Do disparate mechanisms of duplication add similar genes to the genome?

Gene duplication is the fundamental source of new genes. Biases in duplication have profound implications for the dynamics of gene content during evolution. In this article, we compare genes arising from whole gene duplication (WGD), smaller scale duplication (SSD) and singletons in Saccharomyces cerevisiae. Our results demonstrate that genes duplicated by WGD and SSD are similarly biased with respect to codon bias and evolutionary rate, although differing significantly in their functional constituency.     

Two-phase resolution of polyploidy in the Arabidopsis metabolic network gives rise to relative and absolute dosage constraints

The abundance of detected ancient polyploids in extant genomes raises questions regarding evolution after whole-genome duplication (WGD). For instance, what rules govern the preservation or loss of the duplicated genes created by WGD? We explore this question by contrasting two possible preservation forces: selection on relative and absolute gene dosages. Constraints on the relative dosages of central network genes represent an important force for maintaining duplicates (the dosage balance hypothesis). However, preservation may also result from selection on the absolute abundance of certain gene products. The metabolic network of the model plant Arabidopsis thaliana is a powerful system for comparing these hypotheses. We analyzed the surviving WGD-produced duplicate genes in this network, finding evidence that the surviving duplicates from the most recent WGD (WGD-α) are clustered in the network, as predicted by the dosage balance hypothesis. A flux balance analysis suggests an association between the survival of duplicates from a more ancient WGD (WGD-β) and reactions with high metabolic flux. We argue for an interplay of relative and absolute dosage constraints, such that the relative constraints imposed by the recent WGD are still being resolved by evolution, while they have been essentially fully resolved for the ancient event.     

Evolution of vertebrate tissues driven by differential modes of gene duplication

In this study, we investigated the evolution of vertebrate tissues by examining the potential association among gene expression, duplication, and base substitution patterns. In particular, we compared whole-genome duplication (WGD) with small-scale duplication (SSD), as well as tissue restricted with ubiquitously expressed genes. All patterns were also analysed in the light of gene evolutionary rates. Among those genes characterized by rapid evolution and expressed in a restricted range of tissues, SSD was represented in a larger proportion than WGD. Conversely, genes with ubiquitous expression were associated with slower evolutionary rates and a larger proportion of WGD. The results also show that evolutionary rates were faster in genes expressed in endodermal tissues and slower in ectodermal genes. Accordingly, the proportion of the SSD and WGD genes was highest in the endoderm and ectoderm, respectively. Therefore, quickly evolving SSD genes might have contributed to the faster evolution of endodermal tissues, whereas the comparatively slowly evolving WGD genes might have functioned to maintain the basic characteristics of ectodermal tissues. Mesenchymal tissues occupied an intermediate position in this regard, whereas the patterns observed for haemocytes were unique. Rapid tissue evolution could be related to a specific gene duplication mode (SSD) and faster molecular evolution in response to exposure to the external environment. These findings reveal general patterns underlying the evolution of tissues and their corresponding genes.     

Whole-genome duplications spurred the functional diversification of the globin gene superfamily in vertebrates

It has been hypothesized that two successive rounds of whole-genome duplication (WGD) in the stem lineage of vertebrates provided genetic raw materials for the evolutionary innovation of many vertebrate-specific features. However, it has seldom been possible to trace such innovations to specific functional differences between paralogous gene products that derive from a WGD event. Here, we report genomic evidence for a direct link between WGD and key physiological innovations in the vertebrate oxygen transport system. Specifically, we demonstrate that key globin proteins that evolved specialized functions in different aspects of oxidative metabolism (hemoglobin, myoglobin, and cytoglobin) represent paralogous products of two WGD events in the vertebrate common ancestor. Analysis of conserved macrosynteny between the genomes of vertebrates and amphioxus (subphylum Cephalochordata) revealed that homologous chromosomal segments defined by myoglobin + globin-E, cytoglobin, and the α-globin gene cluster each descend from the same linkage group in the reconstructed proto-karyotype of the chordate common ancestor. The physiological division of labor between the oxygen transport function of hemoglobin and the oxygen storage function of myoglobin played a pivotal role in the evolution of aerobic energy metabolism, supporting the hypothesis that WGDs helped fuel key innovations in vertebrate evolution.     

Protein under-wrapping causes dosage sensitivity and decreases gene duplicability

A fundamental issue in molecular evolution is how to identify the evolutionary forces that determine the fate of duplicated genes. The dosage balance hypothesis has been invoked to explain gene duplication patterns at the genomic level under the premise that a dosage imbalance among protein-complex subunits or interacting partners is often deleterious. Here we examine this hypothesis by investigating the molecular basis of dosage sensitivity. We focus on the extent of protein wrapping, which indicates how strongly the structural integrity of a protein relies on its interactive context. From this perspective, we predict that the duplicates of a highly under-wrapped protein or protein subunit should (1) be more sensitive to dosage imbalance and be less likely to be retained and (2) be more likely to survive from a whole-genome duplication (WGD) than from a non-WGD because a WGD causes little or no dosage imbalance. Our under-wrapping analysis of more than 12,000 protein structures strongly supports these predictions and further reveals that the effect of dosage sensitivity on gene duplicability decreases with increasing organismal complexity.     

Genes encoding hub and bottleneck enzymes of the Arabidopsis metabolic network preferentially retain homeologs through whole genome duplication

Background

Whole genome duplication (WGD) occurs widely in angiosperm evolution. It raises the intriguing question of how interacting networks of genes cope with this dramatic evolutionary event.

Results

In study of the Arabidopsis metabolic network, we assigned each enzyme (node) with topological centralities (in-degree, out-degree and between-ness) to measure quantitatively their centralities in the network. The Arabidopsis metabolic network is highly modular and separated into 11 interconnected modules, which correspond well to the functional metabolic pathways. The enzymes with higher in-out degree and between-ness (defined as hub and bottleneck enzymes, respectively) tend to be more conserved and preferentially retain homeologs after WGD. Moreover, the simultaneous retention of homeologs encoding enzymes which catalyze consecutive steps in a pathway is highly favored and easily achieved, and enzyme-enzyme interactions contribute to the retention of one-third of WGD enzymes.

Conclusions

Our analyses indicate that the hub and bottleneck enzymes of metabolic network obtain great benefits from WGD, and this event grants clear evolutionary advantages in adaptation to different environments.     

Functional analysis of gene duplications in Saccharomyces cerevisiae

Gene duplication can occur on two scales: whole-genome duplications (WGD) and smaller-scale duplications (SSD) involving individual genes or genomic segments. Duplication may result in functionally redundant genes or diverge in function through neofunctionalization or subfunctionalization. The effect of duplication scale on functional evolution has not yet been explored, probably due to the lack of global knowledge of protein function and different times of duplication events. To address this question, we used integrated Bayesian analysis of diverse functional genomic data to accurately evaluate the extent of functional similarity and divergence between paralogs on a global scale. We found that paralogs resulting from the whole-genome duplication are more likely to share interaction partners and biological functions than smaller-scale duplicates, independent of sequence similarity. In addition, WGD paralogs show lower frequency of essential genes and higher synthetic lethality rate, but instead diverge more in expression pattern and upstream regulatory region. Thus, our analysis demonstrates that WGD paralogs generally have similar compensatory functions but diverging expression patterns, suggesting a potential of distinct evolutionary scenarios for paralogs that arose through different duplication mechanisms. Furthermore, by identifying these functional disparities between the two types of duplicates, we reconcile previous disputes on the relationship between sequence divergence and expression divergence or essentiality.     

GPCR genes are preferentially retained after whole genome duplication

One of the most interesting questions in biology is whether certain pathways have been favored during evolution, and if so, what properties could cause such a preference. Due to the lack of experimental evidence, whether select gene families have been preferentially retained over time after duplication in metazoan organisms remains unclear. Here, by syntenic mapping of nonchemosensory G protein-coupled receptor genes (nGPCRs which represent half the receptome for transmembrane signaling) in the vertebrate genomes, we found that, as opposed to the 8-15% retention rate for whole genome duplication (WGD)-derived gene duplicates in the entire genome of pufferfish, greater than 27.8% of WGD-derived nGPCRs which interact with a nonpeptide ligand were retained after WGD in pufferfish Tetraodon nigroviridis. In addition, we show that concurrent duplication of cognate ligand genes by WGD could impose selection of nGPCRs that interact with a polypeptide ligand. Against less than 2.25% probability for parallel retention of a pair of WGD-derived ligands and a pair of cognate receptor duplicates, we found a more than 8.9% retention of WGD-derived ligand-nGPCR pairs--threefold greater than one would surmise. These results demonstrate that gene retention is not uniform after WGD in vertebrates, and suggest a Darwinian selection of GPCR-mediated intercellular communication in metazoan organisms.     

Functional Divergence in a Multi-gene Family Is a Key Evolutionary Innovation for Anaerobic Growth in Saccharomyces cerevisiae

The amplification and diversification of genes into large multi-gene families often mark key evolutionary innovations, but this process often creates genetic redundancy that hinders functional investigations. When the model budding yeast Saccharomyces cerevisiae transitions to anaerobic growth conditions, the cell massively induces the expression of seven serine/threonine-rich anaerobically-induced cell wall mannoproteins (anCWMPs): TIP1, TIR1, TIR2, TIR3, TIR4, DAN1, and DAN4. Here, we show that these genes likely derive evolutionarily from a single ancestral anCWMP locus, which was duplicated and translocated to new genomic contexts several times both prior to and following the budding yeast whole genome duplication (WGD) event. Based on synteny and their phylogeny, we separate the anCWMPs into four gene subfamilies. To resolve prior inconclusive genetic investigations of these genes, we constructed a set of combinatorial deletion mutants to determine their contributions toward anaerobic growth in S. cerevisiae. We found that two genes, TIR1 and TIR3, were together necessary and sufficient for the anCWMP contribution to anaerobic growth. Overexpressing either gene alone was insufficient for anaerobic growth, implying that they encode non-overlapping functional roles in the cell during anaerobic growth. We infer from the phylogeny of the anCWMP genes that these two important genes derive from an ancient duplication that predates the WGD event, whereas the TIR1 subfamily experienced gene family amplification after the WGD event. Taken together, the genetic and molecular evidence suggests that one key anCWMP gene duplication event, several auxiliary gene duplication events, and functional divergence underpin the evolution of anaerobic growth in budding yeasts.     

Probabilistic cross-species inference of orthologous genomic regions created by whole-genome duplication in yeast

Identification of orthologous genes across species becomes challenging in the presence of a whole-genome duplication (WGD). We present a probabilistic method for identifying orthologs that considers all possible orthology/paralogy assignments for a set of genomes with a shared WGD (here five yeast species). This approach allows us to estimate how confident we can be in the orthology assignments in each genomic region. Two inferences produced by this model are indicative of purifying selection acting to prevent duplicate gene loss. First, our model suggests that there are significant differences (up to a factor of seven) in duplicate gene half-life. Second, we observe differences between the genes that the model infers to have been lost soon after WGD and those lost more recently. Gene losses soon after WGD appear uncorrelated with gene expression level and knockout fitness defect. However, later losses are biased toward genes whose paralogs have high expression and large knockout fitness defects, as well as showing biases toward certain functional groups such as ribosomal proteins. We suggest that while duplicate copies of some genes may be lost neutrally after WGD, another set of genes may be initially preserved in duplicate by natural selection for reasons including dosage.     

Factors that contribute to variation in evolutionary rate among Arabidopsis genes

Surprisingly, few studies have described evolutionary rate variation among plant nuclear genes, with little investigation of the causes of rate variation. Here, we describe evolutionary rates for 11,492 ortholog pairs between Arabidopsis thaliana and A. lyrata and investigate possible contributors to rate variation among these genes. Rates of evolution at synonymous sites vary along chromosomes, suggesting that mutation rates vary on genomic scales, perhaps as a function of recombination rate. Rates of evolution at nonsynonymous sites correlate most strongly with expression patterns, but they also vary as to whether a gene is duplicated and retained after a whole-genome duplication (WGD) event. WGD genes evolve more slowly, on average, than nonduplicated genes and non-WGD duplicates. We hypothesize that levels and patterns of expression are not only the major determinants that explain nonsynonymous rate variation among genes but also a critical determinant of gene retention after duplication.     

Rate asymmetry after genome duplication causes substantial long-branch attraction artifacts in the phylogeny of Saccharomyces species

Whole-genome duplication (WGD) produces sets of gene pairs that are all of the same age. We therefore expect that phylogenetic trees that relate these pairs to their orthologs in other species should show a single consistent topology. However, a previous study of gene pairs formed by WGD in the yeast Saccharomyces cerevisiae found conflicting topologies among neighbor-joining (NJ) trees drawn from different loci and suggested that this conflict was the result of "asynchronous functional divergence" of duplicated genes (Langkjaer, R. B., P. F. Cliften, M. Johnston, and J. Piskur. 2003. Yeast genome duplication was followed by asynchronous differentiation of duplicated genes. Nature 421:848-852). Here, we test whether the conflicting topologies might instead be due to asymmetrical rates of evolution leading to long-branch attraction (LBA) artifacts in phylogenetic trees. We constructed trees for 433 pairs of WGD paralogs in S. cerevisiae with their single orthologs in Saccharomyces kluyveri and Candida albicans. We find a strong correlation between the asymmetry of evolutionary rates of a pair of S. cerevisiae paralogs and the topology of the tree inferred for that pair. Saccharomyces cerevisiae gene pairs with approximately equal rates of evolution tend to give phylogenies in which the WGD postdates the speciation between S. cerevisiae and S. kluyveri (B-trees), whereas trees drawn from gene pairs with asymmetrical rates tend to show WGD pre-dating this speciation (A-trees). Gene order data from throughout the genome indicate that the "A-trees" are artifacts, even though more than 50% of gene pairs are inferred to have this topology when the NJ method as implemented in ClustalW (i.e., with Poisson correction of distances) is used to construct the trees. This LBA artifact can be ameliorated, but not eliminated, by using gamma-corrected distances or by using maximum likelihood trees with robustness estimated by the Shimodaira-Hasegawa test. Tests for adaptive evolution indicated that positive selection might be the cause of rate asymmetry in a substantial fraction (19%) of the paralog pairs.     

水稻和其他禾本科植物基因组多倍体起源的证据

基因加倍(Gene duplication)被认为是进化的加速器。古老的基因组加倍事件已经在多个物种中被确定,包括酵母、脊椎动物以及拟南芥等。本研究发现水稻基因组同样存在全基因组加倍事件,大概发生在禾谷类作物分化之前,距今约7000万年。在水稻基因组中,共找到117个加倍区段(Duplicated block),分布在水稻的全部12条染色体,覆盖约60％的水稻基因组。在加倍区段,大约有20％的基因保留了加倍后的姊妹基因对(Duplicated pairs)。与此形成鲜明对照的是加倍区段的转录因子保留了60％的姊妹基因。禾本科植物全基因组加倍事件的确定对研究禾本科植物基因组的进化具有重要影响,暗示了多倍体化及随后的基因丢失、染色体重排等在禾谷类物种分化中扮演了重要角色。     

Rapid, repeated, and clustered loss of duplicate genes in allopolyploid plant populations of independent origin

The predictability of evolution is debatable, with recent evidence suggesting that outcomes may be constrained by gene interaction networks [1]. Whole-genome duplication (WGD; polyploidization-ubiquitous in plant evolution [2]) provides the opportunity to evaluate the predictability of genome reduction, a pervasive feature of evolution [3, 4]. Repeated patterns of genome reduction appear to have occurred via duplicated gene (homeolog) loss in divergent species following ancient WGD [5-9], with evidence for preferential retention of duplicates in certain gene classes [8-10]. The speed at which these patterns arise is unknown. We examined presence/absence of 70 homeologous loci in 59 Tragopogon miscellus plants from five natural populations of independent origin; this allotetraploid arose ~80 years ago via hybridization between diploid parents and WGD [11]. Genes were repeatedly retained or lost in clusters, and the gene ontology categories of the missing genes correspond to those lost after ancient WGD in the same family (Asteraceae; sunflower family) [6] and with gene dosage sensitivity [8]. These results provide evidence that the outcomes of WGD are predictable, even in 40 generations, perhaps due to the connectivity of gene products [8, 10, 12]. The high frequency of single-allele losses detected and low frequency of changes fixed within populations provide evidence for ongoing evolution.     

When everything changes at once: finding a new normal after genome duplication

Whole-genome duplication (WGD), which leads to polyploidy, is implicated in adaptation and speciation. But what are the immediate effects of WGD and how do newly polyploid lineages adapt to them? With many studies of new and evolved polyploids now available, along with studies of genes under selection in polyploids, we are in an increasingly good position to understand how polyploidy generates novelty. Here, I will review consistent effects of WGD on the biology of plants, such as an increase in cell size, increased stress tolerance and more. I will discuss how a change in something as fundamental as cell size can challenge the function of some cell types in particular. I will also discuss what we have learned about the short- to medium-term evolutionary response to WGD. It is now clear that some of this evolutionary response may ‘lock in’ traits that happen to be beneficial, while in other cases, it might be more of an ‘emergency response’ to work around physiological changes that are either deleterious, or cannot be undone in the polyploid context. Yet, other traits may return rapidly to a diploid-like state. Polyploids may, by re-jigging many inter-related processes, find a new, conditionally adaptive, normal.     

Exonic remnants of whole-genome duplication reveal cis-regulatory function of coding exons

Using a comparative genomics approach to reconstruct the fate of genomic regulatory blocks (GRBs) and identify exonic remnants that have survived the disappearance of their host genes after whole-genome duplication (WGD) in teleosts, we discover a set of 38 candidate cis-regulatory coding exons (RCEs) with predicted target genes. These elements demonstrate evolutionary separation of overlapping protein-coding and regulatory information after WGD in teleosts. We present evidence that the corresponding mammalian exons are still under both coding and non-coding selection pressure, are more conserved than other protein coding exons in the host gene and several control sets, and share key characteristics with highly conserved non-coding elements in the same regions. Their dual function is corroborated by existing experimental data. Additionally, we show examples of human exon remnants stemming from the vertebrate 2R WGD. Our findings suggest that long-range cis-regulatory inputs for developmental genes are not limited to non-coding regions, but can also overlap the coding sequence of unrelated genes. Thus, exonic regulatory elements in GRBs might be functionally equivalent to those in non-coding regions, calling for a re-evaluation of the sequence space in which to look for long-range regulatory elements and experimentally test their activity.     

The fate of the duplicated androgen receptor in fishes: a late neofunctionalization event?

Background  

Based on the observation of an increased number of paralogous genes in teleost fishes compared with other vertebrates and on the conserved synteny between duplicated copies, it has been shown that a whole genome duplication (WGD) occurred during the evolution of Actinopterygian fish. Comparative phylogenetic dating of this duplication event suggests that it occurred early on, specifically in teleosts. It has been proposed that this event might have facilitated the evolutionary radiation and the phenotypic diversification of the teleost fish, notably by allowing the sub- or neo-functionalization of many duplicated genes.