A prominent role for segmental duplications in modeling Eukaryotic genomes

Segmental duplications (SDs) are a major element of eukaryotic genomes. Whereas their quantitative importance vary among lineages, SDs appear as a fundamental trait of the recent evolution of great-apes genomes. The chromosomal instability generated by these SDs has dramatic consequences both in generating a high level of polymorphisms among individuals and in originating numerous human pathogenic diseases. However, even though the importance of SDs has been increasingly recognized at the genomic level, some of the molecular pathways that lead to their formation remain obscure. Here we review recent evidences that the interplay between several mechanisms, some conservative, some based on replication, explains the complex SDs patterns observed in many genomes. Recent experimental studies have indeed partially unveiled some important aspects of these mechanisms, shedding interesting and unsuspected new lights on the dramatic plasticity of eukaryotic genomes. To cite this article: R. Koszul, G. Fischer, C. R. Biologies 332 (2009).     

Dissecting plant genomes with the PLAZA comparative genomics platform

With the arrival of low-cost, next-generation sequencing, a multitude of new plant genomes are being publicly released, providing unseen opportunities and challenges for comparative genomics studies. Here, we present PLAZA 2.5, a user-friendly online research environment to explore genomic information from different plants. This new release features updates to previous genome annotations and a substantial number of newly available plant genomes as well as various new interactive tools and visualizations. Currently, PLAZA hosts 25 organisms covering a broad taxonomic range, including 13 eudicots, five monocots, one lycopod, one moss, and five algae. The available data consist of structural and functional gene annotations, homologous gene families, multiple sequence alignments, phylogenetic trees, and colinear regions within and between species. A new Integrative Orthology Viewer, combining information from different orthology prediction methodologies, was developed to efficiently investigate complex orthology relationships. Cross-species expression analysis revealed that the integration of complementary data types extended the scope of complex orthology relationships, especially between more distantly related species. Finally, based on phylogenetic profiling, we propose a set of core gene families within the green plant lineage that will be instrumental to assess the gene space of draft or newly sequenced plant genomes during the assembly or annotation phase.     

The animal in the genome: comparative genomics and evolution

Comparisons between completely sequenced metazoan genomes have generally emphasized how similar their encoded protein content is, even when the comparison is between phyla. Given the manifest differences between phyla and, in particular, intuitive notions that some animals are more complex than others, this creates something of a paradox. Simplistic explanations have included arguments such as increased numbers of genes; greater numbers of protein products produced through alternative splicing; increased numbers of regulatory non-coding RNAs and increased complexity of the cis-regulatory code. An obvious value of complete genome sequences lies in their ability to provide us with inventories of such components. I examine progress being made in linking genome content to the pattern of animal evolution, and argue that the gap between genomic and phenotypic complexity can only be understood through the totality of interacting components.     

Rickettsial evolution in the light of comparative genomics

Rickettsia are best known as strictly intracellular vector‐borne bacteria that cause mild to severe diseases in humans and other animals. Recent advances in molecular tools and biological experiments have unveiled a wide diversity of Rickettsia spp. that include species with a broad host range and some species that act as endosymbiotic associates. Molecular phylogenies of Rickettsia spp. contain some ambiguities, such as the position of R. canadensis and relationships within the spotted fever group. In the modern era of genomics, with an ever‐increasing number of sequenced genomes, there is enhanced interest in the use of whole‐genome sequences to understand pathogenesis and assess evolutionary relationships among rickettsial species. Rickettsia have small genomes (1.1–1.5 Mb) as a result of reductive evolution. These genomes contain split genes, gene remnants and pseudogenes that, owing to the colinearity of some rickettsial genomes, may represent different steps of the genome degradation process. Genomics reveal extreme genome reduction and massive gene loss in highly vertebrate‐pathogenic Rickettsia compared to less virulent or endosymbiotic species. Information gleaned from rickettsial genomics challenges traditional concepts of pathogenesis that focused primarily on the acquisition of virulence factors. Another intriguing phenomenon about the reduced rickettsial genomes concerns the large fraction of non‐coding DNA and possible functionality of these “non‐coding” sequences, because of the high conservation of these regions. Despite genome streamlining, Rickettsia spp. contain gene families, selfish DNA, repeat palindromic elements and genes encoding eukaryotic‐like motifs. These features participate in sequence and functional diversity and may play a crucial role in adaptation to the host cell and pathogenesis. Genome analyses have identified a large fraction of mobile genetic elements, including plasmids, suggesting the possibility of lateral gene transfer in these intracellular bacteria. Phylogenetic analyses have identified several candidates for horizontal gene acquisition among Rickettsia spp. including tra, pat2, and genes encoding for the type IV secretion system and ATP/ADP translocase that may have been acquired from bacteria living in amoebae. Gene loss, gene duplication, DNA repeats and lateral gene transfer all have shaped rickettsial genome evolution. A comprehensive analysis of the entire genome, including genes and non‐coding DNA, will help to unlock the mysteries of rickettsial evolution and pathogenesis.     

The ABC's of comparative genomics in the Brassicaceae: building blocks of crucifer genomes

In this review we summarize recent advances in our understanding of phylogenetics, polyploidization and comparative genomics in the family Brassicaceae. These findings pave the way for a unified comparative genomic framework. We integrate several of these findings into a simple system of 24 conserved chromosomal blocks (labeled A-X). The naming, order, orientation and color-coding of these blocks are based on their positions in a proposed ancestral karyotype (n=8), rather than by their position in the reduced genome of Arabidopsis thaliana (n=5). We show how these crucifer building blocks can be rearranged to model the genome structures of A. thaliana, Arabidopsis lyrata, Capsella rubella and Brassica rapa. A framework for comparison between species is timely because several crucifer genome-sequencing projects are underway.     

The multiple facets of homology and their use in comparative genomics to study the evolution of genes, genomes, and species

The incredible development of comparative genomics during the last decade has required a correct use of the concept of homology that was previously utilized only by evolutionary biologists. Unhappily, this concept has been often misunderstood and thus misused when exploited outside its evolutionary context. This review brings back to the correct definition of homology and explains how this definition has been progressively refined in order to adapt it to the various new kinds of analysis of gene properties and of their products that appear with the progress of comparative genomics. Then, we illustrate the power and the proficiency of such a concept when using the available genomics data in order to study the evolution of individual genes, of entire genomes and of species, respectively. After explaining how we detect homologues by an exhaustive comparison of a hundred of complete proteomes, we describe three main lines of research we have developed in the recent years. The first one exploits synteny and gene context data to better understand the mechanisms of genome evolution in prokaryotes. The second one is based on phylogenomics approaches to reconstruct the tree of life. The last one is devoted to reminding that protein homology is often limited to structural segments (SOH=segment of homology or module). Detecting and numbering modules allows tracing back protein history by identifying the events of gene duplication and gene fusion. We insist that one of the main present difficulties in such studies is a lack of a reliable method to identify genuine orthologues. Finally, we show how these homology studies are helpful to annotate genes and genomes and to study the complexity of the relationships between sequence and function of a gene.     

The role of selection in the evolution of human mitochondrial genomes

High mutation rate in mammalian mitochondrial DNA generates a highly divergent pool of alleles even within species that have dispersed and expanded in size recently. Phylogenetic analysis of 277 human mitochondrial genomes revealed a significant (P < 0.01) excess of rRNA and nonsynonymous base substitutions among hotspots of recurrent mutation. Most hotspots involved transitions from guanine to adenine that, with thymine-to-cytosine transitions, illustrate the asymmetric bias in codon usage at synonymous sites on the heavy-strand DNA. The mitochondrion-encoded tRNAThr varied significantly more than any other tRNA gene. Threonine and valine codons were involved in 259 of the 414 amino acid replacements observed. The ratio of nonsynonymous changes from and to threonine and valine differed significantly (P = 0.003) between populations with neutral (22/58) and populations with significantly negative Tajima's D values (70/76), independent of their geographic location. In contrast to a recent suggestion that the excess of nonsilent mutations is characteristic of Arctic populations, implying their role in cold adaptation, we demonstrate that the surplus of nonsynonymous mutations is a general feature of the young branches of the phylogenetic tree, affecting also those that are found only in Africa. We introduce a new calibration method of the mutation rate of synonymous transitions to estimate the coalescent times of mtDNA haplogroups.     

Detection of gene duplications and block duplications in eukaryotic genomes

Several eukaryotic genomes have been completely sequenced and this provides an opportunity to investigate the extent and characteristics (e.g., single gene duplication, block duplication, etc.) of gene duplication in a genome. Detecting duplicate genes in a genome, however, is not a simple problem because of several complications such as domain shuffling, the existence of isoforms derived from alternative splicing, and annotational errors in the databases. We describe a method for overcoming these difficulties and the extents of gene duplication in the genomes of Drosophila melanogaster, Caenorhabditis elegans, and yeast inferred from this method. We also describe a method for detecting block duplications in a genome. Application of this method showed that block duplication is a common phenomenon in both yeast and nematode. The patterns of block duplication in the two species are, however, markedly different. Yeast shows much more extensive block duplication than nematode, with some chromosomes having more than 40% of the duplications derived from block duplications. Moreover, in yeast the majority of block duplications occurred between chromosomes, while in nematode most block duplications occurred within chromosomes.     

The evolution of mycobacterial pathogenicity: clues from comparative genomics.

Comparative genomics, and related technologies, are helping to unravel the molecular basis of the pathogenesis, host range, evolution and phenotypic differences of the slow-growing mycobacteria. In the highly conserved Mycobacterium tuberculosis complex, where single-nucleotide polymorphisms are rare, insertion and deletion events (InDels) are the principal source of genome plasticity. InDels result from recombinational or insertion sequence (IS)-mediated events, expansion of repetitive DNA sequences, or replication errors based on repetitive motifs that remove blocks of genes or contract coding sequences. Comparative genomic analyses also suggest that loss of genes is part of the ongoing evolution of the slow-growing mycobacterial pathogens and might also explain how the vaccine strain BCG became attenuated.     

Study of intrachromosomal duplications among the eukaryote genomes.

Complete eukaryote chromosomes were investigated for intrachromosomal duplications of nucleotide sequences. The analysis was performed by looking for nonexact repeats on two complete genomes, Saccharomyces cerevisiae and Caenorhabditis elegans, and four partial ones, Drosophila melanogaster, Plasmodium falciparum, Arabidopsis thaliana, and Homo sapiens. Through this analysis, we show that all eukaryote chromosomes exhibit similar characteristics for their intrachromosomal repeats, suggesting similar dynamics: many direct repeats have their two copies physically close together, and these close direct repeats are more similar and shorter than the other repeats. On the contrary, there are almost no close inverted repeats. These results support a model for the dynamics of duplication. This model is based on a continuous genesis of tandem repeats and implies that most of the distant and inverted repeats originate from these tandem repeats by further chromosomal rearrangements (insertions, inversions, and deletions). Remnants of these predicted rearrangements have been brought out through fine analysis of the chromosome sequence. Despite these dynamics, shared by all eukaryotes, each genome exhibits its own style of intrachromosomal duplication: the density of repeated elements is similar in all chromosomes issued from the same genome, but is different between species. This density was further related to the relative rates of duplication, deletion, and mutation proper to each species. One should notice that the density of repeats in the X chromosome of C. elegans is much lower than in the autosomes of that organism, suggesting that the exchange between homologous chromosomes is important in the duplication process.     

The latest buzz in comparative genomics

A second species of fruit fly has just been added to the growing list of organisms with complete and annotated genome sequences. The publication of the Drosophila pseudoobscura sequence provides a snapshot of how genomes have changed over tens of millions of years and sets the stage for the analysis of more fly genomes.     

The quest for natural selection in the age of comparative genomics

Continued genome sequencing has fueled progress in statistical methods for understanding the action of natural selection at the molecular level. This article reviews various statistical techniques (and their applicability) for detecting adaptation events and the functional divergence of proteins. As large-scale automated studies become more frequent, they provide a useful resource for generating biological null hypotheses for further experimental and statistical testing. Furthermore, they shed light on typical patterns of lineage-specific evolution of organisms, on the functional and structural evolution of protein families and on the interplay between the two. More complex models are being developed to better reflect the underlying biological and chemical processes and to complement simpler statistical models. Linking molecular processes to their statistical signatures in genomes can be demanding, and the proper application of statistical models is discussed.