Nature, Vol. 449, No. 7158., pp. 54-61.

Deletion of Ultraconserved Elements Yields Viable Mice

Nadav Ahituv — 2007-09-05T08:22:04-00:00

PLoS Biology, Vol. 5, No. 9. (1 September 2007), e234.

Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the necessities of these elements in vivo, we removed four noncoding ultraconserved elements (ranging in length from 222 to 731 base pairs) from the mouse genome. To maximize the likelihood of observing a phenotype, we chose to delete elements that function as enhancers in a mouse transgenic assay and that are near genes that exhibit marked phenotypes both when completely inactivated in the mouse and when their expression is altered due to other genomic modifications. Remarkably, all four resulting lines of mice lacking these ultraconserved elements were viable and fertile, and failed to reveal any critical abnormalities when assayed for a variety of phenotypes including growth, longevity, pathology, and metabolism. In addition, more targeted screens, informed by the abnormalities observed in mice in which genes in proximity to the investigated elements had been altered, also failed to reveal notable abnormalities. These results, while not inclusive of all the possible phenotypic impact of the deleted sequences, indicate that extreme sequence constraint does not necessarily reflect crucial functions required for viability.

The Diploid Genome Sequence of an Individual Human

Samuel Levy — 2007-09-04T11:15:47-00:00

PLoS Biology, Vol. 5, No. 10. (1 October 2007), e254.

Presented here is a genome sequence of an individual human. It was produced from ∼32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel) included 3,213,401 single nucleotide polymorphisms (SNPs), 53,823 block substitutions (2–206 bp), 292,102 heterozygous insertion/deletion events (indels)(1–571 bp), 559,473 homozygous indels (1–82,711 bp), 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information.

The Mirtron Pathway Generates microRNA-Class Regulatory RNAs in Drosophila.

Katsutomo Okamura — 2007-07-02T13:47:59-00:00

Cell (26 June 2007)

The canonical microRNA (miRNA) pathway converts primary hairpin precursor transcripts into approximately 22 nucleotide regulatory RNAs via consecutive cleavages by two RNase III enzymes, Drosha and Dicer. In this study, we characterize Drosophila small RNAs that derive from short intronic hairpins termed "mirtrons." Their nuclear biogenesis appears to bypass Drosha cleavage, which is essential for miRNA biogenesis. Instead, mirtron hairpins are defined by the action of the splicing machinery and lariat-debranching enzyme, which yield pre-miRNA-like hairpins. The mirtron pathway merges with the canonical miRNA pathway during hairpin export by Exportin-5, and both types of hairpins are subsequently processed by Dicer-1/loqs. This generates small RNAs that can repress perfectly matched and seed-matched targets, and we provide evidence that they function, at least in part, via the RNA-induced silencing complex effector Ago1. These findings reveal that mirtrons are an alternate source of miRNA-type regulatory RNAs.

Biological applications of the theory of birth-and-death processes

Artem Novozhilov — 2007-08-24T08:53:18-00:00

Brief Bioinform, Vol. 7, No. 1. (1 March 2006), pp. 70-85.

In this review, we discuss applications of the theory of birth-and-death processes to problems in biology, primarily, those of evolutionary genomics. The mathematical principles of the theory of these processes are briefly described. Birth-and-death processes, with some straightforward additions such as innovation, are a simple, natural and formal framework for modeling a vast variety of biological processes such as population dynamics, speciation, genome evolution, including growth of paralogous gene families and horizontal gene transfer and somatic evolution of cancers. We further describe how empirical data, e.g. distributions of paralogous gene family size, can be used to choose the model that best reflects the actual course of evolution among different versions of birth-death-and-innovation models. We conclude that birth-and-death processes, thanks to their mathematical transparency, flexibility and relevance to fundamental biological processes, are going to be an indispensable mathematical tool for the burgeoning field of systems biology. 10.1093/bib/bbk006

Contribution of Horizontal Gene Transfer to the Evolution of Saccharomyces cerevisiae

Charles Hall — 2007-03-16T15:00:29-00:00

Eukaryotic Cell, Vol. 4, No. 6. (1 June 2005), pp. 1102-1115.

The genomes of the hemiascomycetes Saccharomyces cerevisiae and Ashbya gossypii have been completely sequenced, allowing a comparative analysis of these two genomes, which reveals that a small number of genes appear to have entered these genomes as a result of horizontal gene transfer from bacterial sources. One potential case of horizontal gene transfer in A. gossypii and 10 potential cases in S. cerevisiae were identified, of which two were investigated further. One gene, encoding the enzyme dihydroorotate dehydrogenase (DHOD), is potentially a case of horizontal gene transfer, as shown by sequencing of this gene from additional bacterial and fungal species to generate sufficient data to construct a well-supported phylogeny. The DHOD-encoding gene found in S. cerevisiae, URA1 (YKL216W), appears to have entered the Saccharomycetaceae after the divergence of the S. cerevisiae lineage from the Candida albicans lineage and possibly since the divergence from the A. gossypii lineage. This gene appears to have come from the Lactobacillales, and following its acquisition the endogenous eukaryotic DHOD gene was lost. It was also shown that the bacterially derived horizontally transferred DHOD is required for anaerobic synthesis of uracil in S. cerevisiae. The other gene discussed in detail is BDS1, an aryl- and alkyl-sulfatase gene of bacterial origin that we have shown allows utilization of sulfate from several organic sources. Among the eukaryotes, this gene is found in S. cerevisiae and Saccharomyces bayanus and appears to derive from the alpha-proteobacteria. 10.1128/EC.4.6.1102-1115.2005

Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789

Wu Wei — 2007-08-02T15:14:27-00:00

PNAS, Vol. 104, No. 31. (31 July 2007), pp. 12825-12830.

We sequenced the genome of Saccharomyces cerevisiae strain YJM789, which was derived from a yeast isolated from the lung of an AIDS patient with pneumonia. The strain is used for studies of fungal infections and quantitative genetics because of its extensive phenotypic differences to the laboratory reference strain, including growth at high temperature and deadly virulence in mouse models. Here we show that the approx12-Mb genome of YJM789 contains approx60,000 SNPs and approx6,000 indels with respect to the reference S288c genome, leading to protein polymorphisms with a few known cases of phenotypic changes. Several ORFs are found to be unique to YJM789, some of which might have been acquired through horizontal transfer. Localized regions of high polymorphism density are scattered over the genome, in some cases spanning multiple ORFs and in others concentrated within single genes. The sequence of YJM789 contains clues to pathogenicity and spurs the development of more powerful approaches to dissecting the genetic basis of complex hereditary traits. 10.1073/pnas.0701291104

Biological network mapping and source signal deduction

Mark Brynildsen — 2007-08-09T12:59:41-00:00

Bioinformatics, Vol. 23, No. 14. (15 July 2007), pp. 1783-1791.

Motivation: Many biological networks, including transcriptional regulation, metabolism, and the absorbance spectra of metabolite mixtures, can be represented in a bipartite fashion. Key to understanding these bipartite networks are the network architecture and governing source signals. Such information is often implicitly imbedded in the data. Here we develop a technique, network component mapping (NCM), to deduce bipartite network connectivity and regulatory signals from data without any need for prior information. Results: We demonstrate the utility of our approach by analyzing UV-vis spectra from mixtures of metabolites and gene expression data from Saccharomyces cerevisiae. From UV-vis spectra, hidden mixing networks and pure component spectra (sources) were deduced to a higher degree of resolution with our method than other current bipartite techniques. Analysis of S.cerevisiae gene expression from two separate environmental conditions (zinc and DTT treatment) yielded transcription networks consistent with ChIP-chip derived network connectivity. Due to the high degree of noise in gene expression data, the transcription network for many genes could not be inferred. However, with relatively clean expression data, our technique was able to deduce hidden transcription networks and instances of combinatorial regulation. These results suggest that NCM can deduce correct network connectivity from relatively accurate data. For noisy data, NCM yields the sparsest network capable of explaining the data. In addition, partial knowledge of the network topology can be incorporated into NCM as constraints. Availability: Algorithm available on request from the authors. Soon to be posted on the web, http://www.seas.ucla.edu/~liaoj/ Contact: liaoj@ucla.edu Supplementary information: Supplementary data are available at Bioinformatics online. 10.1093/bioinformatics/btm246

Logistic regression protects against population structure in genetic association studies

Efrosini Setakis — 2006-08-03T22:55:07-00:00

Genome Res., Vol. 16, No. 2. (1 February 2006), pp. 290-296.

We conduct an extensive simulation study to compare the merits of several methods for using null (unlinked) markers to protect against false positives due to cryptic substructure in population-based genetic association studies. The more sophisticated "structured association" methods perform well but are computationally demanding and rely on estimating the correct number of subpopulations. The simple and fast "genomic control" approach can lose power in certain scenarios. We find that procedures based on logistic regression that are flexible, computationally fast, and easy to implement also provide good protection against the effects of cryptic substructure, even though they do not explicitly model the population structure. 10.1101/gr.4346306

A Markov Chain Monte Carlo Method for Estimating Population Mixing Using Y-chromosome Markers: Mixing of the Han People in China

Jow — 2007-04-17T10:19:58-00:00

Annals of Human Genetics, Vol. 71, No. 3. (May 2006), pp. 407-420.

A Markov Chain Monte Carlo Approach for Joint Inference of Population Structure and Inbreeding Rates From Multilocus Genotype Data

Hong Gao — 2007-07-20T12:22:36-00:00

Genetics, Vol. 176, No. 3. (1 July 2007), pp. 1635-1651.

Nonrandom mating induces correlations in allelic states within and among loci that can be exploited to understand the genetic structure of natural populations (WRIGHT 1965). For many species, it is of considerable interest to quantify the contribution of two forms of nonrandom mating to patterns of standing genetic variation: inbreeding (mating among relatives) and population substructure (limited dispersal of gametes). Here, we extend the popular Bayesian clustering approach STRUCTURE (PRITCHARD et al. 2000) for simultaneous inference of inbreeding or selfing rates and population-of-origin classification using multilocus genetic markers. This is accomplished by eliminating the assumption of HardyWeinberg equilibrium within clusters and, instead, calculating expected genotype frequencies on the basis of inbreeding or selfing rates. We demonstrate the need for such an extension by showing that selfing leads to spurious signals of population substructure using the standard STRUCTURE algorithm with a bias toward spurious signals of admixture. We gauge the performance of our method using extensive coalescent simulations and demonstrate that our approach can correct for this bias. We also apply our approach to understanding the population structure of the wild relative of domesticated rice, Oryza rufipogon, an important partially selfing grass species. Using a sample of n = 16 individuals sequenced at 111 random loci, we find strong evidence for existence of two subpopulations, which correlates well with geographic location of sampling, and estimate selfing rates for both groups that are consistent with estimates from experimental data (s approx 0.480.70). 10.1534/genetics.107.072371

A Computational Pipeline for High- Throughput Discovery of cis-Regulatory Noncoding RNA in Prokaryotes

Zizhen Yao — 2007-07-08T12:17:39-00:00

PLoS Computational Biology, Vol. 3, No. 7. (1 July 2007), e126.

Noncoding RNAs (ncRNAs) are important functional RNAs that do not code for proteins. We present a highly efficient computational pipeline for discovering cis-regulatory ncRNA motifs de novo. The pipeline differs from previous methods in that it is structure-oriented, does not require a multiple-sequence alignment as input, and is capable of detecting RNA motifs with low sequence conservation. We also integrate RNA motif prediction with RNA homolog search, which improves the quality of the RNA motifs significantly. Here, we report the results of applying this pipeline to Firmicute bacteria. Our top-ranking motifs include most known Firmicute elements found in the RNA family database (Rfam). Comparing our motif models with Rfam's hand-curated motif models, we achieve high accuracy in both membership prediction and base-pair–level secondary structure prediction (at least 75% average sensitivity and specificity on both tasks). Of the ncRNA candidates not in Rfam, we find compelling evidence that some of them are functional, and analyze several potential ribosomal protein leaders in depth.

Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789 -- Wei et al. 104 (31): 12825 -- Proceedings of the National Academy of Sciences

2007-08-02T09:23:12-00:00

Population Structure and Eigenanalysis

Nick Patterson — 2007-05-01T04:58:14-00:00

PLoS Genetics, Vol. 2, No. 12. (1 December 2006), e190.

Current methods for inferring population structure from genetic data do not provide formal significance tests for population differentiation. We discuss an approach to studying population structure (principal components analysis) that was first applied to genetic data by Cavalli-Sforza and colleagues. We place the method on a solid statistical footing, using results from modern statistics to develop formal significance tests. We also uncover a general “phase change” phenomenon about the ability to detect structure in genetic data, which emerges from the statistical theory we use, and has an important implication for the ability to discover structure in genetic data: for a fixed but large dataset size, divergence between two populations (as measured, for example, by a statistic like FST) below a threshold is essentially undetectable, but a little above threshold, detection will be easy. This means that we can predict the dataset size needed to detect structure.

Geography predicts neutral genetic diversity of human populations

Franck Prugnolle — 2007-07-20T09:56:59-00:00

Current Biology, Vol. 15, No. 5. (8 March 2005), pp. R159-R160.

A leading theory for the origin of modern humans, the `recent African origin' (RAO) model [], postulates that the ancestors of all modern humans originated in East Africa and that, around 100,000 years ago, some modern humans left the African continent and subsequently colonised the entire world, displacing previously established human species such as Neanderthals in Europe [ and ]. This scenario is supported by the observation that human populations from Africa are genetically the most diverse [] and that the genetic diversity of non-African populations is negatively correlated with their genetic differentiation towards populations from Africa [].

The effect of ancient population bottlenecks on human phenotypic variation

Andrea Manica — 2007-07-18T23:12:57-00:00

Nature, Vol. 448, No. 7151., pp. 346-348.

PLoS ONE: Indexing Strategies for Rapid Searches of Short Words in Genome Sequences

2007-07-20T09:16:36-00:00

New Taxonomy and the Origin of Species

Shai Meiri — 2007-07-18T13:32:38-00:00

PLoS Biology, Vol. 5, No. 7. (1 July 2007), e194.

Is urbanization scrambling the genetic structure of human populations? A case study

M Ashrafian-Bonab — 2006-11-15T15:50:17-00:00

Heredity, Vol. aop, No. current.

Decreased demands on cognitive control reveal the neural processing benefits of forgetting.

Brice A Kuhl — 2007-06-18T06:22:47-00:00

Nat Neurosci (3 June 2007)

Remembering often requires the selection of goal-relevant memories in the face of competition from irrelevant memories. Although there is a cost of selecting target memories over competing memories (increased forgetting of the competing memories), here we report neural evidence for the adaptive benefits of forgetting-namely, reduced demands on cognitive control during future acts of remembering. Functional magnetic resonance imaging during selective retrieval showed that repeated retrieval of target memories was accompanied by dynamic reductions in the engagement of functionally coupled cognitive control mechanisms that detect (anterior cingulate cortex) and resolve (dorsolateral and ventrolateral prefrontal cortex) mnemonic competition. Strikingly, regression analyses revealed that this prefrontal disengagement tracked the extent to which competing memories were forgotten; greater forgetting of competing memories was associated with a greater decline in demands on prefrontal cortex during target remembering. These findings indicate that, although forgetting can be frustrating, memory might be adaptive because forgetting confers neural processing benefits.

Studying Individual Events in Biology - Annual Review of Biochemistry, 76(1):419 - Full Text

2007-06-26T07:08:40-00:00

The Nonsense-Mediated Decay RNA Surveillance Pathway - Annual Review of Biochemistry, 76(1):51 - Full Text

2007-06-25T13:38:23-00:00

Structure and Mechanism of Helicases and Nucleic Acid Translocases - Annual Review of Biochemistry, 76(1):23 - Full Text

2007-06-25T13:13:01-00:00

Origin and Evolution of Human microRNAs From Transposable Elements -- Piriyapongsa et al. 176 (2): 1323 -- Genetics

2007-06-25T13:02:19-00:00

Why Do We Still Have a Maternally Inherited Mitochondrial DNA? Insights from Evolutionary Medicine - Annual Review of Biochemistry, 76(1):781 - Full Text

2007-06-25T12:54:56-00:00

Enhanced activity of the GmarMT1 promoter from the mycorrhizal fungus Gigaspora margarita at limited carbon supply.

Roberta Bergero — 2007-05-29T12:02:05-00:00

Fungal Genet Biol (30 January 2007)

Metallothioneins are low molecular weight polypeptides, present in most eukaryotic phyla, with role in metal homeostasis and detoxification. We previously reported the identification and the characterization of a metallothionein gene (GmarMT1) from the arbuscular mycorrhizal fungus Gigaspora margarita. Here, we have used real-time quantitative RT-PCR to show that GmarMT1 expression was turned off during the symbiotic fungal growth in the hexose-rich mycorrhizal apoplast, whereas transcripts were abundant during all other fungal growth stages, when products of lipid breakdown and the glyoxylate cycle feed carbohydrate-consuming pathways. In support of a nutritional regulation of GmarMT1 expression, we show that transcriptional activity of GmarMT1 promoter in yeast was strongly induced by glucose starvation (up to 20 times the basal level). We speculate that GmarMT1-encoded protein, with its proved metal binding ability, could regulate the homeostasis of zinc, a fundamental cofactor involved in C metabolism regulation and glucose repression.