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Gene relics in the genome of the yeast Saccharomyces cerevisiae.

There is increasing evidence that DNA duplication is a common and ongoing process that plays a major role in molecular evolution of genomes and that a large fraction of the duplicated gene copies becomes non-functional by accumulation of deleterious mutations. In order to describe this phenomenon, we systematically searched the 6404 intergenic regions (IRs) of the genome of Saccharomyces cerevisiae for traces of coding sequences presenting degenerated but still recognizable sequence similarity with active open reading frames (5823 annotated ORFs). We detected a total of 124 anciently coding regions, or "gene relics", showing similarity to a total of 149 distinct active ORFs. This set of relics shows a continuum of sequence degeneration from those whose sequence is slightly altered compared to the functional ORF (classically defined as pseudogenes), to those that contains so many deleterious mutations, as to reach the limit of recognition. Gene relics are more concentrated in the subtelomeric regions of the chromosomes, reflecting the high plasticity of these regions. The presence of relics also revealed ancestral duplication events of chromosomal segments that were previously undetected. Some of these segments are intermingled with the more easily recognizable ancestral blocks of duplication, indicating successive duplication events. We present a compilation of all the data available, leading to a total of 278 pseudogenes in the genome of S. cerevisiae.

Chromosomes, Fungal↗

A bigger mouse? The rat genome unveiled.

Rattus norvegicus is an important experimental organism and interesting to evolutionary biologists. The recently published draft rat genome sequence provides us with insights into both the rat's evolution and its physiology. We learn more about genome evolution and, in particular, the adaptive significance of gene family expansions and the evolution of rodent genomes, which appears to have decelerated since the divergence of mouse and rat. An important observation is that some regions of genomes, many in noncoding regions, show very high sequence conservation, while others show unexpectedly fast evolution. Both of these may be pointers to functional significance.

Animals↗

Origin and evolution of mitochondria: what have we learnt from red algae?

The purpose of this review is to present an account of our current understanding of the structure, organization and evolution of mitochondrial genomes, and to discuss the origin and evolution of mitochondria from the perspective recently provided by the extensive sequencing of various mitochondrial genomes. Mitochondrial-en-coded protein phylogenies are congruent with nuclear phylogenies and strongly support a monophyletic origin of mitochondria. The newly available data from red-algal mitochondrial genomes, in particular, show that the structural and functional diversity of mitochondrial genomes can be accounted for by paralogous evolution. We also discuss the influence of other constraints, such as uniparental inheritance, on the evolution of genome organization in mitochondria.

DNA, Circular↗

A cell that dies during wild-type C. elegans development can function as a neuron in a ced-3 mutant.

Mutations in the C. elegans gene ced-3 prevent almost all programmed cell deaths, so that in a ced-3 mutant there are many extra cells. We show that the pharyngeal neuron M4 is essential for feeding in wild-type worms, but in a ced-3 mutant, one of the extra cells, probably MSpaaaaap (the sister of M4), can sometimes take over M4's function. The function of MSpaaaaap, unlike that of M4, is variable and subnormal. One possible explanation is that its fate, being hidden by death and not subject to selection, has drifted randomly during evolution. We suggest that such cells may play roles in the evolution of cell lineage analogous to those played by pseudogenes in the evolution of genomes.

Animals↗

The isochore organization of the human genome and its evolutionary history--a review.

This review will first present some properties (including compositional pattern, correlations between isochores and chromosomal bands, and gene distribution) of the human genome, the most extensively studied among vertebrate genomes. It will then explain how these properties came about during the evolution of the vertebrates.

Biological Evolution↗

To BAC or not to BAC: marine ecogenomics.

Most microbes in the ocean are still resistant to our collective cultivation efforts. Environmental microbial genomics provides science with the means for accessing and assessing the genomes, diversity, evolution and population dynamics of uncultured microorganisms--the ocean's hidden majority.

Chromosomes, Artificial, Bacterial↗

Gene regulatory network analysis in sea urchin embryos.

It may safely be predicted that GRN analysis will become increasingly important. It will come to underlie the causal study of development, the major effort underway to understand the regulatory code built into animal genomes and also the evolution of these genomes. Partly by serendipity, sea urchin embryos turn out to be a superb experimental material for GRN analysis. Their natural properties have, in turn, influenced the predilections of those who work on them, and between them and us, so to speak, this is now a developmental system of which we are rapidly gaining an unusually complete understanding. The causal linkages that control development of the whole embryo will be revealed, leading all the way from the heritable genomic regulatory code to the events of embryology. The fundamental experimental operation is the perturbation analysis: Here is where causality permeates the exploration. We have in this chapter summarized in some detail the requirements for perturbation GRN analysis in sea urchin embryos. But that is not all, nor is it enough to enable the assembly of a GRN: What is required is the combined application of elegant computational methods, of gene regulation molecular biology, of genomic sequence data, and of experimental embryology. As the results crystallize together, we can begin to see how far this powerful combination of methods and ideas is going to carry us.

Animals↗

Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits.

Molecular medicine began with Pauling's seminal work, which recognized sickle-cell anemia as a molecular disease, and with Ingram's demonstration of a specific chemical difference between the hemoglobins of normal and sickled human red blood cells. During the four decades that followed, investigations have focused on the gene--how mutations specifically alter DNA and how these changes affect the structure and expression of encoded proteins. Recently, however, the advances of the human genome project and the completion of total genome sequences for yeast and many bacterial species, have enabled investigators to view genetic information in the context of the entire genome. As a result, we recognize that the mechanisms for some genetic diseases are best understood at a genomic level. The evolution of the mammalian genome has resulted in the duplication of genes, gene segments and repeat gene clusters. This genome architecture provides substrates for homologous recombination between nonsyntenic regions of chromosomes. Such events can result in DNA rearrangements that cause disease.

Chromosome Aberrations↗

A type I and type II microsatellite linkage map of rainbow trout (Oncorhynchus mykiss) with presumptive coverage of all chromosome arms.

BACKGROUND: The development of large genomic resources has become a prerequisite to elucidate the wide-scale evolution of genomes and the molecular basis of complex traits. Linkage maps represent a first level of integration and utilization of such resources and the primary framework for molecular analyses of quantitative traits. Previously published linkage maps have already outlined the main peculiarities of the rainbow trout meiosis and a correspondance between linkage groups and chromosome arms has been recently established using fluorescent in situ hybridization. The number of chromosome arms which were covered by these maps remained unknown. RESULTS: We report an updated linkage map based on segregation analysis of more than nine hundred microsatellite markers in two doubled haploid gynogenetic lines. These markers segregated into 31 linkage groups spanning an approximate total map length of 2750 cM. Centromeres were mapped for all the linkage groups using meiogenetic lines. For each of the 31 linkage groups, the meta or acrocentric structure infered from centromere mapping was identical with those recently found with fluorescent in situ hybridization results. The present map is therefore assumed to cover the 52 chromosome arms which constitute the rainbow trout karyotype. Our data confirm the occurrence of a high interference level in this species. Homeologous regions were identified in eleven linkage groups, reflecting the tetraploid nature of the salmonid genome. The data supported the assumption that gene orders are conserved between duplicated groups and that each group is located on a single chromosome arm. Overall, a high congruence with already published rainbow trout linkage maps was found for both gene syntenies and orders. CONCLUSION: This new map is likely to cover the whole set of chromosome arms and should provide a useful framework to integrate existing or forthcoming rainbow trout linkage maps and other genomic resources. Since very large numbers of EST containing microsatellite sequences are available in databases, it becomes feasible to construct high-density linkage maps localizing known genes. This will facilitate comparative mapping and, eventually, identification of candidate genes in QTL studies.

Animals↗

Complexities of chromosome landing in a highly duplicated genome: toward map-based cloning of a gene controlling blackleg resistance in Brassica napus.

The LmR1 locus, which controls seedling resistance to the blackleg fungus Leptosphaeria maculans in the Brassica napus cultivar Shiralee, was positioned on linkage group N7. Fine genetic mapping in a population of 2500 backcross lines identified three molecular markers that cosegregated with LmR1. Additional linkage mapping in a second population colocalized a seedling resistance gene, ClmR1, from the cultivar Cresor to the same genetic interval on N7 as LmR1. Both genes were located in a region that showed extensive inter- and intragenomic duplications as well as intrachromosomal tandem duplications. The tandem duplications seem to have occurred in the Brassica lineage before the divergence of B. rapa and B. oleracea but after the separation of Brassica and Arabidopsis from a common ancestor. Microsynteny was found between the region on N7 carrying the resistance gene and the end of Arabidopsis chromosome 1, interrupted by a single inversion close to the resistance locus. The collinear region in Arabidopsis was assayed for the presence of possible candidate genes for blackleg resistance. These data provided novel insights into the genomic structure and evolution of plant resistance loci and an evaluation of the candidate gene approach using comparative mapping with a model organism.

Ascomycota↗

Artificial chromosomes: a blueprint for the future?

Recent developments in molecular genetics have led to the synthesis of an artificial human chromosome. Because the chromosome replicates and divides normally in human cells, this has exciting possibilities in terms of mankind's ability to influence evolutionary processes and to modify the human genome.

Centromere↗

The complete chloroplast genome of Secale strictum ssp. strictum provides insights into Triticeae evolution and breeding.

The complete chloroplast genome of Secale strictum ssp. strictum (Poaceae: Triticeae) was sequenced and analyzed to support its use in rye and wheat breeding. The genome is 137,063 bp long and includes a pair of inverted repeats (IRs; 21,580 bp each) that separate the small (SSC; 12,817 bp) and large (LSC; 81,086 bp) single-copy regions. It contains 113 genes: 74 protein-coding, 30 tRNA, four rRNA genes, and five conserved open reading frames. A total of 42 repeat sequences were identified, mainly in the LSC region, with direct repeats being most common. All mononucleotide SSRs consisted of A/T motifs. Seven highly variable regions were identified, offering potential as molecular markers for species identification and phylogenetic studies. Phylogenetic analysis based on 73 protein-coding genes confirmed the systematic placement of the species and showed that S. strictum ssp. strictum is closely related to S. cereale and other S. strictum accessions. This study presents the first complete plastome of S. strictum ssp. strictum, now available as a reference genome under GenBank accession number OL979486.

Genome, Chloroplast↗

Identification, characterization and comparative genomics of chimpanzee endogenous retroviruses.

BACKGROUND: Retrotransposons, the most abundant and widespread class of eukaryotic transposable elements, are believed to play a significant role in mutation and disease and to have contributed significantly to the evolution of genome structure and function. The recent sequencing of the chimpanzee genome is providing an unprecedented opportunity to study the functional significance of these elements in two closely related primate species and to better evaluate their role in primate evolution. RESULTS: We report here that the chimpanzee genome contains at least 42 separate families of endogenous retroviruses, nine of which were not previously identified. All but two (CERV 1/PTERV1 and CERV 2) of the 42 families of chimpanzee endogenous retroviruses were found to have orthologs in humans. Molecular analysis (PCR and Southern hybridization) of CERV 2 elements demonstrates that this family is present in chimpanzee, bonobo, gorilla and old-world monkeys but absent in human, orangutan and new-world monkeys. A survey of endogenous retroviral positional variation between chimpanzees and humans determined that approximately 7% of all chimpanzee-human INDEL variation is associated with endogenous retroviral sequences. CONCLUSION: Nine families of chimpanzee endogenous retroviruses have been transpositionally active since chimpanzees and humans diverged from a common ancestor. Seven of these transpositionally active families have orthologs in humans, one of which has also been transpositionally active in humans since the human-chimpanzee divergence about six million years ago. Comparative analyses of orthologous regions of the human and chimpanzee genomes have revealed that a significant portion of INDEL variation between chimpanzees and humans is attributable to endogenous retroviruses and may be of evolutionary significance.

Animals↗

The evolution, distribution and diversity of endogenous retroviruses.

The retroviral capacity for integration into the host genome can give rise to endogenous retroviruses (ERVs): retroviral sequences that are transmitted vertically as part of the host germ line, within which they may continue to replicate and evolve. ERVs represent both a unique archive of ancient viral sequence information and a dynamic component of host genomes. As such they hold great potential as informative markers for studies of both virus evolution and host genome evolution. Numerous novel ERVs have been described in recent years, particularly as genome sequencing projects have advanced. This review discusses the evolution of ERV lineages, considering the processes by which ERV distribution and diversity is generated. The diversity of ERVs isolated so far is summarised in terms of both their distribution across host taxa, and their relationships to recognised retroviral genera. Finally the relevance of ERVs to studies of genome evolution, host disease and viral ecology is considered, and recent findings discussed.

Animals↗

Nuclear-mitochondrial genomic profiling reveals a pattern of evolution in epithelial ovarian tumor stem cells.

Analyses of genome orthologs in cancer on the background of tumor heterogeneity, coupled with the recent identification that the tumor propagating capacity resides within a very small fraction of cells (the tumor stem cells-TSCs), has not been achieved. Here, we describe a strategy to explore genetic drift in the mitochondrial genome accompanying varying stem cell dynamics in epithelial ovarian cancer. A major and novel outcome is the identification of a specific mutant mitochondrial DNA profile associated with the TSC lineage that is drastically different from the germ line profile. This profile, however, is often camouflaged in the primary tumor, and sometimes may not be detected even after metastases, questioning the validity of whole tumor profiling towards determining individual prognosis. Continuing mutagenesis in subsets with a mutant mitochondrial genome could result in transformation through a cooperative effect with nuclear genes - a representative example in our study is a tumor suppressor gene viz. cAMP responsive element binding binding protein. This specific profile could be a critical predisposing step undertaken by a normal stem cell to overcome a tightly regulated mutation rate and DNA repair in its evolution towards tumorigenesis. Our findings suggest that varying stem cell dynamics and mutagenesis define TSC progression that may clinically translate into increasing tumor aggression with serious implications for prognosis.

Adenocarcinoma, Papillary↗

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↗

Naturally occurring mutations within HIV-1 V3 genomic RNA lead to antigenic variation dependent on a single amino acid substitution.

In a study on the evolution of genomic diversity of HIV-1, genomic RNA was isolated from serum of two individuals. Starting at the time of primary infection we collected six samples of serum from each patient over a period of 5 years. Ninety-four cDNA clones (50 of patient 1 and 44 of patient 495) of part of the envelope coding region including the principal neutralization domain (PND) were sequenced. Around the time of antibody seroconversion, genomic RNA levels reached a peak and the population of sequences was highly homogeneous. In the course of the infection, the number of amino acid substitutions accumulated, which led to a higher genomic diversity within successive samples and a drift in the consensus sequence, progressively differing from the first found consensus sequence. Fixation of a substitution at glycoprotein 120 amino acid 308 was observed in both patients between two time points (patient 1, H----P; patient 495, P----H). With the use of 16-meric synthetic peptides, differing only at the 308 position (H308 versus P308), antibody binding specificity was found to be dependent on this difference. In patient 495, the nonconservative (P308----H) substitution reduced the binding affinity with the patient's antibodies. Furthermore, antibody competition assays showed that the observed substitution at position 308 elicited a new antibody population, indicating antigenic variation. After the decline of V3-specific antibodies, the simultaneous increase in genomic RNA levels and progression to AIDS in patient 495, a new variant with major changes in the PND emerged, again forming a homogeneous population of sequences.

Acquired Immunodeficiency Syndrome↗