Increased rates of protein evolution and asymmetric deceleration after the whole-genome duplication in yeasts

Ascencio, Diana; Ochoa, Soledad; Delaye, Luis; DeLuna, Alexander

doi:10.1186/s12862-017-0895-1

Cited by 21 publications

(17 citation statements)

References 61 publications

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“…Instead, this query was found to show only a strong reciprocal negative GI with its paralog SREBF2, highlighting the functional redundancy between the paralog pair (Figure 2e, Table S2 ) and suggesting that SREBF2 may regulate some of the transcriptional targets of SREBF1 as previously described previously (Shimano & Sato, 2017; Horton et al, 2008). Furthermore, the imbalanced number of GIs between SREBF1 and SREBF2 may point towards asymmetric paralog evolution, whereby duplicated genes gain or lose functional roles at different rates while maintaining partially redundant functions, a process previously observed in yeast and human cells (Zhou et al , 2014; VanderSluis et al , 2010; Ascencio et al , 2017).…”

Section: Resultsmentioning

confidence: 91%

Systematic mapping of genetic interactions for de novo fatty acid synthesis

Aregger

Billmann

et al. 2019

Preprint

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28The de novo synthesis of fatty acids has emerged as a therapeutic target for various 29 diseases including cancer. While several translational efforts have focused on direct 30 perturbation of de novo fatty acid synthesis, only modest responses have been associated 31 with mono-therapies. Since cancer cells are intrinsically buffered to combat metabolic 32 stress, cells may adapt to loss of de novo fatty acid biosynthesis. To explore cellular 33 response to defects in fatty acid synthesis, we used pooled genome-wide CRISPR 34 screens to systematically map genetic interactions (GIs) in human HAP1 cells carrying a 35 loss-of-function mutation in FASN, which catalyzes the formation of long-chain fatty acids. 36FASN mutant cells showed a strong dependence on lipid uptake that was reflected by 37 negative GIs with genes involved in the LDL receptor pathway, vesicle trafficking, and 38 protein glycosylation. Further support for these functional relationships was derived from 39 additional GI screens in query cell lines deficient for other genes involved in lipid 40 metabolism, including LDLR, SREBF1, SREBF2, ACACA. Our GI profiles identified a 41 potential role for a previously uncharacterized gene LUR1 (C12orf49) in exogenous lipid 42 uptake regulation. Overall, our data highlights the genetic determinants underlying the 43 cellular adaptation associated with loss of de novo fatty acid synthesis and demonstrate 44 the power of systematic GI mapping for uncovering metabolic buffering mechanisms in 45 human cells. 65cells adapt to perturbation of de novo fatty acid synthesis could help identify new 66 targetable vulnerabilities that may inform novel therapeutic strategies or biomarker 67 approaches. 69Mapping genetic interaction (GI) networks provides a powerful approach for identifying the 70 functional relationships between genes and their corresponding pathways. The systematic 71 exploration of pairwise GIs in model organisms revealed that GIs often occur among 72 4 functionally related genes and that GI profiles organize a hierarchy of functional modules 73 (Costanzo et al, 2016; Fischer et al, 2015). Thus, GI mapping has become an effective 74 strategy for identifying functional modules and annotating the roles of previously 75 uncharacterized genes. Model organism GI mapping has also provided insight into the 76 mechanistic basis of cellular plasticity or phenotypic switching that occurs as cells evolve 77 within their environments (Harrison et al, 2007; Szappanos et al, 2011). Accordingly, the 78 insights gained through systematic interrogation of GIs have fuelled significant interest to 79 leverage these approaches towards functionally annotating the human genome. 81Recent technological advances using CRISPR-Cas enable the systematic mapping of GIs 82 in human cells (Wright et al, 2016; Doench, 2018). Here, we explore genome-wide GI 83 screens within the context of human query mutant cells defective for de novo fatty acid 84 synthesis. We systematically mapped genome-wide GI profiles for six genes involved in ...

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Section: Resultsmentioning

confidence: 91%

Systematic mapping of genetic interactions for de novo fatty acid synthesis

Aregger

Billmann

et al. 2019

Preprint

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“…One reason is that the S. cerevisiae genome contains more ZT-than KLE-derived sequences, possibly due to biased gene conversion that replaced some KLE-derived sequences with homeologous ZT-derived ones 67, 68 . Finding that S. cerevisiae results from an allopolyploidy, rather than an autopolyploidy as originally believed, means that calculations of the relative rates of evolution of its ohnologue pairs 82 may need revision.…”

Section: Common Themes From Recent Reconstructions Of Ancient Whole-gmentioning

confidence: 99%

“…Asymmetries in the fates of DNA duplicates occur at multiple levels after ancient allopolyploidies: Patterns of gene loss, retention and mutation may differ markedly in the sub-genomes derived from each parent of the original hybrid 82 . A striking example is the tetraploid X. laevis in which large- and small-scale losses of DNA differ to such an extent that chromosomes derived from one parental species are markedly shorter than chromosomes from the other 60 .…”

Section: Common Themes From Recent Reconstructions Of Ancient Whole-gmentioning

confidence: 99%

“…Retained ohnologue gene families are strikingly enriched in signalling and regulatory proteins in plants, fungi and animals 8, 82– 85 : For example, ancestral WGDs that were identified recently for the fungi Mucor circinelloides and Phycomyces blakesleeanus resulted in increased proportions of genes whose transcription is regulated by light 86 . In humans, while only approximately 25% of genes are ohnologues stemming from the 2R-WGD, ~66% of protein kinases and nearly 90% of well-characterised 14-3-3-binding phosphoproteins are ohnologues; and developmental regulators and post-synaptic density (PSD) brain proteins are also highly enriched in ohnologues 87– 92 .…”

Section: Common Themes From Recent Reconstructions Of Ancient Whole-gmentioning

confidence: 99%

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Recent advances in understanding the roles of whole genome duplications in evolution

MacKintosh

Ferrier

2017

F1000Res

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Ancient whole-genome duplications (WGDs)— paleopolyploidy events—are key to solving Darwin’s ‘abominable mystery’ of how flowering plants evolved and radiated into a rich variety of species. The vertebrates also emerged from their invertebrate ancestors via two WGDs, and genomes of diverse gymnosperm trees, unicellular eukaryotes, invertebrates, fishes, amphibians and even a rodent carry evidence of lineage-specific WGDs. Modern polyploidy is common in eukaryotes, and it can be induced, enabling mechanisms and short-term cost-benefit assessments of polyploidy to be studied experimentally. However, the ancient WGDs can be reconstructed only by comparative genomics: these studies are difficult because the DNA duplicates have been through tens or hundreds of millions of years of gene losses, mutations, and chromosomal rearrangements that culminate in resolution of the polyploid genomes back into diploid ones (rediploidisation). Intriguing asymmetries in patterns of post-WGD gene loss and retention between duplicated sets of chromosomes have been discovered recently, and elaborations of signal transduction systems are lasting legacies from several WGDs. The data imply that simpler signalling pathways in the pre-WGD ancestors were converted via WGDs into multi-stranded parallelised networks. Genetic and biochemical studies in plants, yeasts and vertebrates suggest a paradigm in which different combinations of sister paralogues in the post-WGD regulatory networks are co-regulated under different conditions. In principle, such networks can respond to a wide array of environmental, sensory and hormonal stimuli and integrate them to generate phenotypic variety in cell types and behaviours. Patterns are also being discerned in how the post-WGD signalling networks are reconfigured in human cancers and neurological conditions. It is fascinating to unpick how ancient genomic events impact on complexity, variety and disease in modern life.

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“…While in molecular systematics, phylogenomics is usually used to infer the evolutionary relationship of species using genome-scale sequencing data[5]. Uniting these two disparate definitions, phylogenomics is now widely regarded as the molecular phylogenetic analysis of genome-scale data sets[6], which can be used for predicting gene function[7-10], inferring evolutionary patterns of macromolecules[11-13], establishing the relationships and divergence times of genes/species[14, 15], exploring the genome duplications[16-19], and so on.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary patterns of 64 vertebrate genomes (species) revealed by phylogenomics analysis of protein-coding gene families

Song

Han

Lin

2020

Preprint

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BackgroundRecent studies have demonstrated that phylogenomics is an important basis for answering many fundamental evolutionary questions. With more high-quality whole genome sequences published, more efficient phylogenomics analysis workflows are required urgently.ResultsTo this end and in order to capture putative differences among evolutionary histories of gene families and species, we developed a phylogenomics workflow for gene family classification, gene family tree inference, species tree inference and duplication/loss events dating. Our analysis framework is on the basis of two guiding ideas: 1) gene trees tend to be different from species trees but they influence each other in evolution; 2) different gene families have undergone different evolutionary mechanisms. It has been applied to the genomic data from 64 vertebrates and 5 out-group species. And the results showed high accuracy on species tree inference and few false-positives in duplication events dating.ConclusionsBased on the inferred gene duplication and loss event, only 9∼16% gene families have duplication retention after a whole genome duplication (WGD) event. A large part of these families have ohnologs from two or three WGDs. Consistent with the previous study results, the gene function of these families are mainly involved in nervous system and signal transduction related biological processes. Specifically, we found that the gene families with ohnologs from the teleost-specific (TS) WGD are enriched in fat metabolism, this result implyng that the retention of such ohnologs might be associated with the environmental status of high concentration of oxygen during that period.

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Increased rates of protein evolution and asymmetric deceleration after the whole-genome duplication in yeasts

Cited by 21 publications

References 61 publications

Systematic mapping of genetic interactions for de novo fatty acid synthesis

Systematic mapping of genetic interactions for de novo fatty acid synthesis

Recent advances in understanding the roles of whole genome duplications in evolution

Evolutionary patterns of 64 vertebrate genomes (species) revealed by phylogenomics analysis of protein-coding gene families

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