Enhanced fixation and preservation of a newly arisen duplicate gene by masking deleterious loss-of-function mutations

SummarySegmental duplications are enriched within many eukaryote genomes, and their potential consequence is gene duplication. While previous theoretical studies of gene duplication have mainly focused on the gene silencing process after fixation, the process leading to fixation is even more important for segmental duplications, because the majority of duplications would be lost before reaching a significant frequency in a population. Here, by a series of computer simulations, we show that purifying selection against loss-of-function mutations increases the fixation probability of a new duplicate gene, especially when the gene is haplo-insufficient. Theoretically, the probability of simultaneous preservation of both duplicate genes becomes twice the loss-of-function mutation rate (uc) when the population size (N), the degree of dominance of mutations (h) and the recombination rate between the duplicate genes (c) are all sufficiently large (Nuc>1, h>0·1 and c>uc). The preservation probability declines rapidly with h and becomes 0 when h=0 (haplo-sufficiency). We infer that masking deleterious loss-of-function mutations give duplicate genes an immediate selective advantage and, together with effects of increased gene dosage, would predominantly determine the fates of the duplicate genes in the early phase of their evolution.

Download Full-text

Enhanced functional divergence of duplicate genes several million years after gene duplication in the Arabidopsis lineage

10.1101/047639 ◽

2016 ◽

Author(s):

Kousuke Hanada ◽

Ayumi Tezuka ◽

Masafumi Nozawa ◽

Yutaka Suzuki ◽

Sumio Sugano ◽

...

Keyword(s):

Gene Duplication ◽

Functional Divergence ◽

Purifying Selection ◽

Orthologous Gene ◽

Synonymous Substitution ◽

Duplicate Genes ◽

Duplicated Genes ◽

Highly Qualified ◽

Duplication Events ◽

Synonymous Substitution Rates

AbstractLineage-specifically duplicated genes likely contribute to the phenotypic divergence in closely related species. However, neither the frequency of duplication events nor the degree of selective pressures immediately after gene duplication is clear in the speciation process. Plants have substantially higher gene duplication rates than most other eukaryotes. Here, using Illumina short reads from Arabidopsis halleri, which has highly qualified plant genomes in close species (Brassica rapa, A. thaliana and A. lyrata), we succeeded in generating orthologous gene groups among B. rapa, A. thaliana, A. lyrata and A. halleri. The frequency of duplication events in the Arabidopsis lineage was approximately 10 times higher than the frequency inferred by comparative genomics of Arabidopsis, poplar, rice and moss. Of the currently retained genes in A. halleri, 11–24% had undergone gene duplication in the Arabidopsis lineage. To examine the degree of selective pressure for duplicated genes, we calculated the ratios of nonsynonymous to synonymous substitution rates (KA/KS) in the A. halleri-lyrata and A. halleri lineages. Using a maximum-likelihood framework, we examined positive (KA/KS > 1) and purifying selection (KA/KS < 1) at a significant level (P < 0.01). Duplicate genes tended to have a higher proportion of positive selection compared with non-duplicated genes. More interestingly, we found that functional divergence of duplicated genes was accelerated several million years after gene duplication at a higher proportion than immediately after gene duplication.

Download Full-text

Learning retention mechanisms and evolutionary parameters of duplicate genes from their expression data

10.1101/2020.06.19.162107 ◽

2020 ◽

Author(s):

Michael DeGiorgio ◽

Raquel Assis

Keyword(s):

Gene Expression ◽

Gene Duplication ◽

Statistical Learning ◽

Gene Evolution ◽

Functional Divergence ◽

Duplicate Gene ◽

Duplicate Genes ◽

Evolutionary Mechanisms ◽

Retention Mechanisms ◽

Gene Copies

AbstractLearning about the roles that duplicate genes play in the origins of novel phenotypes requires an understanding of how their functions evolve. To date, only one method—CDROM—has been developed with this goal in mind. In particular, CDROM employs gene expression distances as proxies for functional divergence, and then classifies the evolutionary mechanisms retaining duplicate genes from comparisons of these distances in a decision tree framework. However, CDROM does not account for stochastic shifts in gene expression or leverage advances in contemporary statistical learning for performing classification, nor is it capable of predicting the underlying parameters of duplicate gene evolution. Thus, here we develop CLOUD, a multi-layer neural network built upon a model of gene expression evolution that can both classify duplicate gene retention mechanisms and predict their underlying evolutionary parameters. We show that not only is the CLOUD classifier substantially more powerful and accurate than CDROM, but that it also yields accurate parameter predictions, enabling a better understanding of the specific forces driving the evolution and long-term retention of duplicate genes. Further, application of the CLOUD classifier and predictor to empirical data from Drosophila recapitulates many previous findings about gene duplication in this lineage, showing that new functions often emerge rapidly and asymmetrically in younger duplicate gene copies, and that functional divergence is driven by strong natural selection. Hence, CLOUD represents the best available method for classifying retention mechanisms and predicting evolutionary parameters of duplicate genes, thereby also highlighting the utility of incorporating sophisticated statistical learning techniques to address long-standing questions about evolution after gene duplication.

Download Full-text

Mutational and transcriptional landscape of spontaneous gene duplications and deletions in Caenorhabditis elegans

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1801930115 ◽

2018 ◽

Vol 115 (28) ◽

pp. 7386-7391 ◽

Cited By ~ 23

Author(s):

Anke Konrad ◽

Stephane Flibotte ◽

Jon Taylor ◽

Robert H. Waterston ◽

Donald G. Moerman ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Gene Duplication ◽

Gene Copy Number ◽

Purifying Selection ◽

Transcript Abundance ◽

Gene Copy ◽

Segmental Duplications ◽

Highly Expressed Genes ◽

New Gene ◽

Gene Duplicates

Gene duplication and deletion are pivotal processes shaping the structural and functional repertoire of genomes, with implications for disease, adaptation, and evolution. We employed a mutation accumulation (MA) framework partnered with high-throughput genomics to assess the molecular and transcriptional characteristics of newly arisen gene copy-number variants (CNVs) in Caenorhabditis elegans populations subjected to varying intensity of selection. Here, we report a direct spontaneous genome-wide rate of gene duplication of 2.9 × 10−5/gene per generation in C. elegans, the highest for any species to date. The rate of gene deletion is sixfold lower (5 × 10−6/gene per generation). Deletions of highly expressed genes are particularly deleterious, given their paucity in even the N = 1 lines with minimal efficacy of selection. The increase in average transcript abundance of new duplicates arising under minimal selection is significantly greater than twofold compared with single copies of the same gene, suggesting that genes in segmental duplications are frequently overactive at inception. The average increase in transcriptional activity of gene duplicates is greater in the N = 1 MA lines than in MA lines with larger population bottlenecks. There is an inverse relationship between the ancestral transcription levels of new gene duplicates and population size, with duplicate copies of highly expressed genes less likely to accumulate in larger populations. Our results demonstrate a fitness cost of increased transcription following duplication, which results in purifying selection against new gene duplicates. However, on average, duplications also provide a significant increase in gene expression that can facilitate adaptation to novel environmental challenges.

Download Full-text

The Probability of Preservation of a Newly Arisen Gene Duplicate

Genetics ◽

10.1093/genetics/159.4.1789 ◽

2001 ◽

Vol 159 (4) ◽

pp. 1789-1804 ◽

Cited By ~ 7

Author(s):

Michael Lynch ◽

Martin O'Hely ◽

Bruce Walsh ◽

Allan Force

Keyword(s):

Gene Duplication ◽

Duplicate Gene ◽

Selective Advantage ◽

Common Mechanism ◽

Active Selection ◽

Permanent Establishment ◽

Large Populations ◽

Genetic Mechanisms ◽

Differential Expansion ◽

Gene Duplicate

AbstractNewly emerging data from genome sequencing projects suggest that gene duplication, often accompanied by genetic map changes, is a common and ongoing feature of all genomes. This raises the possibility that differential expansion/contraction of various genomic sequences may be just as important a mechanism of phenotypic evolution as changes at the nucleotide level. However, the population-genetic mechanisms responsible for the success vs. failure of newly arisen gene duplicates are poorly understood. We examine the influence of various aspects of gene structure, mutation rates, degree of linkage, and population size (N) on the joint fate of a newly arisen duplicate gene and its ancestral locus. Unless there is active selection against duplicate genes, the probability of permanent establishment of such genes is usually no less than 1/(4N) (half of the neutral expectation), and it can be orders of magnitude greater if neofunctionalizing mutations are common. The probability of a map change (reassignment of a key function of an ancestral locus to a new chromosomal location) induced by a newly arisen duplicate is also generally >1/(4N) for unlinked duplicates, suggesting that recurrent gene duplication and alternative silencing may be a common mechanism for generating microchromosomal rearrangements responsible for postreproductive isolating barriers among species. Relative to subfunctionalization, neofunctionalization is expected to become a progressively more important mechanism of duplicate-gene preservation in populations with increasing size. However, even in large populations, the probability of neofunctionalization scales only with the square of the selective advantage. Tight linkage also influences the probability of duplicate-gene preservation, increasing the probability of subfunctionalization but decreasing the probability of neofunctionalization.

Download Full-text

Learning Retention Mechanisms and Evolutionary Parameters of Duplicate Genes from Their Expression Data

Molecular Biology and Evolution ◽

10.1093/molbev/msaa267 ◽

2020 ◽

Author(s):

Michael DeGiorgio ◽

Raquel Assis

Keyword(s):

Gene Expression ◽

Gene Duplication ◽

Statistical Learning ◽

Gene Evolution ◽

Functional Divergence ◽

Duplicate Gene ◽

Previous Method ◽

Duplicate Genes ◽

Evolutionary Mechanisms ◽

Retention Mechanisms

Abstract Learning about the roles that duplicate genes play in the origins of novel phenotypes requires an understanding of how their functions evolve. A previous method for achieving this goal, CDROM, employs gene expression distances as proxies for functional divergence and then classifies the evolutionary mechanisms retaining duplicate genes from comparisons of these distances in a decision tree framework. However, CDROM does not account for stochastic shifts in gene expression or leverage advances in contemporary statistical learning for performing classification, nor is it capable of predicting the parameters driving duplicate gene evolution. Thus, here we develop CLOUD, a multi-layer neural network built on a model of gene expression evolution that can both classify duplicate gene retention mechanisms and predict their underlying evolutionary parameters. We show that not only is the CLOUD classifier substantially more powerful and accurate than CDROM, but that it also yields accurate parameter predictions, enabling a better understanding of the specific forces driving the evolution and long-term retention of duplicate genes. Further, application of the CLOUD classifier and predictor to empirical data from Drosophila recapitulates many previous findings about gene duplication in this lineage, showing that new functions often emerge rapidly and asymmetrically in younger duplicate gene copies, and that functional divergence is driven by strong natural selection. Hence, CLOUD represents a major advancement in classifying retention mechanisms and predicting evolutionary parameters of duplicate genes, thereby highlighting the utility of incorporating sophisticated statistical learning techniques to address long-standing questions about evolution after gene duplication.

Download Full-text

DNA methylation signatures of duplicate gene evolution in angiosperms

10.1101/2020.08.31.275362 ◽

2020 ◽

Author(s):

Sunil K. Kenchanmane Raju ◽

S. Marshall Ledford ◽

Chad E. Niederhuth

Keyword(s):

Dna Methylation ◽

Gene Evolution ◽

Gene Dosage ◽

Single Gene ◽

Constitutive Expression ◽

Duplicate Gene ◽

Duplicate Genes ◽

Whole Genome ◽

Gene Duplicates ◽

Methylation Patterns

ABSTRACTGene duplications have greatly shaped the gene content of plants. Multiple factors, such as the epigenome, can shape the subsequent evolution of duplicate genes and are the subject of ongoing study. We analyze genic DNA methylation patterns in 43 angiosperm species and 928 Arabidopsis thaliana ecotypes to finding differences in the association of whole-genome and single-gene duplicates with genic DNA methylation patterns. Whole-genome duplicates were enriched for patterns associated with higher gene expression and depleted for patterns of non-CG DNA methylation associated with gene silencing. Single-gene duplicates showed variation in DNA methylation patterns based on modes of duplication (tandem, proximal, transposed, and dispersed) and species. Age of gene duplication was a key factor in the DNA methylation of single-gene duplicates. In single-gene duplicates, non-CG DNA methylation patterns associated with silencing were younger, less conserved, and enriched for presence-absence variation. In comparison, DNA methylation patterns associated with constitutive expression were older and more highly conserved. Surprisingly, across the phylogeny, genes marked by non-CG DNA methylation were enriched for duplicate pairs with evidence of positive selection. We propose that DNA methylation has a role in maintaining gene-dosage balance and silencing by non-CG methylation and may facilitate the evolutionary fate of duplicate genes.

Download Full-text

Genome-wide identification and evolutionary analysis of RLKs involved in the response to aluminium stress in peanut

BMC Plant Biology ◽

10.1186/s12870-021-03031-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xin Wang ◽

Ming-Hua Wu ◽

Dong Xiao ◽

Ruo-Lan Huang ◽

Jie Zhan ◽

...

Keyword(s):

Stress Responses ◽

Segmental Duplication ◽

Tandem Duplication ◽

Expression Patterns ◽

Purifying Selection ◽

Segmental Duplications ◽

Evolutionary Analysis ◽

Gene Pairs ◽

Al Stress ◽

Peanut Genome

Abstract Background As an important cash crop, the yield of peanut is influenced by soil acidification and pathogen infection. Receptor-like protein kinases play important roles in plant growth, development and stress responses. However, little is known about the number, location, structure, molecular phylogeny, and expression of RLKs in peanut, and no comprehensive analysis of RLKs in the Al stress response in peanuts have been reported. Results A total of 1311 AhRLKs were identified from the peanut genome. The AhLRR-RLKs and AhLecRLKs were further divided into 24 and 35 subfamilies, respectively. The AhRLKs were randomly distributed across all 20 chromosomes in the peanut. Among these AhRLKs, 9.53% and 61.78% originated from tandem duplications and segmental duplications, respectively. The ka/ks ratios of 96.97% (96/99) of tandem duplication gene pairs and 98.78% (646/654) of segmental duplication gene pairs were less than 1. Among the tested tandem duplication clusters, there were 28 gene conversion events. Moreover, all total of 90 Al-responsive AhRLKs were identified by mining transcriptome data, and they were divided into 7 groups. Most of the Al-responsive AhRLKs that clustered together had similar motifs and evolutionarily conserved structures. The gene expression patterns of these genes in different tissues were further analysed, and tissue-specifically expressed genes, including 14 root-specific Al-responsive AhRLKs were found. In addition, all 90 Al-responsive AhRLKs which were distributed unevenly in the subfamilies of AhRLKs, showed different expression patterns between the two peanut varieties (Al-sensitive and Al-tolerant) under Al stress. Conclusions In this study, we analysed the RLK gene family in the peanut genome. Segmental duplication events were the main driving force for AhRLK evolution, and most AhRLKs subject to purifying selection. A total of 90 genes were identified as Al-responsive AhRLKs, and the classification, conserved motifs, structures, tissue expression patterns and predicted functions of Al-responsive AhRLKs were further analysed and discussed, revealing their putative roles. This study provides a better understanding of the structures and functions of AhRLKs and Al-responsive AhRLKs.

Download Full-text

Systematic evidence from gene duplication and regulation

Australian Systematic Botany ◽

10.1071/sb9900145 ◽

1990 ◽

Vol 3 (1) ◽

pp. 145

Author(s):

DJ Colgan

Keyword(s):

Gene Duplication ◽

Evolutionary History ◽

Tandem Duplication ◽

Fragment Length Polymorphism ◽

Duplicate Genes ◽

Polymorphism Analysis ◽

Multiple Origins ◽

The Family ◽

History Of ◽

Phylogenetic Hypotheses

This paper is a review of the use of information regarding the presence of duplicate genes and their regulation in systematics. The review concentrates on data derived from protein electrophoresis and restriction fragment length polymorphism analysis. The appearance of a duplication in a subset of a group of species implies that the members of the subset belong to the same clade. Suppression of the duplication may render this clade apparently paraphyletic, but may itself be informative of relations within the lineage through patterns of loss of expression in all, or some tissues, or through restrictions of the formation of functional heteropolymers in polymeric enzymes. Examples are given of studies which have used such information to establish phylogenetic hypotheses at the family level, to identify an auto- or allo-polyploid origin of polyploid species and to determine whether there have been single or multiple origins of such species. The likelihood of homoplasy in the patterns of appearance and regulation of duplicates depends on the molecular basis of the duplication. In particular, the contrast between the expected consequences of tandem duplication and the expression of pseudogenes emphasises the value of determining the mechanism of the original duplication. Many instances of sporadic gene duplication are now known, and polyploidisation is a common event in the evolutionary history of both plants and animals. So the opportunities to discover duplicationrelated characters will arise in many systematic studies. A program is presented to increase the chances that such useful information will be recognisable during the studies.

Download Full-text

Host Insect Inhibitor-of-Apoptosis SfIAP Functionally Replaces Baculovirus IAP but Is Differentially Regulated by Its N-Terminal Leader

Journal of Virology ◽

10.1128/jvi.01311-10 ◽

2010 ◽

Vol 84 (21) ◽

pp. 11448-11460 ◽

Cited By ~ 20

Author(s):

Rebecca J. Cerio ◽

Rianna Vandergaast ◽

Paul D. Friesen

Keyword(s):

Selective Advantage ◽

Biochemical Properties ◽

Inhibitor Of Apoptosis ◽

Loss Of Function ◽

Wild Type ◽

Host Insect ◽

Orgyia Pseudotsugata ◽

Induced Apoptosis ◽

Lepidopteran Host ◽

Maximal Stability

ABSTRACT The inhibitor-of-apoptosis (IAP) proteins encoded by baculoviruses bear a striking resemblance to the cellular IAP homologs of their invertebrate hosts. By virtue of the acquired selective advantage of blocking virus-induced apoptosis, baculoviruses may have captured cellular IAP genes that subsequently evolved for virus-specific objectives. To compare viral and host IAPs, we defined antiapoptotic properties of SfIAP, the principal cellular IAP of the lepidopteran host Spodoptera frugiperda. We report here that SfIAP prevented virus-induced apoptosis as well as viral Op-IAP3 (which is encoded by the Orgyia pseudotsugata nucleopolyhedrovirus) when overexpressed from the baculovirus genome. Like Op-IAP3, SfIAP blocked apoptosis at a step prior to caspase activation. Both of the baculovirus IAP repeats (BIRs) were required for SfIAP function. Moreover, deletion of the C-terminal RING motif generated a loss-of-function SfIAP that interacted and dominantly interfered with wild-type SfIAP. Like Op-IAP3, wild-type SfIAP formed intracellular homodimers, suggesting that oligomerization is a functional requirement for both cellular and viral IAPs. SfIAP possesses a ∼100-residue N-terminal leader domain, which is absent among all viral IAPs. Remarkably, deletion of the leader yielded a fully functional SfIAP with dramatically increased protein stability. Thus, the SfIAP leader contains an instability motif that may confer regulatory options for cellular IAPs that baculovirus IAPs have evolved to bypass for maximal stability and antiapoptotic potency. Our findings that SfIAP and viral IAPs have common motifs, share multiple biochemical properties including oligomerization, and act at the same step to block apoptosis support the hypothesis that baculoviral IAPs were derived by acquisition of host insect IAPs.

Download Full-text

Knockdown of duplicated zebrafishhoxb1genes reveals distinct roles in hindbrain patterning and a novel mechanism of duplicate gene retention

Development ◽

10.1242/dev.129.10.2339 ◽

2002 ◽

Vol 129 (10) ◽

pp. 2339-2354 ◽

Cited By ~ 6

Author(s):

James M. McClintock ◽

Mazen A. Kheirbek ◽

Victoria E. Prince

Keyword(s):

Protein Function ◽

Cranial Nerve ◽

Duplicate Gene ◽

Regulatory Elements ◽

Duplicate Genes ◽

Duplicated Genes ◽

Gene Retention ◽

Redundant Functions ◽

Group 1 ◽

Rhombomere 4

We have used a morpholino-based knockdown approach to investigate the functions of a pair of zebrafish Hox gene duplicates, hoxb1a and hoxb1b, which are expressed during development of the hindbrain. We find that the zebrafish hoxb1 duplicates have equivalent functions to mouse Hoxb1 and its paralogue Hoxa1. Thus, we have revealed a ‘function shuffling’ among genes of paralogue group 1 during the evolution of vertebrates. Like mouse Hoxb1, zebrafish hoxb1a is required for migration of the VIIth cranial nerve branchiomotor neurons from their point of origin in hindbrain rhombomere 4 towards the posterior. By contrast, zebrafish hoxb1b, like mouse Hoxa1, is required for proper segmental organization of rhombomere 4 and the posterior hindbrain. Double knockdown experiments demonstrate that the zebrafish hoxb1 duplicates have partially redundant functions. However, using an RNA rescue approach, we reveal that these duplicated genes do not have interchangeable biochemical functions: only hoxb1a can properly pattern the VIIth cranial nerve. Despite this difference in protein function, we provide evidence that the hoxb1 duplicate genes were initially maintained in the genome because of complementary degenerative mutations in defined cis-regulatory elements.

Download Full-text