Structural and Evolutionary Genomics - Natural Selection in Genome Evolution

Paperback  458 pp  ISBN 0444521364      £52.00

• Summarizes the existing knowledge on genome organization and evolution in a self-contained book
• Discusses important open problem, without refraining from criticism whenever appropriate

Structural genomics is the study of the DNA of living organisms. Evolutionary genomics is the study of the history of the genome. These subjects are closely interlinked. They are approached in this book using as a guideline the investigations carried out in the author's laboratory, relevant literature is critically reviewed and some general conclusions are presented. The author and his collaborators have studied a vast number of genomes, ranging from prokaryotes to human, using different approaches, including physical chemistry of DNA, viral integration and molecular cytogenetics. As the subtitle indicates the book discusses the fundamental importance of natural selection in shaping genomes. In terms of numbers, neutral and nearly neutral mutations represent most mutations, but a "regional" control is exerted by natural selection (essentially negative or purifying selection). A "neo-selectionist" model is proposed for genome evolution.

Readership: Molecular and Cell Biologists, Geneticists from graduate student to Professor

Contents

Preface.

Part 1: Introduction.

• The genome: a short history of different views.
• Population genetics and molecular evolution.
• Three remarks on terminology.
• A brief chronology of our investigations.
• Molecular approaches to the study of the genome.

Part 2: Lessons from a small dispensable genome, the mitochondrial genome of yeast.

• The mitochondrial genome of yeast and the petite mutation.
• The "petite colonie" mutation.
• The petite mutation is accompanied by gross alterations of mitochondrial DNA.
• The AT spacers and the deletion hypothesis.
• The petite mutation is due to large deletions.
• The GC clusters.
• The excision sites.
• Genomes without genes.
• The origins of replication.
• Excision and recombination.
• The canonical and the surrogate origins of replication of petite genomes.
• The replication of petite genomes and the phenomenon of suppressivity.
• The ori sequences as transcription initiation sites.
• The elect of flanking sequences on the efficiency of replication of petite genomes.
• The ori- petites 14 and 26.
• Temperature and the replicative ability ofori- petites 14 and 26.
• The organization and evolution of the mitochondrial genome of yeast. 3
• The organization of the mitochondrial genome of yeast.
• The evolutionary origin of ori sequences.
• The evolutionary origin of the GC clusters.
• The evolutionary origin of the AT spacers and the var 1 gene.
• The non-coding sequences: evolutionary origin and biological role.

Part 3: The organisation of the vertebrate genome.

• Isochores and isochore families.
• The fractionation of the bovine genome
• The fractionation of eukaryotic main-band DNAs.
• Isochores and isochore families.
• Isochores and the draft human genome sequence.
• Other misunderstandings about isochores.
• Compositional patterns of coding sequences.
• Compositional correlations between coding and non-coding sequences.

Part 4: The compositional patterns of vertebrate genomes.

• The fish genomes.
• Compositional properties: a CsCl analysis.
• Compositional properties: a Cs₂SO₄/BAMD analysis.
• Compositional properties: an analysis of long sequences.
• Compositional properties of coding sequences and introns.
• Compositional correlations.
• Amphibian genomes.
• Reptilian genomes.
• Avian genomes.
• Mammalian genomes.

Part 5: Sequence distribution in the vertebrate genomes.

• Gene distribution in the vertebrate genome.
• The distribution of genes in the human genome: the two gene spaces.
• Properties of the two gene spaces.
• The distribution of genes in the vertebrate genomes.
• The distribution of CpG islands in the vertebrate genome.
• The distribution of CpG doublets and methylation in the vertebrate genome.
• CpG doublets.
• Two different CpG levels in vertebrate genomes.
• Two different methylation levels in vertebrate genomes.

Part 6: The distribution of integrated viral sequences, transposons and duplicated genes in the mammalian genome.

• The distribution of proviruses in the mammalian genome.
• The integration of retroviral sequences into the mammalian genome.
• The bimodal compositional distribution of retroviral genomes.
• The localization of integrated viral sequences in the host genome.
• An analysis of integration sites near host cell genes.
• The correlation between the isochore localization of integrated retroviral sequences and their transcription.
• Integration in "open" chromatin and/or near CpG islands.
• The causes of the compartmentalized, "isopycnic" localization of viral sequences. The distribution of repeated sequences in the mammalian genome.
• Alu and LINE repeats in human isochors.
• The evolutionary origin of repeat distribution: different viewpoints.
• Repeated sequences in coding sequences?
• The distribution of duplicated genes in the human genome.

Part 7: The organization of organization of chromosomes in vertebrates.

• Isochores and chromosomal bands.
• Compositional mapping.
• Compositional mapping based on physical maps.
• Chromosomal compositional mapping at a 400-band resolution.
• Chromosomal compositional mapping at a 850-band resolution.
• Genes, isochores and bands in human chromosomes 21 and 22.
• Replication timing, recombination and transcription of chromosomal bands.
• Replication timing of R and G bands.
• Recombination in chromosomes.
• Transcription of chromosomal bands.
• Isochores in the interphase nucleus.
• Distribution of the GC-richest and GC-poorest isochores in the interphase nucleus of human and chicken.
• Different compaction of the human GC-richest and GC-poorest chromosomal regions in interphase nuclei.
• The spatial distribution of genes in interphase nuclei.

Part 8: The organization of plant genomes.

• The organization of the nuclear genome of plants.
• Two classes of genes in plants.
• Gene distribution in the genomes of plants.
• The gene space in the genomes of Gramineae.
• Misunderstandings about the gene space ofGramineae.
• The gene space of other plants.
• Distribution of genes in the genome of Arabidopsis.
• A comparison of the genomes of Arabidopsis and Gramineae.
• The bimodal gene distribution in the tobacco genome.
• Methylation patterns in the nuclear genomes of plants.

Part 9: The compositional patterns of the genomes of invertebrates, unicellular eukaryotes and prokaryotes.

• The genome of a Urochordate, Ciona intestinalis.
• The genome of Drosophila melanogaster.
• The genome of Caenorhabditis elegans.
• The nuclear genome of unicellular eukaryotes.
• Compositional heterogeneityin prokaryotic genomes.
• CsCl gradient ultracentrifugation and traditional fixed-length window analysis.
• Generalized fixed-length window approaches.
• Intrinsic segmentation methods.
• Does intragenomic heterogeneity inE. coli arise from exogenous or endogenous DNA?
• Inter- and intra-genomic GC distributions.

Part 10: Gene composition and protein structure.

• The universal correlations.
• The universal correlations and the hydrophobicity of proteins.
• The universal correlation and imaginary genes.
• Compositional gene landscapes.
• Large-scale-features of the human gene landscape.
• Gene landscapes correspond to protein landscapes.
• Gene landscapes correspond to experimentally determined DNA landscapes.
• Nucleotide substitutions and composition in coding sequences. Correlations with protein structure.
• Synonymous and nonsynonymous substitution rates in mammalian genes are correlated with each other.
• Synonymous and nonsynonymous substitution rates are correlated with protein structure.
• Synonymous and nonsynonymous substitution rates are correlated with protein structure: an intragenic analysis of the Leishmania GP63 genes.
• Base compositions at nonsynonymous positions are correlated with protein structure and with the genetic code.
• Base composition at synonymous positions are correlated with protein structure.

Part 11: The compositional evolution of vertebrate genomes.

• Two modes of evolution in vertebrates.
• The maintenance of compositional patterns.
• The maintenance of the compositional patterns of warm-blooded vertebrates.
• The conservative mode of evolution and codon usage.
• Mutational biases in the human genome.
• The two major compositional shifts in vertebrate genomes.
• The major shifts.
• Compositional constraints and codon usage.
• Other changes accompanying the major shifts.
• The minor shift of murids.
• Differences in the compositional patterns of murids and other mammals.
• Isochore conservation in the MHC loci of human and mouse.
• The increased mutational input in murids.
• The whole-genome shifts of vertebrates.

Part 12: Natural selection and genetic drift in genome evolution: The neo-selectionist model.

• Molecular evolution theories and vertebrate genomics.
• Molecular evolution theories.
• Structural genomics of vertebrates.
• Our previous conclusions.
• Natural selection in the maintenance of compositional patterns of vertebrate genomes: the neo-selectionist model.
• Natural selection in the major shifts.
• The causes of the major shifts.
• Compositional changes and natural selection.
• The thermodynamic stability hypothesis: DNA results.
• The thermodynamic stability hypothesis: RNA results.
• The thermodynamic stability hypothesis: Protein results.
• The primum movens problem.
• Objections to selection.
• Alternative explanations for the major shifts.
• Natural selection and the "whole genome" shifts of prokaryotes and eukaryotes.

  Recapitulation.

• Structural genomics of warm-blooded vertebrates.
• Chromosomes and interphase nuclei.
• Comparative and evolutionary genomics of vertebrates.
• The eukaryotic genome.
• The prokaryotic genome.

Conclusions.
Abbreviations.
References.