Striking Similarities in the Genomic Distribution of Tandemly Arrayed Genes in Arabidopsis and Rice

In Arabidopsis, tandemly arrayed genes (TAGs) comprise >10% of the genes in the genome. These duplicated genes represent a rich template for genetic innovation, but little is known of the evolutionary forces governing their generation and maintenance. Here we compare the organization and evolution of TAGs between Arabidopsis and rice, two plant genomes that diverged ~150 million years ago. TAGs from the two genomes are similar in a number of respects, including the proportion of genes that are tandemly arrayed, the number of genes within an array, the number of tandem arrays, and the dearth of TAGs relative to single copy genes in centromeric regions. Analysis of recombination rates along rice chromosomes confirms a positive correlation between the occurrence of TAGs and recombination rate, as found in Arabidopsis. TAGs are also biased functionally relative to duplicated, nontandemly arrayed genes. In both genomes, TAGs are enriched for genes that encode membrane proteins and function in “abiotic and biotic stress” but underrepresented for genes involved in transcription and DNA or RNA binding functions. We speculate that these observations reflect an evolutionary trend in which successful tandem duplication involves genes either at the end of biochemical pathways or in flexible steps in a pathway, for which fluctuation in copy number is unlikely to affect downstream genes. Despite differences in the age distribution of tandem arrays, the striking similarities between rice and Arabidopsis indicate similar mechanisms of TAG generation and maintenance.

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title: Molecular Clocks and Nucleotide Substitution Rates in Higher Plants
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abstract: While the presence/absence polymorphism is commonly observed in disease resistance (R-) genes in Arabidopsis, only a few R-genes under the presence/absence polymorphism (R-P/A) have been investigated. To understand the mechanism of the molecular evolution of R-P/A, we investigated genetic variation of nine R-P/A in A. thaliana from worldwide populations. The number of possessed R-genes varied widely among accessions (two to nine, on average 4.3 ± 1.6/accession). No pair of accessions shared the same haplotype, and no clear geographic differentiation was observed with respect to the pattern of presence/absence of the R-genes investigated. Presence allele frequencies also varied among loci (25–70%), and no linkage disequilibrium was detected among them. Although the LRR region in regular R-genes is known to be highly polymorphic and has a high Ka/Ks ratio in A. thaliana, nucleotide sequences of this region in the R-P/A showed a relatively low level of genetic variation (π = 0.0002–0.016) and low Ka/Ks (0.03–0.70, <1). In contrast, the nucleotide diversities around the deletion junction of R-P/A were constantly high between presence and absence accessions for the R-genes (Dxy = 0.031–0.103). Our results suggest that R-P/A loci evolved differently from other R-gene loci and that balancing selection plays an important role in molecular evolution of R-P/A.

title: Bias of Selection on Human Copy-Number Variants
abstract: Although large-scale copy-number variation is an important contributor to conspecific genomic diversity, whether these variants frequently contribute to human phenotype differences remains unknown. If they have few functional consequences, then copy-number variants (CNVs) might be expected both to be distributed uniformly throughout the human genome and to encode genes that are characteristic of the genome as a whole. We find that human CNVs are significantly overrepresented close to telomeres and centromeres and in simple tandem repeat sequences. Additionally, human CNVs were observed to be unusually enriched in those protein-coding genes that have experienced significantly elevated synonymous and nonsynonymous nucleotide substitution rates, estimated between single human and mouse orthologues. CNV genes encode disproportionately large numbers of secreted, olfactory, and immunity proteins, although they contain fewer than expected genes associated with Mendelian disease. Despite mouse CNVs also exhibiting a significant elevation in synonymous substitution rates, in most other respects they do not differ significantly from the genomic background. Nevertheless, they encode proteins that are depleted in olfactory function, and they exhibit significantly decreased amino acid sequence divergence. Natural selection appears to have acted discriminately among human CNV genes. The significant overabundance, within human CNVs, of genes associated with olfaction, immunity, protein secretion, and elevated coding sequence divergence, indicates that a subset may have been retained in the human population due to the adaptive benefit of increased gene dosage. By contrast, the functional characteristics of mouse CNVs either suggest that advantageous gene copies have been depleted during recent selective breeding of laboratory mouse strains or suggest that they were preferentially fixed as a consequence of the larger effective population size of wild mice. It thus appears that CNV differences among mouse strains do not provide an appropriate model for large-scale sequence variations in the human population.

title: On the formation of novel genes by duplication in the Caenorhabditis elegans genome.
abstract: Gene duplication is thought to play the singular most important role in the formation of novel genes. The canonical model of gene duplication postulates that novel genes arise in a two-step fashion, namely, (1) the complete duplication of a gene followed by (2) the gradual accumulation of mutations in one or both copies leading to an altered function. It was previously demonstrated that more than 50% of newborn duplicates in Caenorhabditis elegans had unique exons in one or both members of a duplicate pair, indicating that many duplicates are not functionally identical to the progenitor copy at birth. Both partial and chimeric gene duplications contribute to the formation of novel genes. For chimeric duplications, the genomic sources of unique exons are diverse, including genic and intergenic regions, as well as repetitive elements. These novel genes derived from partial and chimeric duplications are equally likely to be transcriptionally active as copies derived from complete duplications of the ancestral gene. Duplication breakpoints in the ancestral copies are uniformly distributed in the genome, ruling out the role of any mechanism that restricts them to a particular type of sequence such as introns. Finally, both intron loss and gain contribute to the differential distribution of introns between two copies.

title: An introduction to population genetics theory
abstract: An introduction to population genetics theory , An introduction to population genetics theory , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی

title: Functional Divergence of Duplicated Genes Formed by Polyploidy during Arabidopsis Evolution
abstract: To study the evolutionary effects of polyploidy on plant gene functions, we analyzed functional genomics data for a large number of duplicated gene pairs formed by ancient polyploidy events in Arabidopsis thaliana. Genes retained in duplicate are not distributed evenly among Gene Ontology or Munich Information Center for Protein Sequences functional categories, which indicates a nonrandom process of gene loss. Genes involved in signal transduction and transcription have been preferentially retained, and those involved in DNA repair have been preferentially lost. Although the two members of each gene pair must originally have had identical transcription profiles, less than half of the pairs formed by the most recent polyploidy event still retain significantly correlated profiles. We identified several cases where groups of duplicated gene pairs have diverged in concert, forming two parallel networks, each containing one member of each gene pair. In these cases, the expression of each gene is strongly correlated with the other nonhomologous genes in its network but poorly correlated with its paralog in the other network. We also find that the rate of protein sequence evolution has been significantly asymmetric in >20% of duplicate pairs. Together, these results suggest that functional diversification of the surviving duplicated genes is a major feature of the long-term evolution of polyploids.

title: An adaptive radiation model for the origin of new gene functions
abstract: Current models for the evolution of new gene functions after gene duplication presume that the duplication events themselves have no effect on fitness. But those duplications that result in new gene functions are likely to be positively selected from their inception. The evolution of new function may start with the amplification of an existing gene with some level of preadaptation for that function, followed by a period of competitive evolution among the gene copies, resulting in the preservation of the most effective variant and the 'pseudogenization' and eventual loss of the rest.

title: Expression pattern shifts following duplication indicative of subfunctionalization and neofunctionalization in regulatory genes of Arabidopsis.
abstract: Gene duplication plays an important role in the evolution of diversity and novel function and is especially prevalent in the nuclear genomes of flowering plants. Duplicate genes may be maintained through subfunctionalization and neofunctionalization at the level of expression or coding sequence. In order to test the hypothesis that duplicated regulatory genes will be differentially expressed in a specific manner indicative of regulatory subfunctionalization and/or neofunctionalization, we examined expression pattern shifts in duplicated regulatory genes in Arabidopsis. A two-way analysis of variance was performed on expression data for 280 phylogenetically identified paralogous pairs. Expression data were extracted from global expression profiles for wild-type root, stem, leaf, developing inflorescence, nearly mature flower buds, and seedpod. Gene, organ, and gene by organ interaction (G x O) effects were examined. Results indicate that 85% of the paralogous pairs exhibited a significant G x O effect indicative of regulatory subfunctionalization and/or neofunctionalization. A significant G x O effect was associated with complementary expression patterns in 45% of pairwise comparisons. No association was detected between a G x O effect and a relaxed evolutionary constraint as detected by the ratio of nonsynonymous to synonymous substitutions. Ancestral gene expression patterns inferred across a Type II MADS-box gene phylogeny suggest several cases of regulatory neofunctionalization and organ-specific nonfunctionalization. Complete linkage clustering of gene expression levels across organs suggests that regulatory modules for each organ are independent or ancestral genes had limited expression. We propose a new classification, regulatory hypofunctionalization, for an overall decrease in expression level in one member of a paralogous pair while still having a significant G x O effect. We conclude that expression divergence specifically indicative of subfunctionalization and/or neofunctionalization contributes to the maintenance of most if not all duplicated regulatory genes in Arabidopsis and hypothesize that this results in increasing expression diversity or specificity of regulatory genes after each round of duplication.

title: Nonrandom divergence of gene expression following gene and genome duplications in the flowering plant Arabidopsis thaliana
abstract: BackgroundGenome analyses have revealed that gene duplication in plants is rampant. Furthermore, many of the duplicated genes seem to have been created through ancient genome-wide duplication events. Recently, we have shown that gene loss is strikingly different for large- and small-scale duplication events and highly biased towards the functional class to which a gene belongs. Here, we study the expression divergence of genes that were created during large- and small-scale gene duplication events by means of microarray data and investigate both the influence of the origin (mode of duplication) and the function of the duplicated genes on expression divergence.ResultsDuplicates that have been created by large-scale duplication events and that can still be found in duplicated segments have expression patterns that are more correlated than those that were created by small-scale duplications or those that no longer lie in duplicated segments. Moreover, the former tend to have highly redundant or overlapping expression patterns and are mostly expressed in the same tissues, while the latter show asymmetric divergence. In addition, a strong bias in divergence of gene expression was observed towards gene function and the biological process genes are involved in.ConclusionBy using microarray expression data for Arabidopsis thaliana, we show that the mode of duplication, the function of the genes involved, and the time since duplication play important roles in the divergence of gene expression and, therefore, in the functional divergence of genes after duplication.

title: Repbase update: a database and an electronic journal of repetitive elements.
abstract: This work was supported in part by the National Library of Medicine, grant 5 P41 LM06252-3.

title: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
abstract: The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.

title: Codon-substitution models for heterogeneous selection pressure at amino acid sites.
abstract: Comparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (omega = d(N)d(S)) is an important indicator of selective pressure at the protein level, with omega = 1 meaning neutral mutations, omega < 1 purifying selection, and omega > 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying omega ratios. We develop models that account for heterogeneous omega ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of omega among sites. In all data sets analyzed, the selective pressure indicated by the omega ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average omega ratio across sites is <1, but in which some sites are clearly under diversifying selection with omega > 1. Genes undergoing positive selection include the beta-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for omega and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of omega among sites from real data sets.

title: Functional Annotation of the Arabidopsis Genome Using Controlled Vocabularies1
abstract: Controlled vocabularies are increasingly used by databases to describe genes and gene products because they facilitate identification of similar genes within an organism or among different organisms. One of The Arabidopsis Information Resource's goals is to associate all Arabidopsis genes with terms developed by the Gene Ontology Consortium that describe the molecular function, biological process, and subcellular location of a gene product. We have also developed terms describing Arabidopsis anatomy and developmental stages and use these to annotate published gene expression data. As of March 2004, we used computational and manual annotation methods to make 85,666 annotations representing 26,624 unique loci. We focus on associating genes to controlled vocabulary terms based on experimental data from the literature and use The Arabidopsis Information Resource-developed PubSearch software to facilitate this process. Each annotation is tagged with a combination of evidence codes, evidence descriptions, and references that provide a robust means to assess data quality. Annotation of all Arabidopsis genes will allow quantitative comparisons between sets of genes derived from sources such as microarray experiments. The Arabidopsis annotation data will also facilitate annotation of newly sequenced plant genomes by using sequence similarity to transfer annotations to homologous genes. In addition, complete and up-to-date annotations will make unknown genes easy to identify and target for experimentation. Here, we describe the process of Arabidopsis functional annotation using a variety of data sources and illustrate several ways in which this information can be accessed and used to infer knowledge about Arabidopsis and other plant species.