Rapid divergence in expression between duplicate genes inferred from microarray data

For more than 30 years, expression divergence has been considered as a major reason for retaining duplicated genes in a genome, but how often and how fast duplicate genes diverge in expression has not been studied at the genomic level. Using yeast microarray data, we show that expression divergence between duplicate genes is significantly correlated with their synonymous divergence (K_S) and also with their nonsynonymous divergence (K_A) if K_A ≤ 0.3. Thus, expression divergence increases with evolutionary time, and K_A is initially coupled with expression divergence. More interestingly, a large proportion of duplicate genes have diverged quickly in expression and the vast majority of gene pairs eventually become divergent in expression. Indeed, more than 40% of gene pairs show expression divergence even when K_S is ≤ 0.10, and this proportion becomes >80% for K_S > 1.5. Only a small fraction of ancient gene pairs do not show expression divergence.     

The monosaccharide transporter gene family in Arabidopsis and rice: a history of duplications, adaptive evolution, and functional divergence

Current hypotheses of gene duplicate divergence propose that surviving members of a gene duplicate pair may evolve, under conditions of purifying or nearly neutral selection, in one of two ways: with new function arising in one duplicate while the other retains original function (neofunctionalization [NF]) or partitioning of the original function between the 2 paralogs (subfunctionalization [SF]). More recent studies propose that SF followed by NF (subneofunctionalization [SNF]) explains the divergence of many duplicate genes. In this analysis, we evaluate these hypotheses in the context of the large monosaccharide transporter (MST) gene families in Arabidopsis and rice. MSTs have an ancient origin, predating plants, and have evolved in the seed plant lineage to comprise 7 subfamilies. In Arabidopsis, 53 putative MST genes have been identified, with one subfamily greatly expanded by tandem gene duplications. We searched the rice genome for members of the MST gene family and compared them with the MST gene family in Arabidopsis to determine subfamily expansion patterns and estimate gene duplicate divergence times. We tested hypotheses of gene duplicate divergence in 24 paralog pairs by comparing protein sequence divergence rates, estimating positive selection on codon sites, and analyzing tissue expression patterns. Results reveal the MST gene family to be significantly larger (65) in rice with 2 subfamilies greatly expanded by tandem duplications. Gene duplicate divergence time estimates indicate that early diversification of most subfamilies occurred in the Proterozoic (2500-540 Myr) and that expansion of large subfamilies continued through the Cenozoic (65-0 Myr). Two-thirds of paralog pairs show statistically symmetric rates of sequence evolution, most consistent with the SF model, with half of those showing evidence for positive selection in one or both genes. Among 8 paralog pairs showing asymmetric divergence rates, most consistent with the NF model, nearly half show evidence of positive selection. Positive selection does not appear in any duplicate pairs younger than approximately 34 Myr. Our data suggest that the NF, SF, and SNF models describe different outcomes along a continuum of divergence resulting from initial conditions of relaxed constraint after duplication.     

Divergence in expression between duplicated genes in Arabidopsis

New genes may arise through tandem duplication, dispersed small-scale duplication, and polyploidy, and patterns of divergence between duplicated genes may vary among these classes. We have examined patterns of gene expression and coding sequence divergence between duplicated genes in Arabidopsis thaliana. Due to the simultaneous origin of polyploidy-derived gene pairs, we can compare covariation in the rates of expression divergence and sequence divergence within this group. Among tandem and dispersed duplicates, much of the divergence in expression profile appears to occur at or shortly after duplication. Contrary to findings from other eukaryotic systems, there is little relationship between expression divergence and synonymous substitutions, whereas there is a strong positive relationship between expression divergence and nonsynonymous substitutions. Because this pattern is pronounced among the polyploidy-derived pairs, we infer that the strength of purifying selection acting on protein sequence and expression pattern is correlated. The polyploidy-derived pairs are somewhat atypical in that they have broader expression patterns and are expressed at higher levels, suggesting differences among polyploidy- and nonpolyploidy-derived duplicates in the types of genes that revert to single copy. Finally, within many of the duplicated pairs, 1 gene is expressed at a higher level across all assayed conditions, which suggests that the subfunctionalization model for duplicate gene preservation provides, at best, only a partial explanation for the patterns of expression divergence between duplicated genes.     

Increased Expression and Protein Divergence in Duplicate Genes Is Associated with Morphological Diversification

The differentiation of both gene expression and protein function is thought to be important as a mechanism of the functionalization of duplicate genes. However, it has not been addressed whether expression or protein divergence of duplicate genes is greater in those genes that have undergone functionalization compared with those that have not. We examined a total of 492 paralogous gene pairs associated with morphological diversification in a plant model organism (Arabidopsis thaliana). Classifying these paralogous gene pairs into high, low, and no morphological diversification groups, based on knock-out data, we found that the divergence rate of both gene expression and protein sequences were significantly higher in either high or low morphological diversification groups compared with those in the no morphological diversification group. These results strongly suggest that the divergence of both expression and protein sequence are important sources for morphological diversification of duplicate genes. Although both mechanisms are not mutually exclusive, our analysis suggested that changes of expression pattern play the minor role (33%–41%) and that changes of protein sequence play the major role (59%–67%) in morphological diversification. Finally, we examined to what extent duplicate genes are associated with expression or protein divergence exerting morphological diversification at the whole-genome level. Interestingly, duplicate genes randomly chosen from A. thaliana had not experienced expression or protein divergence that resulted in morphological diversification. These results indicate that most duplicate genes have experienced minor functionalization.     

Characterization of duplicated Dunaliella viridis SPT1 genes provides insights into early gene divergence after duplication

The sodium-dependent phosphate transporter gene from unicellular green algae Dunaliella viridis, DvSPT1, shares similarity with members of Pi transporter family. Sequencing analysis of D. viridis BAC clone containing the DvSPT1 gene revealed two inverted duplicated copies of this gene (DvSPT1 and DvSPT1-2 respectively). The duplication covered most of both genes except for their 3' downstream region. The duplicated genomic sequences exhibited 97.9% identity with a synonymous divergence of Ks=0.0126 in the coding region. This data indicated very recent gene duplication in D. viridis genome, providing an excellent opportunity to investigate sequence and expression divergence of duplicated genes at an early stage. Scatted point mutations and length polymorphism of simple sequence repeats (SSRs) were predominant among the sequence divergence soon after gene duplication. Due to sequence divergence in the 5' regulatory regions and a swap of the entire 3' downstream regions (3'-UTR), DvSPT1 and DvSPT1-2 showed expression divergence in response to extra-cellular NaCl concentration changes. According to their expression patterns, the two diverged gene copies would provide better adaptation to a broader range of extra-cellular NaCl concentration. Furthermore, Southern blot analysis indicated that there might be a large phosphate transporter gene family in D. viridis.     

Expression diversity and evolutionary dynamics of rice duplicate genes

Duplicate genes are believed to be a major source of new gene functions over evolutionary time. In order to evaluate the evolutionary dynamics of rice duplicate genes, formed principally by paleoployploidization prior to the speciation of the Poaceae family, we have employed a public microarray dataset including 155 gene expression omnibus sample plates and bioinformatics tools. At least 57.4% of old ~70 million years ago (MYA) duplicate gene pairs exhibit divergences in expression over the given experimental set, whereas at least 50.9% of young ~7.7-MYA duplicate gene pairs were shown to be divergent. When grouping the rice duplicate genes according to functional categories, we noted a striking and significant enrichment of divergent duplicate metabolism-associated genes, as compared to that observed in non-divergent duplicate genes. While both non-synonymous substitution (Ka) and synonymous substitution (Ks) values between non- and divergent duplicate gene pairs evidenced significant differences, the Ka/Ks values between them exhibited no significant differences. Interestingly, the average numbers of conserved motifs of the duplicate gene pairs revealed a pattern of decline along with an increase in expression diversity, partially supporting the subfunctionalization model with degenerative complementation in regulatory motifs. Duplicate gene pairs with high local similarity (HLS) segments, which might be formed via conversion between rice paleologs, evidenced higher expression correlations than were observed in the gene pairs without the HLS segments; this probably resulted in an increased likelihood of gene conversion in promoters of the gene pairs harboring HLS segments. More than 60% of the rice gene families exhibited similar high expression diversity between members as compared to that of randomly selected gene pairs. These findings are likely reflective of the evolutionary dynamics of rice duplicate genes for gene retention. An erratum to this article can be found at     

Complete mitochondrial genome sequence from an endangered Indian snake, Python molurus molurus (Serpentes, Pythonidae)

This paper reports the complete mitochondrial genome sequence of an endangered Indian snake, Python molurus molurus (Indian Rock Python). A typical snake mitochondrial (mt) genome of 17258 bp length comprising of 37 genes including the 13 protein coding genes, 22 tRNA genes, and 2 ribosomal RNA genes along with duplicate control regions is described herein. The P. molurus molurus mt. genome is relatively similar to other snake mt. genomes with respect to gene arrangement, composition, tRNA structures and skews of AT/GC bases. The nucleotide composition of the genome shows that there are more A-C % than T-G% on the positive strand as revealed by positive AT and CG skews. Comparison of individual protein coding genes, with other snake genomes suggests that ATP8 and NADH3 genes have high divergence rates. Codon usage analysis reveals a preference of NNC codons over NNG codons in the mt. genome of P. molurus. Also, the synonymous and non-synonymous substitution rates (ka/ks) suggest that most of the protein coding genes are under purifying selection pressure. The phylogenetic analyses involving the concatenated 13 protein coding genes of P. molurus molurus conformed to the previously established snake phylogeny.     

External factors accelerate expression divergence between duplicate genes

We examined the evolution of expression of duplicate genes in Arabidopsis thaliana, by analyzing 512 data sets of gene expression microarrays and 2022 recent duplicate gene pairs. Expression divergence between gene duplicates is significantly greater in response to environmental stress than to developmental processes. A slow rate of expression divergence during development might offer dosage-dependent selective advantage, whereas rapid expression divergence in response to external changes might accelerate adaptation.     

Divergence of Gene Body DNA Methylation and Evolution of Plant Duplicate Genes

It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between duplicate genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of duplicate genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica) genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences) of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for duplicate genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes.     

Characterising protein/detergent complexes by triple-detection size-exclusion chromatography

Background

The number of species with completed genomes, including those with evidence for recent whole genome duplication events has exploded. The recently sequenced Atlantic salmon genome has been through two rounds of whole genome duplication since the divergence of teleost fish from the lineage that led to amniotes. This quadrupoling of the number of potential genes has led to complex patterns of retention and loss among gene families.

Results

Methods have been developed to characterize the interplay of duplicate gene retention processes across both whole genome duplication events and additional smaller scale duplication events. Further, gene expression divergence data has become available as well for Atlantic salmon and the closely related, pre-whole genome duplication pike and methods to describe expression divergence are also presented. These methods for the characterization of duplicate gene retention and gene expression divergence that have been applied to salmon are described.

Conclusions

With the growth in available genomic and functional data, the opportunities to extract functional inference from large scale duplicates using comparative methods have expanded dramatically. Recently developed methods that further this inference for duplicated genes have been described.

     

Gene duplication in the evolution of sexual dimorphism

Males and females share most of the same genes, so selection in one sex will typically produce a correlated response in the other sex. Yet, the sexes have evolved to differ in a multitude of behavioral, morphological, and physiological traits. How did this sexual dimorphism evolve despite the presence of a common underlying genome? We investigated the potential role of gene duplication in the evolution of sexual dimorphism. Because duplication events provide extra genetic material, the sexes each might use this redundancy to facilitate sex‐specific gene expression, permitting the evolution of dimorphism. We investigated this hypothesis at the genome‐wide level in Drosophila melanogaster, using the presence of sex‐biased expression as a proxy for the sex‐specific specialization of gene function. We expected that if sexually antagonistic selection is a potent force acting upon individual genes, duplication will result in paralog families whose members differ in sex‐biased expression. Gene members of the same duplicate family can have different expression patterns in males versus females. In particular, duplicate pairs containing a male‐biased gene are found more frequently than expected, in agreement with previous studies. Furthermore, when the singleton ortholog is unbiased, duplication appears to allow one of the paralog copies to acquire male‐biased expression. Conversely, female‐biased expression is not common among duplicates; fewer duplicate genes are expressed in the female‐soma and ovaries than in the male‐soma and testes. Expression divergence exists more in older than in younger duplicates pairs, but expression divergence does not correlate with protein sequence divergence. Finally, genomic proximity may have an effect on whether paralogs differ in sex‐biased expression. We conclude that the data are consistent with a role of gene duplication in fostering male‐biased, but not female‐biased, gene expression, thereby aiding the evolution of sexual dimorphism.     

The structure and early evolution of recently arisen gene duplicates in the Caenorhabditis elegans genome

The significance of gene duplication in provisioning raw materials for the evolution of genomic diversity is widely recognized, but the early evolutionary dynamics of duplicate genes remain obscure. To elucidate the structural characteristics of newly arisen gene duplicates at infancy and their subsequent evolutionary properties, we analyzed gene pairs with < or =10% divergence at synonymous sites within the genome of Caenorhabditis elegans. Structural heterogeneity between duplicate copies is present very early in their evolutionary history and is maintained over longer evolutionary timescales, suggesting that duplications across gene boundaries in conjunction with shuffling events have at least as much potential to contribute to long-term evolution as do fully redundant (complete) duplicates. The median duplication span of 1.4 kb falls short of the average gene length in C. elegans (2.5 kb), suggesting that partial gene duplications are frequent. Most gene duplicates reside close to the parent copy at inception, often as tandem inverted loci, and appear to disperse in the genome as they age, as a result of reduced survivorship of duplicates located in proximity to the ancestral copy. We propose that illegitimate recombination events leading to inverted duplications play a disproportionately large role in gene duplication within this genome in comparison with other mechanisms.     

The role of cis-regulatory motifs and genetical control of expression in the divergence of yeast duplicate genes

Expression divergence of duplicate genes is widely believedto be important for their retention and evolution of new function,although the mechanism that determines their expression divergenceremains unclear. We use a genetical genomics approach to exploredivergence in genetical control of yeast duplicate genes createdby a whole-genome duplication that occurred about 100 MYA andthose with a younger duplication age. The analysis reveals thatduplicate genes have a significantly higher probability of sharingcommon genetic control than pairs of singleton genes. The expressionquantitative trait loci (eQTLs) have diverged completely fora high proportion of duplicate pairs, whereas a substantiallylarger proportion of duplicates share common regulatory motifsafter 100 Myr of divergent evolution. The similarity in bothgenetical control and cis motif structure for a duplicate pairis a reflection of its evolutionary age. This study revealsthat up to 20% of variation in expression between ancient duplicategene pairs in the yeast genome can be explained by both cismotif divergence (8%) and by trans eQTL divergence (10%). Initially,divergence in all 3 aspects of cis motif structure, trans-geneticalcontrol, and expression evolves coordinately with the codingsequence divergence of both young and old duplicate pairs. Thesefindings highlight the importance of divergence in both cismotif structure and trans-genetical control in the diverse setof mechanisms underlying the expression divergence of yeastduplicate genes.     

Mining EST databases to resolve evolutionary events in major crop species.

Using plant EST collections, we obtained 1392 potential gene duplicates across 8 plant species: Zea mays, Oryza sativa, Sorghum bicolor, Hordeum vulgare, Solanum tuberosum, Lycopersicon esculentum, Medicago truncatula, and Glycine max. We estimated the synonymous and nonsynonymous distances between each gene pair and identified two to three mixtures of normal distributions corresponding to one to three rounds of genome duplication in each species. Within the Poaceae, we found a conserved duplication event among all four species that occurred approximately 50-60 million years ago (Mya); an event that probably occurred before the major radiation of the grasses. In the Solanaceae, we found evidence for a conserved duplication event approximately 50-52 Mya. A duplication in soybean occurred approximately 44 Mya and a duplication in Medicago about 58 Mya. Comparing synonymous and nonsynonymous distances allowed us to determine that most duplicate gene pairs are under purifying, negative selection. We calculated Pearson's correlation coefficients to provide us with a measure of how gene expression patterns have changed between duplicate pairs, and compared this across evolutionary distances. This analysis showed that some duplicates seemed to retain expression patterns between pairs, whereas others showed uncorrelated expression.     

Selection-Driven Divergence After Gene Duplication in Arabidopsis thaliana

Gene duplications are one of the most important mechanisms for the origin of evolutionary novelties. Even though various models of the fate of duplicated genes have been established, current knowledge about the role of divergent selection after gene duplication is rather limited. In this study, we analyzed sequence divergence in response to neo- and subfunctionalization of segmentally duplicated genes in the genome of Arabidopsis thaliana. We compared the genomes of A. thaliana and the poplar Populus trichocarpa to identify orthologous pairs of genes and their corresponding inparalogs. Maximum-likelihood analyses of the nonsynonymous and synonymous substitution rate ratio [Formula: see text] of pairs of A. thaliana inparalogs were used to detect differences in the evolutionary rates of protein coding sequences. We analyzed 1,924 A. thaliana paralogous pairs and our results indicate that around 6.9% show divergent ω values between the lineages for a fraction of sites. We observe an enrichment of regulatory sequences, a reduced level of co-expression and an increased number of substitutions that can be attributed to positive selection based on an McDonald-Kreitman type of analysis. Taken together, these results show that selection after duplication contributes substantially to gene novelties and hence functional divergence in plants.     

Inference of expression-dependent negative selection based on polymorphism and divergence in the human genome

There is a mounting evidence for the correlation between the gene expression pattern and sequence divergence. However, little is known about the relationship between the gene expression pattern and polymorphism. We compiled the gene expression, polymorphism, and divergence data from the public databases of the human genome. The ratios of nonsynonymous (A) to synonymous (S) substitutions in polymorphism and divergence in the human genome were strongly influenced by the expression pattern and breadth of genes and showed strong correlations. Among the tissues we analyzed, the brain-expressed genes have the smallest and the liver-expressed genes have the largest proportion of amino acid changes both in polymorphism and divergence. The analysis implies that negative selection is the primary factor affecting expression-dependent gene evolution and the prevalent but nonuniform distribution of slightly deleterious mutations in the genome. Although the genes under relaxed negative selection evolved faster than the other genes, these genes are even more liable to slightly deleterious mutations in the population. On the other hand, nonneutral mutations in the highly conservative genes, such as brain-expressed and housekeeping genes, are largely deleterious and eliminated before they enter the population.