Editorial

4 pages, 200 KiB

Open AccessEditorial

Evolutionary New Genes in a Growing Paradigm

by Esther Betrán and Manyuan Long

Genes 2022, 13(9), 1605; https://doi.org/10.3390/genes13091605 - 08 Sep 2022

Cited by 2 | Viewed by 1387

How new genes evolve has become an interesting problem in biology, particularly in evolutionary biology [...] Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

Research

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19 pages, 3252 KiB

Open AccessArticle

Retrogene Duplication and Expression Patterns Shaped by the Evolution of Sex Chromosomes in Malaria Mosquitoes

by Duncan Miller, Jianhai Chen, Jiangtao Liang, Esther Betrán, Manyuan Long and Igor V. Sharakhov

Genes 2022, 13(6), 968; https://doi.org/10.3390/genes13060968 - 28 May 2022

Cited by 6 | Viewed by 2430

Abstract

Genes that originate during evolution are an important source of novel biological functions. Retrogenes are functional copies of genes produced by retroduplication and as such are located in different genomic positions. To investigate retroposition patterns and retrogene expression, we computationally identified interchromosomal retroduplication [...] Read more.

Genes that originate during evolution are an important source of novel biological functions. Retrogenes are functional copies of genes produced by retroduplication and as such are located in different genomic positions. To investigate retroposition patterns and retrogene expression, we computationally identified interchromosomal retroduplication events in nine portions of the phylogenetic history of malaria mosquitoes, making use of species that do or do not have classical sex chromosomes to test the roles of sex-linkage. We found 40 interchromosomal events and a significant excess of retroduplications from the X chromosome to autosomes among a set of young retrogenes. These young retroposition events occurred within the last 100 million years in lineages where all species possessed differentiated sex chromosomes. An analysis of available microarray and RNA-seq expression data for Anopheles gambiae showed that many of the young retrogenes evolved male-biased expression in the reproductive organs. Young autosomal retrogenes with increased meiotic or postmeiotic expression in the testes tend to be male biased. In contrast, older retrogenes, i.e., in lineages with undifferentiated sex chromosomes, do not show this particular chromosomal bias and are enriched for female-biased expression in reproductive organs. Our reverse-transcription PCR data indicates that most of the youngest retrogenes, which originated within the last 47.6 million years in the subgenus Cellia, evolved non-uniform expression patterns across body parts in the males and females of An. coluzzii. Finally, gene annotation revealed that mitochondrial function is a prominent feature of the young autosomal retrogenes. We conclude that mRNA-mediated gene duplication has produced a set of genes that contribute to mosquito reproductive functions and that different biases are revealed after the sex chromosomes evolve. Overall, these results suggest potential roles for the evolution of meiotic sex chromosome inactivation in males and of sexually antagonistic conflict related to mitochondrial energy function as the main selective pressures for X-to-autosome gene reduplication and testis-biased expression in these mosquito lineages. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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16 pages, 3318 KiB

Open AccessArticle

COX4-like, a Nuclear-Encoded Mitochondrial Gene Duplicate, Is Essential for Male Fertility in Drosophila melanogaster

by Mohammadmehdi Eslamieh, Ayda Mirsalehi, Dragomira N. Markova and Esther Betrán

Genes 2022, 13(3), 424; https://doi.org/10.3390/genes13030424 - 25 Feb 2022

Cited by 6 | Viewed by 2535

Abstract

Recent studies on nuclear-encoded mitochondrial genes (N-mt genes) in Drosophila melanogaster have shown a unique pattern of expression for newly duplicated N-mt genes, with many duplicates having a testis-biased expression and playing an essential role in spermatogenesis. In this study, we investigated a [...] Read more.

Recent studies on nuclear-encoded mitochondrial genes (N-mt genes) in Drosophila melanogaster have shown a unique pattern of expression for newly duplicated N-mt genes, with many duplicates having a testis-biased expression and playing an essential role in spermatogenesis. In this study, we investigated a newly duplicated N-mt gene—i.e., Cytochrome c oxidase 4-like (COX4L)—in order to understand its function and, consequently, the reason behind its retention in the D. melanogaster genome. The COX4L gene is a duplicate of the Cytochrome c oxidase 4 (COX4) gene of OXPHOS complex IV. While the parental COX4 gene has been found in all eukaryotes, including single-cell eukaryotes such as yeast, we show that COX4L is only present in the Brachycera suborder of Diptera; thus, both genes are present in all Drosophila species, but have significantly different patterns of expression: COX4 is highly expressed in all tissues, while COX4L has a testis-specific expression. To understand the function of this new gene, we first knocked down its expression in the D. melanogaster germline using two different RNAi lines driven by the bam-Gal4 driver; second, we created a knockout strain for this gene using CRISPR-Cas9 technology. Our results showed that knockdown and knockout lines of COX4L produce partial sterility and complete sterility in males, respectively, where a lack of sperm individualization was observed in both cases. Male infertility was prevented by driving COX4L-HA in the germline, but not when driving COX4-HA. In addition, ectopic expression of COX4L in the soma caused embryonic lethality, while overexpression in the germline led to a reduction in male fertility. COX4L-KO mitochondria show reduced membrane potential, providing a plausible explanation for the male sterility observed in these flies. This prominent loss-of-function phenotype, along with its testis-biased expression and its presence in the Drosophila sperm proteome, suggests that COX4L is a paralogous, specialized gene that is assembled in OXPHOS complex IV of male germline cells and/or sperm mitochondria. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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24 pages, 4582 KiB

Open AccessArticle

New Genomic Signals Underlying the Emergence of Human Proto-Genes

by Anna Grandchamp, Katrin Berk, Elias Dohmen and Erich Bornberg-Bauer

Genes 2022, 13(2), 284; https://doi.org/10.3390/genes13020284 - 31 Jan 2022

Cited by 7 | Viewed by 3326

Abstract

De novo genes are novel genes which emerge from non-coding DNA. Until now, little is known about de novo genes’ properties, correlated to their age and mechanisms of emergence. In this study, we investigate four related properties: introns, upstream regulatory motifs, 5′ Untranslated [...] Read more.

De novo genes are novel genes which emerge from non-coding DNA. Until now, little is known about de novo genes’ properties, correlated to their age and mechanisms of emergence. In this study, we investigate four related properties: introns, upstream regulatory motifs, 5′ Untranslated regions (UTRs) and protein domains, in 23,135 human proto-genes. We found that proto-genes contain introns, whose number and position correlates with the genomic position of proto-gene emergence. The origin of these introns is debated, as our results suggest that 41% of proto-genes might have captured existing introns, and 13.7% of them do not splice the ORF. We show that proto-genes which emerged via overprinting tend to be more enriched in core promotor motifs, while intergenic and intronic genes are more enriched in enhancers, even if the TATA motif is most commonly found upstream in these genes. Intergenic and intronic 5′ UTRs of proto-genes have a lower potential to stabilise mRNA structures than exonic proto-genes and established human genes. Finally, we confirm that proteins expressed by proto-genes gain new putative domains with age. Overall, we find that regulatory motifs inducing transcription and translation of previously non-coding sequences may facilitate proto-gene emergence. Our study demonstrates that introns, 5′ UTRs, and domains have specific properties in proto-genes. We also emphasize that the genomic positions of de novo genes strongly impacts these properties. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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20 pages, 1865 KiB

Open AccessArticle

Rapid Cis–Trans Coevolution Driven by a Novel Gene Retroposed from a Eukaryotic Conserved CCR4–NOT Component in Drosophila

by Benjamin H. Krinsky, Robert K. Arthur, Shengqian Xia, Dylan Sosa, Deanna Arsala, Kevin P. White and Manyuan Long

Genes 2022, 13(1), 57; https://doi.org/10.3390/genes13010057 - 26 Dec 2021

Cited by 1 | Viewed by 3413

Abstract

Young, or newly evolved, genes arise ubiquitously across the tree of life, and they can rapidly acquire novel functions that influence a diverse array of biological processes. Previous work identified a young regulatory duplicate gene in Drosophila, Zeus that unexpectedly diverged rapidly [...] Read more.

Young, or newly evolved, genes arise ubiquitously across the tree of life, and they can rapidly acquire novel functions that influence a diverse array of biological processes. Previous work identified a young regulatory duplicate gene in Drosophila, Zeus that unexpectedly diverged rapidly from its parent, Caf40, an extremely conserved component in the CCR4–NOT machinery in post-transcriptional and post-translational regulation of eukaryotic cells, and took on roles in the male reproductive system. This neofunctionalization was accompanied by differential binding of the Zeus protein to loci throughout the Drosophila melanogaster genome. However, the way in which new DNA-binding proteins acquire and coevolve with their targets in the genome is not understood. Here, by comparing Zeus ChIP-Seq data from D. melanogaster and D. simulans to the ancestral Caf40 binding events from D. yakuba, a species that diverged before the duplication event, we found a dynamic pattern in which Zeus binding rapidly coevolved with a previously unknown DNA motif, which we term Caf40 and Zeus-Associated Motif (CAZAM), under the influence of positive selection. Interestingly, while both copies of Zeus acquired targets at male-biased and testis-specific genes, D. melanogaster and D. simulans proteins have specialized binding on different chromosomes, a pattern echoed in the evolution of the associated motif. Using CRISPR-Cas9-mediated gene knockout of Zeus and RNA-Seq, we found that Zeus regulated the expression of 661 differentially expressed genes (DEGs). Our results suggest that the evolution of young regulatory genes can be coupled to substantial rewiring of the transcriptional networks into which they integrate, even over short evolutionary timescales. Our results thus uncover dynamic genome-wide evolutionary processes associated with new genes. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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15 pages, 2127 KiB

Open AccessArticle

Effects of the Expression of Random Sequence Clones on Growth and Transcriptome Regulation in Escherichia coli

by Devika Bhave and Diethard Tautz

Genes 2022, 13(1), 53; https://doi.org/10.3390/genes13010053 - 24 Dec 2021

Cited by 9 | Viewed by 2582

Abstract

Comparative genomic analyses have provided evidence that new genetic functions can emerge out of random nucleotide sequences. Here, we apply a direct experimental approach to study the effects of plasmids harboring random sequence inserts under the control of an inducible promoter. Based on [...] Read more.

Comparative genomic analyses have provided evidence that new genetic functions can emerge out of random nucleotide sequences. Here, we apply a direct experimental approach to study the effects of plasmids harboring random sequence inserts under the control of an inducible promoter. Based on data from previously described experiments dealing with the growth of clones within whole libraries, we extracted specific clones that had shown either negative, neutral or positive effects on relative cell growth. We analyzed these individually with respect to growth characteristics and the impact on the transcriptome. We find that candidate clones for negative peptides lead to growth arrest by eliciting a general stress response. Overexpression of positive clones, on the other hand, does not change the exponential growth rates of hosts, and they show a growth advantage over a neutral clone when tested in direct competition experiments. Transcriptomic changes in positive clones are relatively moderate and specific to each clone. We conclude from our experiments that random sequence peptides are indeed a suitable source for the de novo evolution of genetic functions. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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18 pages, 2083 KiB

Open AccessArticle

The Effects of Sequence Length and Composition of Random Sequence Peptides on the Growth of E. coli Cells

by Johana F. Castro and Diethard Tautz

Genes 2021, 12(12), 1913; https://doi.org/10.3390/genes12121913 - 28 Nov 2021

Cited by 9 | Viewed by 2097

Abstract

We study the potential for the de novo evolution of genes from random nucleotide sequences using libraries of E. coli expressing random sequence peptides. We assess the effects of such peptides on cell growth by monitoring frequency changes in individual clones in a [...] Read more.

We study the potential for the de novo evolution of genes from random nucleotide sequences using libraries of E. coli expressing random sequence peptides. We assess the effects of such peptides on cell growth by monitoring frequency changes in individual clones in a complex library through four serial passages. Using a new analysis pipeline that allows the tracing of peptides of all lengths, we find that over half of the peptides have consistent effects on cell growth. Across nine different experiments, around 16% of clones increase in frequency and 36% decrease, with some variation between individual experiments. Shorter peptides (8–20 residues), are more likely to increase in frequency, longer ones are more likely to decrease. GC content, amino acid composition, intrinsic disorder, and aggregation propensity show slightly different patterns between peptide groups. Sequences that increase in frequency tend to be more disordered with lower aggregation propensity. This coincides with the observation that young genes with more disordered structures are better tolerated in genomes. Our data indicate that random sequences can be a source of evolutionary innovation, since a large fraction of them are well tolerated by the cells or can provide a growth advantage. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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15 pages, 3826 KiB

Open AccessArticle

Evolutionary Characterization of the Short Protein SPAAR

by Jiwon Lee, Aaron Wacholder and Anne-Ruxandra Carvunis

Genes 2021, 12(12), 1864; https://doi.org/10.3390/genes12121864 - 24 Nov 2021

Cited by 2 | Viewed by 1860

Abstract

Microproteins (<100 amino acids) are receiving increasing recognition as important participants in numerous biological processes, but their evolutionary dynamics are poorly understood. SPAAR is a recently discovered microprotein that regulates muscle regeneration and angiogenesis through interactions with conserved signaling pathways. Interestingly, SPAAR does [...] Read more.

Microproteins (<100 amino acids) are receiving increasing recognition as important participants in numerous biological processes, but their evolutionary dynamics are poorly understood. SPAAR is a recently discovered microprotein that regulates muscle regeneration and angiogenesis through interactions with conserved signaling pathways. Interestingly, SPAAR does not belong to any known protein family and has known homologs exclusively among placental mammals. This lack of distant homology could be caused by challenges in homology detection of short sequences, or it could indicate a recent de novo emergence from a noncoding sequence. By integrating syntenic alignments and homology searches, we identify SPAAR orthologs in marsupials and monotremes, establishing that SPAAR has existed at least since the emergence of mammals. SPAAR shows substantial primary sequence divergence but retains a conserved protein structure. In primates, we infer two independent evolutionary events leading to the de novo origination of 5′ elongated isoforms of SPAAR from a noncoding sequence and find evidence of adaptive evolution in this extended region. Thus, SPAAR may be of ancient origin, but it appears to be experiencing continual evolutionary innovation in mammals. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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11 pages, 1023 KiB

Open AccessFeature PaperArticle

Pattern of New Gene Origination in a Special Fish Lineage, the Flatfishes

by Haorong Li, Chunyan Chen, Zhongkai Wang, Kun Wang, Yongxin Li and Wen Wang

Genes 2021, 12(11), 1819; https://doi.org/10.3390/genes12111819 - 19 Nov 2021

Cited by 3 | Viewed by 1921

Abstract

Origination of new genes are of inherent interest of evolutionary geneticists for decades, but few studies have addressed the general pattern in a fish lineage. Using our recent released whole genome data of flatfishes, which evolved one of the most specialized body plans [...] Read more.

Origination of new genes are of inherent interest of evolutionary geneticists for decades, but few studies have addressed the general pattern in a fish lineage. Using our recent released whole genome data of flatfishes, which evolved one of the most specialized body plans in vertebrates, we identified 1541 (6.9% of the starry flounder genes) flatfish-lineage-specific genes. The origination pattern of these flatfish new genes is largely similar to those observed in other vertebrates, as shown by the proportion of DNA-mediated duplication (1317; 85.5%), RNA-mediated duplication (retrogenes; 96; 6.2%), and de novo–origination (128; 8.3%). The emergence rate of species-specific genes is 32.1 per Mya and the whole average level rate for the flatfish-lineage-specific genes is 20.9 per Mya. A large proportion (31.4%) of these new genes have been subjected to selection, in contrast to the 4.0% in primates, while the old genes remain quite similar (66.4% vs. 65.0%). In addition, most of these new genes (70.8%) are found to be expressed, indicating their functionality. This study not only presents one example of systematic new gene identification in a teleost taxon based on comprehensive phylogenomic data, but also shows that new genes may play roles in body planning. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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19 pages, 2017 KiB

Open AccessFeature PaperArticle

New Genes in the Drosophila Y Chromosome: Lessons from D. willistoni

by João Ricchio, Fabiana Uno and A. Bernardo Carvalho

Genes 2021, 12(11), 1815; https://doi.org/10.3390/genes12111815 - 18 Nov 2021

Cited by 2 | Viewed by 2360

Abstract

Y chromosomes play important roles in sex determination and male fertility. In several groups (e.g., mammals) there is strong evidence that they evolved through gene loss from a common X-Y ancestor, but in Drosophila the acquisition of new genes plays a major role. [...] Read more.

Y chromosomes play important roles in sex determination and male fertility. In several groups (e.g., mammals) there is strong evidence that they evolved through gene loss from a common X-Y ancestor, but in Drosophila the acquisition of new genes plays a major role. This conclusion came mostly from studies in two species. Here we report the identification of the 22 Y-linked genes in D. willistoni. They all fit the previously observed pattern of autosomal or X-linked testis-specific genes that duplicated to the Y. The ratio of gene gains to gene losses is ~25 in D. willistoni, confirming the prominent role of gene gains in the evolution of Drosophila Y chromosomes. We also found four large segmental duplications (ranging from 62 kb to 303 kb) from autosomal regions to the Y, containing ~58 genes. All but four of these duplicated genes became pseudogenes in the Y or disappeared. In the GK20609 gene the Y-linked copy remained functional, whereas its original autosomal copy degenerated, demonstrating how autosomal genes are transferred to the Y chromosome. Since the segmental duplication that carried GK20609 contained six other testis-specific genes, it seems that chance plays a significant role in the acquisition of new genes by the Drosophila Y chromosome. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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15 pages, 2563 KiB

Open AccessArticle

On the Origin and Evolution of Drosophila New Genes during Spermatogenesis

by Qianwei Su, Huangyi He and Qi Zhou

Genes 2021, 12(11), 1796; https://doi.org/10.3390/genes12111796 - 15 Nov 2021

Cited by 8 | Viewed by 2809

Abstract

The origin of functional new genes is a basic biological process that has significant contribution to organismal diversity. Previous studies in both Drosophila and mammals showed that new genes tend to be expressed in testes and avoid the X chromosome, presumably because of [...] Read more.

The origin of functional new genes is a basic biological process that has significant contribution to organismal diversity. Previous studies in both Drosophila and mammals showed that new genes tend to be expressed in testes and avoid the X chromosome, presumably because of meiotic sex chromosome inactivation (MSCI). Here, we analyze the published single-cell transcriptome data of Drosophila adult testis and find an enrichment of male germline mitotic genes, but an underrepresentation of meiotic genes on the X chromosome. This can be attributed to an excess of autosomal meiotic genes that were derived from their X-linked mitotic progenitors, which provides direct cell-level evidence for MSCI in Drosophila. We reveal that new genes, particularly those produced by retrotransposition, tend to exhibit an expression shift toward late spermatogenesis compared with their parental copies, probably due to the more intensive sperm competition or sexual conflict. Our results dissect the complex factors including age, the origination mechanisms and the chromosomal locations that influence the new gene origination and evolution in testes, and identify new gene cases that show divergent cell-level expression patterns from their progenitors for future functional studies. Full article

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17 pages, 2234 KiB

Open AccessArticle

Propagation of a De Novo Gene under Natural Selection: Antifreeze Glycoprotein Genes and Their Evolutionary History in Codfishes

by Xuan Zhuang and C.-H. Christina Cheng

Genes 2021, 12(11), 1777; https://doi.org/10.3390/genes12111777 - 09 Nov 2021

Cited by 5 | Viewed by 2461

Abstract

The de novo birth of functional genes from non-coding DNA as an important contributor to new gene formation is increasingly supported by evidence from diverse eukaryotic lineages. However, many uncertainties remain, including how the incipient de novo genes would continue to evolve and [...] Read more.

The de novo birth of functional genes from non-coding DNA as an important contributor to new gene formation is increasingly supported by evidence from diverse eukaryotic lineages. However, many uncertainties remain, including how the incipient de novo genes would continue to evolve and the molecular mechanisms underlying their evolutionary trajectory. Here we address these questions by investigating evolutionary history of the de novo antifreeze glycoprotein (AFGP) gene and gene family in gadid (codfish) lineages. We examined AFGP phenotype on a phylogenetic framework encompassing a broad sampling of gadids from freezing and non-freezing habitats. In three select species representing different AFGP-bearing clades, we analyzed all AFGP gene family members and the broader scale AFGP genomic regions in detail. Codon usage analyses suggest that motif duplication produced the intragenic AFGP tripeptide coding repeats, and rapid sequence divergence post-duplication stabilized the recombination-prone long repetitive coding region. Genomic loci analyses support AFGP originated once from a single ancestral genomic origin, and shed light on how the de novo gene proliferated into a gene family. Results also show the processes of gene duplication and gene loss are distinctive in separate clades, and both genotype and phenotype are commensurate with differential local selective pressures. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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13 pages, 1032 KiB

Open AccessArticle

Lineage-Specific Genes and Family Expansions in Dictyostelid Genomes Display Expression Bias and Evolutionary Diversification during Development

by Saara K. Luna and Frédéric J. J. Chain

Genes 2021, 12(10), 1628; https://doi.org/10.3390/genes12101628 - 16 Oct 2021

Cited by 7 | Viewed by 2967

Abstract

Gene duplications generate new genes that can contribute to expression changes and the evolution of new functions. Genomes often consist of gene families that undergo expansions, some of which occur in specific lineages that reflect recent adaptive diversification. In this study, lineage-specific genes [...] Read more.

Gene duplications generate new genes that can contribute to expression changes and the evolution of new functions. Genomes often consist of gene families that undergo expansions, some of which occur in specific lineages that reflect recent adaptive diversification. In this study, lineage-specific genes and gene family expansions were studied across five dictyostelid species to determine when and how they are expressed during multicellular development. Lineage-specific genes were found to be enriched among genes with biased expression (predominant expression in one developmental stage) in each species and at most developmental time points, suggesting independent functional innovations of new genes throughout the phylogeny. Biased duplicate genes had greater expression divergence than their orthologs and paralogs, consistent with subfunctionalization or neofunctionalization. Lineage-specific expansions in particular had biased genes with both molecular signals of positive selection and high expression, suggesting adaptive genetic and transcriptional diversification following duplication. Our results present insights into the potential contributions of lineage-specific genes and families in generating species-specific phenotypes during multicellular development in dictyostelids. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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Review

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20 pages, 465 KiB

Open AccessReview

Gene Duplication and Gene Fusion Are Important Drivers of Tumourigenesis during Cancer Evolution

by Cian Glenfield and Hideki Innan

Genes 2021, 12(9), 1376; https://doi.org/10.3390/genes12091376 - 31 Aug 2021

Cited by 17 | Viewed by 6283

Abstract

Chromosomal rearrangement and genome instability are common features of cancer cells in human. Consequently, gene duplication and gene fusion events are frequently observed in human malignancies and many of the products of these events are pathogenic, representing significant drivers of tumourigenesis and cancer [...] Read more.

Chromosomal rearrangement and genome instability are common features of cancer cells in human. Consequently, gene duplication and gene fusion events are frequently observed in human malignancies and many of the products of these events are pathogenic, representing significant drivers of tumourigenesis and cancer evolution. In certain subsets of cancers duplicated and fused genes appear to be essential for initiation of tumour formation, and some even have the capability of transforming normal cells, highlighting the importance of understanding the events that result in their formation. The mechanisms that drive gene duplication and fusion are unregulated in cancer and they facilitate rapid evolution by selective forces akin to Darwinian survival of the fittest on a cellular level. In this review, we examine current knowledge of the landscape and prevalence of gene duplication and gene fusion in human cancers. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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Other

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13 pages, 1557 KiB

Open AccessBrief Report

Functional Innovation through Gene Duplication Followed by Frameshift Mutation

by Baocheng Guo, Ming Zou, Takahiro Sakamoto and Hideki Innan

Genes 2022, 13(2), 190; https://doi.org/10.3390/genes13020190 - 21 Jan 2022

Cited by 1 | Viewed by 3631

Abstract

In his influential book “Evolution by Gene Duplication”, Ohno postulated that frameshift mutation could lead to a new function after duplication, but frameshift mutation is generally thought to be deleterious, and thus drew little attention in functional innovation in duplicate evolution. [...] Read more.

In his influential book “Evolution by Gene Duplication”, Ohno postulated that frameshift mutation could lead to a new function after duplication, but frameshift mutation is generally thought to be deleterious, and thus drew little attention in functional innovation in duplicate evolution. To this end, we here report an exhaustive survey of the genomes of human, mouse, zebrafish, and fruit fly. We identified 80 duplicate genes that involved frameshift mutations after duplication. The frameshift mutation preferentially located close to the C-terminus in most cases (55/88), which indicated that a frameshift mutation that changed the reading frame in a small part at the end of a duplicate may likely have contributed to adaptive evolution (e.g., human genes NOTCH2NL and ARHGAP11B) otherwise too deleterious to survive. A few cases (11/80) involved multiple frameshift mutations, exhibiting various patterns of modifications of the reading frame. Functionality of duplicate genes involving frameshift mutations was confirmed by sequence characteristics and expression profile, suggesting a potential role of frameshift mutation in creating functional novelty. We thus showed that genomes have non-negligible numbers of genes that have experienced frameshift mutations following gene duplication. Our results demonstrated the potential importance of frameshift mutations in molecular evolution, as Ohno verbally argued 50 years ago. Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

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