Gene Dosage and Gene Duplicability

Qian, Wenfeng; Zhang, Jianzhi

doi:10.1534/genetics.108.090936

Cited by 77 publications

(72 citation statements)

References 39 publications

(47 reference statements)

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“…This suggests that haploinsufficiency for either Pcbp1 or Pcbp2 is partially compensated for by wild-type levels of the sister isoform. As Pcbp1 and Pcbp2 have similar ribonucleotide binding specificities and operate through direct interactions with target RNAs and RNA processing machinery core components (22,25), we speculate that these findings are explained by a gene dose or dosage balance effect in pathways where Pcbp1 and Pcbp2 have overlapping functions (35,62,78). Thus, our data support a weight attenuation phenotype for Pcbp1-and Pcbp2-haploinsufficient and compound haploinsufficient mice, but at present the underlying specificity for this postnatal growth defect remains undetermined.…”

Section: Fig 7 Transcriptome Analysis Of Pcbp2supporting

confidence: 55%

The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development

Ghanem

Kromer

Silverman

et al. 2016

Molecular and Cellular Biology

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f RNA-binding proteins participate in a complex array of posttranscriptional controls essential to cell type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts mammalian embryonic development remains incompletely defined, and the level of functional redundancy among subsets of these proteins remains open to question. The poly(C) binding proteins, PCBPs (␣CPs and hnRNP E proteins), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here, we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos undergo normal development until midgestation (12.5 to 13.5 days postcoitum), at which time they undergo a dramatic loss in viability associated with combined cardiovascular and hematopoietic abnormalities. Mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and nondisruptive defect in initial postpartum weight gain. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and have distinct impacts on embryonic viability and that Pcpb2 has a nonredundant in vivo role in hematopoiesis. These data further provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved an essential function(s) in the mammalian genome. P osttranscriptional control of gene expression plays a major role in eukaryotic cell type specification and organism development. RNA processing and mRNA expression are regulated in the nuclear and cytoplasmic compartments by a complex array of interactions among RNA-binding proteins, noncoding RNAs, and target transcripts (1, 2). Studies have documented the central importance of posttranscriptional controls in the programming of embryonic stem cell differentiation and somatic cell development (3-11). The critical role of posttranscriptional control of gene expression can be most clearly recognized in settings of transcriptional inactivity. For example, transcription is globally silenced in the differentiating erythroblast, and the terminal steps in erythrocyte formation are fully dependent on posttranscriptional controls over mRNA stability and translation (12-14). Studies of posttranscriptional controls in this and other models have relied heavily upon a variety of in vitro experimental platforms to define mechanisms and biochemical pathways. While highly informative, such studies do not address the in vivo relevance and nonredundant functions of RNA-binding proteins in physiologically intact environments.The PCBPs (also known as ␣CPs and heterogeneous ribonucleoprotein [hnRNP] E proteins) are a widely expressed and multifunctional family of RNA-binding proteins (15-19) that bind numerous erythroid and nonerythroid mRNAs (20,21). Studies focused on globin gene expression have revealed that t...

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Section: Fig 7 Transcriptome Analysis Of Pcbp2supporting

confidence: 55%

The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development

Ghanem

Kromer

Silverman

et al. 2016

Molecular and Cellular Biology

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“…Genes that require dosage balance tend not to duplicate successfully via individual gene duplication (IGD), but can be duplicated via WGD, because only the latter does not disrupt dosage balance. Given these considerations, one may predict that duplicates generated from WGD have a different adaptation pattern from duplicates generated from IGD (Papp et al 2003;Wapinski et al 2007;Qian and Zhang 2008). We compared the gains of fitness contribution from duplicates generated by WGD and those generated by IGD.…”

Section: Similar Adaptation Patterns From Different Modes Of Duplicationmentioning

confidence: 99%

Genomic evidence for adaptation by gene duplication

2014

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Gene duplication is widely believed to facilitate adaptation, but unambiguous evidence for this hypothesis has been found in only a small number of cases. Although gene duplication may increase the fitness of the involved organisms by doubling gene dosage or neofunctionalization, it may also result in a simple division of ancestral functions into daughter genes, which need not promote adaptation. Hence, the general validity of the adaptation by gene duplication hypothesis remains uncertain. Indeed, a genome-scale experiment found similar fitness effects of deleting pairs of duplicate genes and deleting individual singleton genes from the yeast genome, leading to the conclusion that duplication rarely results in adaptation. Here we contend that the above comparison is unfair because of a known duplication bias among genes with different fitness contributions. To rectify this problem, we compare homologous genes from the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. We discover that simultaneously deleting a duplicate gene pair in S. cerevisiae reduces fitness significantly more than deleting their singleton counterpart in S. pombe, revealing postduplication adaptation. The duplicates-singleton difference in fitness effect is not attributable to a potential increase in gene dose after duplication, suggesting that the adaptation is owing to neofunctionalization, which we find to be explicable by acquisitions of binary protein-protein interactions rather than gene expression changes. These results provide genomic evidence for the role of gene duplication in organismal adaptation and are important for understanding the genetic mechanisms of evolutionary innovation.

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“…The existence of conserved paralogous genes could be beneficial in increasing gene dosage (29 -32), maintaining the dosage balance of expressed proteins involved in multi-protein complexes and in regulatory networks of signal transduction and transcription (33)(34)(35)(36), and buffering against deleterious mutations in either one of the duplicate genes (37)(38)(39). Similar expression levels between the two yeast clades irrespective of gene duplication is inconsistent with the first theory, holding that an increase in gene dosage could be advantageous and therefore promote the fixation of duplicate genes.…”

Section: Discussionmentioning

confidence: 99%

“…Duplicate gene pairs in the minor group that are characterized by conserved sequences and slow evolution rates (21,26) and include genes encoding many cytoplasmic ribosomal proteins. The evolutionary role and mechanism of retention of duplicate genes with conserved sequences-that is, increasing protein abundance (gene dosage) (29 -32), dosage balance within protein complexes and regulatory networks (33)(34)(35)(36), and amelioration of risks arising from harmful mutations in either duplicate gene (37)(38)(39) -remain controversial (40 -42). Comparative analyses of protein abundance across yeast species are expected to provide insights into whether the presence of conserved duplicate genes confers an evolutionary advantage with respect to protein dosage.…”

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confidence: 99%

Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication

Kito

Ito

Nohara

et al. 2016

Molecular & Cellular Proteomics

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Omics analysis is a versatile approach for understanding the conservation and diversity of molecular systems across multiple taxa. In this study, we compared the proteome expression profiles of four yeast species (Saccharomyces cerevisiae, Saccharomyces mikatae, Kluyveromyces waltii, and Kluyveromyces lactis) grown on glucose-or glycerol-containing media. Conserved expression changes across all species were observed only for a small proportion of all proteins differentially expressed between the two growth conditions. Two Kluyveromyces species, both of which exhibited a high growth rate on glycerol, a nonfermentative carbon source, showed distinct species-specific expression profiles. In K. waltii grown on glycerol, proteins involved in the glyoxylate cycle and gluconeogenesis were expressed in high abundance. In K. lactis grown on glycerol, the expression of glycolytic and ethanol metabolic enzymes was unexpectedly low, whereas proteins involved in cytoplasmic translation, including ribosomal proteins and elongation factors, were highly expressed. These marked differences in the types of predominantly expressed proteins suggest that K. lactis optimizes the balance of proteome resource allocation between metabolism and protein synthesis giving priority to cellular growth. In S. cerevisiae, about 450 duplicate gene pairs were retained after whole-genome duplication. Intriguingly, we found that in the case of duplicates with conserved sequences, the total abundance of proteins encoded by a duplicate pair in S. cerevisiae was similar to that of protein encoded by nonduplicated ortholog in Kluyveromyces yeast. Genome-wide analysis of multiple organisms is one of the most useful approaches to uncover both the conservation and divergence of biological processes with respect to evolutionary history. Transcriptomic studies using DNA microarrays or deep-sequencing techniques have not only characterized the expression profiles of cell-type and -state specific genes involved in many biological processes, the have also revealed the expression patterns of genes involved in a variety among different species (1). Proteomic analysis, for which mass spectrometry is one of the most powerful and widely used analytical techniques (2), can provide much more direct evidence of both conservation and divergence of expression profiles across multiple species.Interspecies comparative proteomic studies with mass spectrometry have been hitherto carried out in primates (3, 4), yeasts (5), and a variety of other model organisms (6 -9). Abundance of the core proteome, for which orthologs have been identified in all organisms investigated, are well conserved across a wide range model organisms, including yeasts, plants, worms, flies, and humans (7). The profiles of orthologous protein abundance appear to be more conserved than profiles of transcript abundance in chimpanzees and humans (4), worms and flies (6), and many other prokaryotes and eukaryotes (8), suggesting that there is more selection pressure on protein expression than transcript e...

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Gene Dosage and Gene Duplicability

Cited by 77 publications

References 39 publications

The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development

The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development

Genomic evidence for adaptation by gene duplication

Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication

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