Parallel evolution of chimeric fusion genes

Jones, Corbin D.; Begun, David J.

doi:10.1073/pnas.0503528102

Cited by 64 publications

(59 citation statements)

References 40 publications

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“…3; Table 1) suggests that the positive selection was episodic: it occurred in the primate ancestor and was followed by nearly neutral evolution after speciation. While this is the first example of positive selection on a retrogene that arose from an intergenically spliced transcript, our data are consistent with the burst of adaptive evolution after gene duplication, previously observed in primates and Drosophila (Zhang et al 1998;Jones and Begun 2005).…”

Section: Resultssupporting

confidence: 78%

A novel testis ubiquitin-binding protein gene arose by exon shuffling in hominoids

et al. 2007

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Most new genes arise by duplication of existing gene structures, after which relaxed selection on the new copy frequently leads to mutational inactivation of the duplicate; only rarely will a new gene with modified function emerge. Here we describe a unique mechanism of gene creation, whereby new combinations of functional domains are assembled at the RNA level from distinct genes, and the resulting chimera is then reverse transcribed and integrated into the genome by the L1 retrotransposon. We characterized a novel gene, which we termed PIP5K1A and PSMD4-like (PIPSL), created by this mechanism from an intergenic transcript between the phosphatidylinositol-4-phosphate 5-kinase (PIP5K1A) and the 26S proteasome subunit (PSMD4) genes in a hominoid ancestor. PIPSL is transcribed specifically in the testis both in humans and chimpanzees, and is post-transcriptionally repressed by independent mechanisms in these primate lineages. The PIPSL gene encodes a chimeric protein combining the lipid kinase domain of PIP5K1A and the ubiquitin-binding motifs of PSMD4. Strong positive selection on PIPSL led to its rapid divergence from the parental genes PIP5K1A and PSMD4, forming a chimeric protein with a distinct cellular localization and minimal lipid kinase activity, but significant affinity for cellular ubiquitinated proteins. PIPSL is a tightly regulated, testis-specific novel ubiquitin-binding protein formed by an unusual exon-shuffling mechanism in hominoid primates and represents a key example of rapid evolution of a testis-specific gene.[Supplemental material is available online at www.genome.org.]Sequence comparisons of completed genomes (Waterston et al. 2002;Gibbs et al. 2004;Mikkelsen et al. 2005) have revealed that de novo emergence of novel genes is rare. The majority of new genes arise by inadvertent plagiarism of existing genomic structures, most often by duplication and subsequent divergence of whole genes or gene modules (Ohno 1970;Long et al. 2003). These duplications often occur as part of larger segmental duplications (Samonte and Eichler 2002), but intronless copies of individual genes can also be disseminated throughout genomes by the activity of the LINE-1 (L1) retrotransposon ). In the presence of the original prototype gene, faithfully duplicated whole genes are rapidly inactivated by mutations as selective pressures are relaxed; only a rare replica will survive to acquire a novel function (Kimura 1983;Samonte and Eichler 2002). In contrast, while acquisition of novel functional domains (typically as alternative exons or products of intergenic recombination) allows rapid and creative functional adaptations, it also carries a barrier to fixation, as modifications to the original gene may have a negative impact on its function and host fitness. Here, we describe another mechanism of gene creation, whereby new combinations of functional domains are assembled on the RNA level, and the resulting chimera is then introduced into the genome by L1 reverse transcriptase. We characterized a novel gene, which we c...

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Section: Resultssupporting

confidence: 78%

A novel testis ubiquitin-binding protein gene arose by exon shuffling in hominoids

et al. 2007

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“…As expected on the basis of analysis of recently evolved genes Jones and Begun 2005) and genes that are enriched for testis expression (Prö schel et al 2006), the d N /d S ratios for these genes (Table 2) (Table 1), in spite of the fact that it has a history of directional selection in the sibling species. This finding, which mirrors results from melanogaster subgroup Acps (Begun and Lindfors 2005), supports the idea that functional roles of reproduction-related genes and the modes of selection impinging on them may change over relatively short time scales.…”

Section: Resultsmentioning

confidence: 92%

“…A long history of genomic investigation supports the importance of novelties deriving from duplication of pre-existing genes or parts thereof. For example, exon duplication, gene duplication (including via retrotransposition), and gene fusions contribute to new genes in many lineages (Ohno 1970;Li 1997), including Drosophila (Long and Langley 1993;Nurminsky et al 1998;Betran et al 2002;Long et al 2003;Wang et al 2004;Jones and Begun 2005;Loppin et al 2005).…”

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confidence: 99%

Evidence forde NovoEvolution of Testis-Expressed Genes in theDrosophila yakuba/Drosophila erectaClade

et al. 2007

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The mutational origin and subsequent evolution of de novo genes, which are hypothesized to be genes of recent origin that are not obviously related to ancestral coding sequence, are poorly understood. However, accumulating evidence suggests that such genes may often function in male reproduction. Here we use testis-derived expressed sequence tags (ESTs) from Drosophila yakuba to identify genes that have likely arisen either in D. yakuba or in the D. yakuba/D. erecta ancestor. We found several such genes, which show testis-biased expression and are often X-linked. Comparative data indicate that three of these genes have very short open reading frames, which suggests the possibility that a significant number of testis-biased de novo genes in the D. yakuba/D. erecta clade may be noncoding RNA genes. These data, along with previously published data from D. melanogaster, support the idea that many de novo Drosophila genes function in male reproduction and that a small region of the X chromosome in the melanogaster subgroup may be a hotspot for the evolution of novel testis-biased genes.T HE availability of genome sequences, particularly those from closely related species, allows for systematic investigation into the origin and evolution of novel genes. Although difficult to rigorously define, here we use the term to refer to recently evolved (i.e., speciesspecific or clade-specific) genes, which likely have major modifications of or wholesale departures from ancestral function. Well-annotated genomes provide the best substrate for identifying novel genes, as detailed enumeration of bona fide functional elements provides a starting point for genomic identification of related elements with recent origins. A long history of genomic investigation supports the importance of novelties deriving from duplication of pre-existing genes or parts thereof. For example, exon duplication, gene duplication (including via retrotransposition), and gene fusions contribute to new genes in many lineages (Ohno 1970;Li 1997) While the origin of new genes by duplication of preexisting coding sequence is clearly established as an important component of genome evolution, the question of novel genetic functions that do not clearly derive from closely related genes has received less attention. A recent whole genome analysis of annotated Drosophila melanogaster genes was specifically designed to identify empirically validated genes that have no clearly homologous gene-related sequences in D. melanogaster or its close relatives (Levine et al. 2006). We refer to this class of orphan genes as ''de novo,'' to suggest the possibility that they may derive from ancestrally noncoding sequence. Such genes would likely have novel functions that had recently evolved under directional selection in D. melanogaster. Levine et al. (2006) proposed that there are a minimum of five such genes in D. melanogaster and/ or D. simulans that are probably absent from D. yakuba, D. erecta, and D. anannasae. These D. melanogaster/ D. simulans putative de novo gene...

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“…The well-characterized chimeric gene jingwei is a copy of the Adh gene with new 59 exons that confer preference for novel substrates (Long and Langley 1993;Long et al 1999;Wang et al 2000;Zhang et al 2004). Analysis of evolutionary rates in three Adh-derived chimeric genes in various Drosophila species reveals elevated rates of replacement substitutions after chimera formation that are consistent with positive selection driving amino acid replacements in young chimeric genes ( Jones and Begun 2005).…”

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confidence: 88%

Formation and Longevity of Chimeric and Duplicate Genes inDrosophila melanogaster

Rogers

Bedford²,

Hartl

2009

Genetics

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Historically, duplicate genes have been regarded as a major source of novel genetic material. However, recent work suggests that chimeric genes formed through the fusion of pieces of different genes may also contribute to the evolution of novel functions. To compare the contribution of chimeric and duplicate genes to genome evolution, we measured their prevalence and persistence within Drosophila melanogaster. We find that $80.4 duplicates form per million years, but most are rapidly eliminated from the genome, leaving only 4.1% to be preserved by natural selection. Chimeras form at a comparatively modest rate of $11.4 per million years but follow a similar pattern of decay, with ultimately only 1.4% of chimeras preserved. We propose two mechanisms of chimeric gene formation, which rely entirely on local, DNA-based mutations to explain the structure and placement of the youngest chimeric genes observed. One involves imprecise excision of an unpaired duplication during large-loop mismatch repair, while the other invokes a process akin to replication slippage to form a chimeric gene in a single event. Our results paint a dynamic picture of both chimeras and duplicate genes within the genome and suggest that chimeric genes contribute substantially to genomic novelty.

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Parallel evolution of chimeric fusion genes

Cited by 64 publications

References 40 publications

A novel testis ubiquitin-binding protein gene arose by exon shuffling in hominoids

A novel testis ubiquitin-binding protein gene arose by exon shuffling in hominoids

Evidence forde NovoEvolution of Testis-Expressed Genes in theDrosophila yakuba/Drosophila erectaClade

Formation and Longevity of Chimeric and Duplicate Genes inDrosophila melanogaster

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