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Martin J Lercher

Publications and source records attributed to Martin J Lercher.

At least 19 recordsLinked to original sources
PubMed2007

Prediction of effective genome size in metagenomic samples.

We introduce a novel computational approach to predict effective genome size (EGS; a measure that includes multiple plasmid copies, inserted sequences, and associated phages and viruses) from short sequencing reads of environmental genomics (or metagenomics) projects. We observe considerable EGS differences between environments and link this with ecologic complexity as well as species composition (for instance, the presence of eukaryotes). For example, we estimate EGS in a complex, organism-dense farm soil sample at about 6.3 megabases (Mb) whereas that of the bacteria therein is only 4.7 Mb; for bacteria in a nutrient-poor, organism-sparse ocean surface water sample, EGS is as low as 1.6 Mb. The method also permits evaluation of completion status and assembly bias in single-genome sequencing projects.

Artifacts↗
PubMed2006

Phylogenomic analysis reveals bees and wasps (Hymenoptera) at the base of the radiation of Holometabolous insects.

Comparative studies require knowledge of the evolutionary relationships between taxa. However, neither morphological nor paleontological data have been able to unequivocally resolve the major groups of holometabolous insects so far. Here, we utilize emerging genome projects to assemble and analyze a data set of 185 nuclear genes, resulting in a fully resolved phylogeny of the major insect model species. Contrary to the most widely accepted phylogenetic hypothesis, bees and wasps (Hymenoptera) are basal to the other major holometabolous orders, beetles (Coleoptera), moths (Lepidoptera), and flies (Diptera). We validate our results by meticulous examination of potential confounding factors. Phylogenomic approaches are thus able to resolve long-standing questions about the phylogeny of insects.

Animals↗
PubMed2006

Co-expressed yeast genes cluster over a long range but are not regularly spaced.

Analysis in yeast of the relationship between a gene's genomic position and its expression profile, derived from chip array data, suggests that both closely linked genes and genes spaced at regular intervals show correlated expression profiles. Unfortunately, yeast arrays are often printed in genomic order. The above results may hence reflect little more than known spatial biases within arrays. To circumvent this problem, we analyse spatially unbiased expression data derived from a large Northern blot study. We find that local domains of co-expressed genes range up to 30 genes (100 kb), and are thus much larger than previously considered. There is, by contrast, no evidence for periodicity of co-expression in yeast. We likewise find no convincing evidence for periodicity in the human or mouse genome. Further, analysis of yeast transcription factor binding data sets suggests that there is currently no statistical evidence for chromosomal periodicity of co-regulation.

Animals↗
PubMed2006

Chance and necessity in the evolution of minimal metabolic networks.

It is possible to infer aspects of an organism's lifestyle from its gene content. Can the reverse also be done? Here we consider this issue by modelling evolution of the reduced genomes of endosymbiotic bacteria. The diversity of gene content in these bacteria may reflect both variation in selective forces and contingency-dependent loss of alternative pathways. Using an in silico representation of the metabolic network of Escherichia coli, we examine the role of contingency by repeatedly simulating the successive loss of genes while controlling for the environment. The minimal networks that result are variable in both gene content and number. Partially different metabolisms can thus evolve owing to contingency alone. The simulation outcomes do preserve a core metabolism, however, which is over-represented in strict intracellular bacteria. Moreover, differences between minimal networks based on lifestyle are predictable: by simulating their respective environmental conditions, we can model evolution of the gene content in Buchnera aphidicola and Wigglesworthia glossinidia with over 80% accuracy. We conclude that, at least for the particular cases considered here, gene content of an organism can be predicted with knowledge of its distant ancestors and its current lifestyle.

Biological Evolution↗
PubMed2006

X-chromosome-wide profiling of MSL-1 distribution and dosage compensation in Drosophila.

In Drosophila, dosage compensation is achieved by a twofold up-regulation of the male X-linked genes and requires the association of the male-specific lethal complex (MSL) on the X chromosome. How the MSL complex is targeted to X-linked genes and whether its recruitment at a local level is necessary and sufficient to ensure dosage compensation remain poorly understood. Here we report the MSL-1-binding profile along the male X chromosome in embryos and male salivary glands isolated from third instar larvae using chromatin immunoprecipitation (ChIP) coupled with DNA microarray (ChIP-chip). This analysis has revealed that majority of the MSL-1 targets are primarily expressed during early embryogenesis and many target genes possess DNA replication element factor (DREF)-binding sites in their promoters. In addition, we show that MSL-1 distribution remains stable across development and that binding of MSL-1 on X-chromosomal genes does not correlate with transcription in male salivary glands. These results show that transcription per se on the X chromosome cannot be the sole signal for MSL-1 recruitment. Furthermore, genome-wide analysis of the dosage-compensated status of X-linked genes in male and female shows that most of the X chromosome remains compensated without direct MSL-1 binding near the gene. Our results, therefore, provide a comprehensive overview of MSL-1 binding and dosage-compensated status of X-linked genes and suggest a more global effect of MSL complex on X-chromosome regulation.

Animals↗
PubMed2006

Similar gene expression profiles do not imply similar tissue functions.

Although similarities in gene expression among tissues are commonly inferred to reflect functional constraints, this has never been formally tested. Furthermore, it is unclear which evolutionary processes are responsible for the observed similarities. When examining genome-wide expression data in mouse, we found that patterns of expression similarity between tissues extend to genes that are unlikely to function in the tissues. Thus, ectopic expression can seem coordinated across tissues. This indicates that knowledge of gene expression patterns per se is insufficient to infer gene function. Ectopic expression is possibly explained as expression leakage, caused by spreading of chromatin modifications or the transcription apparatus into neighboring genes.

Animals↗
PubMed2006

Genome-wide acceleration of protein evolution in flies (Diptera).

BACKGROUND: The rate of molecular evolution varies widely between proteins, both within and among lineages. To what extent is this variation influenced by genome-wide, lineage-specific effects? To answer this question, we assess the rate variation between insect lineages for a large number of orthologous genes. RESULTS: When compared to the beetle Tribolium castaneum, we find that the stem lineage of flies and mosquitoes (Diptera) has experienced on average a 3-fold increase in the rate of evolution. Pairwise gene comparisons between Drosophila and Tribolium show a high correlation between evolutionary rates of orthologous proteins. CONCLUSION: Gene specific divergence rates remain roughly constant over long evolutionary times, modulated by genome-wide, lineage-specific effects. Among the insects analysed so far, it appears that the Tribolium genes show the lowest rates of divergence. This has the practical consequence that homology searches for human genes yield significantly better matches in Tribolium than in Drosophila. We therefore suggest that Tribolium is better suited for comparisons between phyla than the widely employed dipterans.

Animals↗
PubMed2006

An integrated view of protein evolution.

Why do proteins evolve at different rates? Advances in systems biology and genomics have facilitated a move from studying individual proteins to characterizing global cellular factors. Systematic surveys indicate that protein evolution is not determined exclusively by selection on protein structure and function, but is also affected by the genomic position of the encoding genes, their expression patterns, their position in biological networks and possibly their robustness to mistranslation. Recent work has allowed insights into the relative importance of these factors. We discuss the status of a much-needed coherent view that integrates studies on protein evolution with biochemistry and functional and structural genomics.

Animals↗
PubMed2005

Adaptive evolution of bacterial metabolic networks by horizontal gene transfer.

Numerous studies have considered the emergence of metabolic pathways, but the modes of recent evolution of metabolic networks are poorly understood. Here, we integrate comparative genomics with flux balance analysis to examine (i) the contribution of different genetic mechanisms to network growth in bacteria, (ii) the selective forces driving network evolution and (iii) the integration of new nodes into the network. Most changes to the metabolic network of Escherichia coli in the past 100 million years are due to horizontal gene transfer, with little contribution from gene duplicates. Networks grow by acquiring genes involved in the transport and catalysis of external nutrients, driven by adaptations to changing environments. Accordingly, horizontally transferred genes are integrated at the periphery of the network, whereas central parts remain evolutionarily stable. Genes encoding physiologically coupled reactions are often transferred together, frequently in operons. Thus, bacterial metabolic networks evolve by direct uptake of peripheral reactions in response to changed environments.

Adaptation, Physiological↗
PubMed2005

Unusual linkage patterns of ligands and their cognate receptors indicate a novel reason for non-random gene order in the human genome.

BACKGROUND: Prior to the sequencing of the human genome it was typically assumed that, tandem duplication aside, gene order is for the most part random. Numerous observers, however, highlighted instances in which a ligand was linked to one of its cognate receptors, with some authors suggesting that this may be a general and/or functionally important pattern, possibly associated with recombination modification between epistatically interacting loci. Here we ask whether ligands are more closely linked to their receptors than expected by chance. RESULTS: We find no evidence that ligands are linked to their receptors more closely than expected by chance. However, in the human genome there are approximately twice as many co-occurrences of ligand and receptor on the same human chromosome as expected by chance. Although a weak effect, the latter might be consistent with a past history of block duplication. Successful duplication of some ligands, we hypothesise, is more likely if the cognate receptor is duplicated at the same time, so ensuring appropriate titres of the two products. CONCLUSION: While there is an excess of ligands and their receptors on the same human chromosome, this cannot be accounted for by classical models of non-random gene order, as the linkage of ligands/receptors is no closer than expected by chance. Alternative hypotheses for non-random gene order are hence worth considering.

Animals↗
PubMed2005

Horizontal gene transfer depends on gene content of the host.

Horizontal gene transfer is a major contributor to the evolution of bacterial genomes. We examine this process through a combination of comparative genomics and in silico analysis of the Escherichia coli metabolic network. We validate our horizontal transfer estimates by confirming the predicted gradual amelioration of GC content over time. We find that the chance of acquiring a gene by horizontal transfer is up to six times higher if an enzyme that catalyses a coupled metabolite flux is already encoded in the host genome.

Base Composition↗
PubMed2005

Evidence for widespread degradation of gene control regions in hominid genomes.

Although sequences containing regulatory elements located close to protein-coding genes are often only weakly conserved during evolution, comparisons of rodent genomes have implied that these sequences are subject to some selective constraints. Evolutionary conservation is particularly apparent upstream of coding sequences and in first introns, regions that are enriched for regulatory elements. By comparing the human and chimpanzee genomes, we show here that there is almost no evidence for conservation in these regions in hominids. Furthermore, we show that gene expression is diverging more rapidly in hominids than in murids per unit of neutral sequence divergence. By combining data on polymorphism levels in human noncoding DNA and the corresponding human-chimpanzee divergence, we show that the proportion of adaptive substitutions in these regions in hominids is very low. It therefore seems likely that the lack of conservation and increased rate of gene expression divergence are caused by a reduction in the effectiveness of natural selection against deleterious mutations because of the low effective population sizes of hominids. This has resulted in the accumulation of a large number of deleterious mutations in sequences containing gene control elements and hence a widespread degradation of the genome during the evolution of humans and chimpanzees.

Animals↗
PubMed2004

Gene expression, synteny, and local similarity in human noncoding mutation rates.

The human genome is organized with regard to many features such as isochores, Giemsa bands, clusters of genes with similar expression patterns, and contiguous regions with shared evolutionary histories (synteny blocks). In addition to these genomic features, it is clear that mutation rates also vary across the human genome. To address how mutation rates and genomic features are related, we analyzed substitution rates at three classes of putatively neutral noncoding sites (nongenic, intronic, and ancestral repeats) in approximately 14 Mb of human-chimpanzee alignments covering human chromosome 7. Patterns of mutation rate variation inferred from substitution rate variation differ among the three site classes. In particular, we find that intronic mutation rates are strongly affected by the breadth of expression of the genes in which they reside, with broadly expressed genes exhibiting low mutation rates, probably as a consequence of the transcription-coupled repair process acting in the germ line. All site classes show significant local similarities in mutation rate at the megabase scale, and regional similarities in nongenic mutation rate covary with blocks of synteny between the human and mouse genomes, indicating that the evolutionary history of a genomic region is an important determinant of mutation rate.

Animals↗
PubMed2004

Genomic regionality in rates of evolution is not explained by clustering of genes of comparable expression profile.

In mammalian genomes, linked genes show similar rates of evolution, both at fourfold degenerate synonymous sites (K4) and at nonsynonymous sites (KA). Although it has been suggested that the local similarity in the synonymous substitution rate is an artifact caused by the inclusion of disparately evolving gene pairs, we demonstrate here that this is not the case: after removal of disparately evolving genes, both (1) linked genes and (2) introns from the same gene have more similar silent substitution rates than expected by chance. What causes the local similarity in both synonymous and nonsynonymous substitution rates? One class of hypotheses argues that both may be related to the observed clustering of genes of comparable expression profile. We investigate these hypotheses using substitution rates from both human-mouse and mouse-rat comparisons, and employing three different methods to assay expression parameters. Although we confirm a negative correlation of expression breadth with both K4 and KA, we find no evidence that clustering of similarly expressed genes explains the clustering of genes of comparable substitution rates. If gene expression is not responsible, what about other causes? At least in the human-mouse comparison, the local similarity in KA can be explained by the covariation of KA and K4. As regards K4, our results appear consistent with the notion that local similarity is due to processes associated with meiotic recombination.

Animals↗
PubMed2003

A unification of mosaic structures in the human genome.

The human genome is a mosaic structure on many levels: there exist cytogenetic bands, GC composition bands (isochores) and clusters of broadly expressed genes. How might these inter-relate? It has been proposed that to optimize gene regulation, housekeeping genes should concentrate on transcriptionally competent chromosomal domains. Prior evidence suggests that regions of high GC and R bands are associated with such domains. Here we report that broadly expressed genes cluster in regions of high GC, and in R and lightest Giemsa bands. This is not only a confirmation of the adaptive hypothesis, but is also the first direct systematic evidence of a general interdependence of expression patterns with base composition and chromosome structure.

Azure Stains↗
PubMed2003

Evidence that the human X chromosome is enriched for male-specific but not female-specific genes.

There is increasing evidence that X chromosomes have an unusual complement of genes, especially genes that have sex-specific expression. However, whereas in worm and fly the X chromosome has a dearth of male-specific genes, in mice genes that are uniquely expressed in spermatogonia are especially abundant on the X chromosome. Is this latter enrichment true for nongermline, male-specific genes in mammals, and is it found also for female-specific genes? Here, using SAGE data, we show (1) that tissue-specific genes tend to be more abundant on the human X chromosome, (2) that, controlling for this effect, genes expressed exclusively in prostate are enriched on the human X chromosome, and (3) that genes expressed exclusively in mammary gland and ovary are not so enriched. This we propose is consistent with Rice's model of the evolution of sexually antagonistic alleles.

Animals↗