Abstract Gene co-expression networks are a widely used tool for summarizing transcriptomic variation between individuals, and for inferring the transcriptional regulatory pathways that mediate genotype–phenotype relationships. However, these co-expression networks must be interpreted with caution, as they can arise from multiple processes. Here, we investigate one such process, using simulations to demonstrate that hybridization and gene flow between populations can greatly modify co-expression networks. Admixture between populations produces correlated expression between genes experiencing linkage disequilibrium. This correlated expression does not reflect functional relationships between genes but rather depends on migration rates and physical linkage on chromosomes. Given the prevalence of gene flow and hybridization between divergent populations in nature, these introgression effects likely represent a significant force in network evolution, even in populations where hybridization is historical rather than contemporary. These findings emphasize the critical importance of considering both evolutionary history and genomic architecture when analyzing gene co-expression networks in natural populations.
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Evolutionary and Experimental Loss of Gene Body Methylation and Its Consequence to Gene Expression
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null (Ed.)Abstract Yarrowia lipolytica has emerged as a biomanufacturing platform for a variety of industrial applications. It has been demonstrated to be a robust cell factory for the production of renewable chemicals and enzymes for fuel, feed, oleochemical, nutraceutical and pharmaceutical applications. Metabolic engineering of this non-conventional yeast started through conventional molecular genetic engineering tools; however, recent advances in gene/genome editing systems, such as CRISPR–Cas9, transposons, and TALENs, has greatly expanded the applications of synthetic biology, metabolic engineering and functional genomics of Y. lipolytica . In this review we summarize the work to develop these tools and their demonstrated uses in engineering Y. lipolytica , discuss important subtleties and challenges to using these tools, and give our perspective on important gaps in gene/genome editing tools in Y. lipolytica .more » « less
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The genes that encode the α- and β-chain subunits of vertebrate hemoglobin have served as a model system for elucidating general principles of gene family evolution, but little is known about patterns of evolution in amniotes other than mammals and birds. Here, we report a comparative genomic analysis of the α- and β-globin gene clusters in sauropsids (archosaurs and nonavian reptiles). The objectives were to characterize changes in the size and membership composition of the α- and β-globin gene families within and among the major sauropsid lineages, to reconstruct the evolutionary history of the sauropsid α- and β-globin genes, to resolve orthologous relationships, and to reconstruct evolutionary changes in the developmental regulation of gene expression. Our comparisons revealed contrasting patterns of evolution in the unlinked α- and β-globin gene clusters. In the α-globin gene cluster, which has remained in the ancestral chromosomal location, evolutionary changes in gene content are attributable to the differential retention of paralogous gene copies that were present in the common ancestor of tetrapods. In the β-globin gene cluster, which was translocated to a new chromosomal location, evolutionary changes in gene content are attributable to differential gene gains (via lineage-specific duplication events) and gene losses (via lineage-specific deletions and inactivations). Consequently, all major groups of amniotes possess unique repertoires of embryonic and postnatally expressed β-type globin genes that diversified independently in each lineage. These independently derived β-type globins descend from a pair of tandemly linked paralogs in the most recent common ancestor of sauropsids.more » « less
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Saitou, Naruya (Ed.)Abstract Enhancers are often studied as noncoding regulatory elements that modulate the precise spatiotemporal expression of genes in a highly tissue-specific manner. This paradigm has been challenged by recent evidence of individual enhancers acting in multiple tissues or developmental contexts. However, the frequency of these enhancers with high degrees of “pleiotropy” out of all putative enhancers is not well understood. Consequently, it is unclear how the variation of enhancer pleiotropy corresponds to the variation in expression breadth of target genes. Here, we use multi-tissue chromatin maps from diverse human tissues to investigate the enhancer–gene interaction architecture while accounting for 1) the distribution of enhancer pleiotropy, 2) the variations of regulatory links from enhancers to target genes, and 3) the expression breadth of target genes. We show that most enhancers are tissue-specific and that highly pleiotropy enhancers account for <1% of all putative regulatory sequences in the human genome. Notably, several genomic features are indicative of increasing enhancer pleiotropy, including longer sequence length, greater number of links to genes, increasing abundance and diversity of encoded transcription factor motifs, and stronger evolutionary conservation. Intriguingly, the number of enhancers per gene remains remarkably consistent for all genes (∼14). However, enhancer pleiotropy does not directly translate to the expression breadth of target genes. We further present a series of Gaussian Mixture Models to represent this organization architecture. Consequently, we demonstrate that a modest trend of more pleiotropic enhancers targeting more broadly expressed genes can generate the observed diversity of expression breadths in the human genome.more » « less
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Ma, Li-Jun (Ed.)Abstract By introducing novel capacities and functions, new genes and gene families may play a crucial role in ecological transitions. Mechanisms generating new gene families include de novo gene birth, horizontal gene transfer, and neofunctionalization following a duplication event. The ectomycorrhizal (ECM) symbiosis is a ubiquitous mutualism and the association has evolved repeatedly and independently many times among the fungi, but the evolutionary dynamics enabling its emergence remain elusive. We developed a phylogenetic workflow to first understand if gene families unique to ECM Amanita fungi and absent from closely related asymbiotic species are functionally relevant to the symbiosis, and then to systematically infer their origins. We identified 109 gene families unique to ECM Amanita species. Genes belonging to unique gene families are under strong purifying selection and are upregulated during symbiosis, compared with genes of conserved or orphan gene families. The origins of seven of the unique gene families are strongly supported as either de novo gene birth (two gene families), horizontal gene transfer (four), or gene duplication (one). An additional 34 families appear new because of their selective retention within symbiotic species. Among the 109 unique gene families, the most upregulated gene in symbiotic cultures encodes a 1-aminocyclopropane-1-carboxylate deaminase, an enzyme capable of downregulating the synthesis of the plant hormone ethylene, a common negative regulator of plant-microbial mutualisms.more » « less
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