We present two algorithms in this paper: GeneWise, which predicts gene structure using similar protein sequences, and Genomewise, which provides a gene structure final parse across cDNA- and EST-defined spliced structure. Both algorithms are heavily used by the Ensembl annotation system. The GeneWise algorithm was developed from a principled combination of hidden Markov models (HMMs). Both algorithms are highly accurate and can provide both accurate and complete gene structures when used with the correct evidence.

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GeneWise and Genomewise

Ke yW ords 5-methylcytosine, DNA methyltransferase, transposons, genomic imprinting ■ Abstract Large-genome eukaryotes use heritable cytosine methylation to silence promoters, especially those associated with transposons and imprinted genes. Cytosine methylation does not reinforce or replace ancestral gene regulation pathways but instead endows methylated genomes with the ability to repress specific promoters in a manner that is buffered against changes in the internal and external environment. Recent studies have shown that the targeting of de novo methylation depends on multiple inputs; these include the interaction of repeated sequences, local states of histone lysine methylation, small RNAs and components of the RNAi pathway, and divergent and catalytically inert cytosine methyltransferase homologues that have acquired regulatory roles. There are multiple families of DNA (cytosine-5) methyltransferases in eukaryotes, and each family appears to be controlled by different regulatory inputs. Sequence-specific DNA- binding proteins, which regulate most aspects of gene expression, do not appear to be involved in the establishment or maintenance of genomic methylation patterns.

Eukaryotic cytosine methyltransferases.

Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates. A total of approximately 24,200 novel genes were identified, the translation products of which were classified together with Saccharomyces cerevisiae proteins into about 4,700 families, forming the basis for interspecific comparisons. Analysis of chromosome maps and genome redundancies reveal that the different yeast lineages have evolved through a marked interplay between several distinct molecular mechanisms, including tandem gene repeat formation, segmental duplication, a massive genome duplication and extensive gene loss.

Genome evolution in yeasts

Evidence suggests that haematopoietic stem cells might have unexpected developmental plasticity, highlighting therapeutic potential. For example, bone-marrow-derived hepatocytes can repopulate the liver of mice with fumarylacetoacetate hydrolase deficiency and correct their liver disease. To determine the underlying mechanism in this murine model, we performed serial transplantation of bone-marrow-derived hepatocytes. Here we show by Southern blot analysis that the repopulating hepatocytes in the liver were heterozygous for alleles unique to the donor marrow, in contrast to the original homozygous donor cells. Furthermore, cytogenetic analysis of hepatocytes transplanted from female donor mice into male recipients demonstrated 80,XXXY (diploid to diploid fusion) and 120,XXXXYY (diploid to tetraploid fusion) karyotypes, indicative of fusion between donor and host cells. We conclude that hepatocytes derived form bone marrow arise from cell fusion and not by differentiation of haematopoietic stem cells.

Cell fusion is the principal source of bone-marrow-derived hepatocytes

Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation.

/pdf/the-genome-sequence-of-the-rice-blast-fungus-magnaporthe-43sq8fkhmf.pdf

The genome sequence of the rice blast fungus Magnaporthe grisea

Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we
report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000
protein-coding genes—more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer
than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology
including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism,
and important differences in Ca21 signalling as compared with plants and animals. Neurospora possesses the widest array of
genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced
point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the
creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related
genes.

/pdf/the-genome-sequence-of-the-filamentous-fungus-neurospora-2jw3s2832k.pdf

David D. Perkins

Papers

The genome sequence of the filamentous fungus Neurospora crassa