ORCID Profile
0000-0001-5111-8816
Current Organisations
Princess Margaret Cancer Centre
,
University of Toronto
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 14-12-2021
DOI: 10.1111/JEB.13746
Abstract: Non‐native species experience novel selection pressures in introduced environments and may interbreed with native lineages. Species introductions therefore provide opportunities to investigate repeated patterns of adaptation and introgression across replicated contact zones. Here, we investigate genetic parallelism between multiple introduced populations of the invasive marine mussel, Mytilus galloprovincialis , in the absence (South Africa and California) and presence of hybridization with a native congener ( Mytilus planulatus in Batemans Bay and Sydney Harbour, Australia). Repeatability in post‐introduction differentiation from native‐range populations varied between genetically distinct Atlantic and Mediterranean lineages, with Atlantic‐derived introductions displaying high differentiation (max F ST 0.4) and parallelism at outlier loci. Identification of long noncoding RNA transcripts (lncRNA) additionally allowed us to clarify that parallel responses are largely limited to protein‐coding loci, with lncRNAs likely evolving under evolutionary constraints. Comparisons of independent hybrid zones revealed differential introgression most strongly in Batemans Bay, with an excess of M. galloprovincialis ancestry and resistance to introgression at loci differentiating parental lineages ( M. planulatus and Atlantic M. galloprovincialis ). Additionally, contigs putatively introgressed with ergent alleles from a closely related species, Mytilus edulis, showed stronger introgression asymmetries compared with genome‐wide trends and also erged in parallel in both Atlantic‐derived introductions. These results suggest that ergent demographic histories experienced by introduced lineages, including pre‐introduction introgression, influence contemporary admixture dynamics. Our findings build on previous investigations reporting contributions of historical introgression to intrinsic reproductive architectures shared between marine lineages and illustrate that interspecific introgression history can shape differentiation between colonizing populations and their hybridization with native congeners.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-11-2020
Abstract: Identifying the function of enhancers, DNA regions that help to regulate gene expression and evolve rapidly, has been difficult. This area of research has been h ered by the difficultly in identifying functional conservation. Wong et al. now show that despite low sequence conservation, enhancer function is strongly conserved through the animal kingdom (see the Perspective by Harmston). Transgenic expression of sponge enhancers in zebrafish and mice demonstrates that these sequences can drive cell type–specific gene expression across species. These results suggest an unexpectedly deep level of conservation of gene regulation across the animal kingdom maintained over the course of metazoan evolution. Science , this issue p. eaax8137 see also p. 657
Publisher: Springer Science and Business Media LLC
Date: 22-09-2022
DOI: 10.1038/S41588-022-01179-9
Abstract: Somatic mutations in cancer genes have been detected in clonal expansions across healthy human tissue, including in clonal hematopoiesis. However, because mutated and wild-type cells are admixed, we have limited ability to link genotypes with phenotypes. To overcome this limitation, we leveraged multi-modality single-cell sequencing, capturing genotype, transcriptomes and methylomes in progenitors from in iduals with DNMT3A R882 mutated clonal hematopoiesis. DNMT3A mutations result in myeloid over lymphoid bias, and an expansion of immature myeloid progenitors primed toward megakaryocytic-erythroid fate, with dysregulated expression of lineage and leukemia stem cell markers. Mutated DNMT3A leads to preferential hypomethylation of polycomb repressive complex 2 targets and a specific CpG flanking motif. Notably, the hypomethylation motif is enriched in binding motifs of key hematopoietic transcription factors, serving as a potential mechanistic link between DNMT3A mutations and aberrant transcriptional phenotypes. Thus, single-cell multi-omics paves the road to defining the downstream consequences of mutations that drive clonal mosaicism.
Publisher: Springer Science and Business Media LLC
Date: 09-07-2021
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.YDBIO.2016.11.013
Abstract: Animals rely on genomic regulatory systems to direct the dynamic spatiotemporal and cell-type specific gene expression that is essential for the development and maintenance of a multicellular lifestyle. Although it is widely appreciated that these systems ultimately evolved from genomic regulatory mechanisms present in single-celled stem metazoans, it remains unclear how this occurred. Here, we focus on the contribution of the non-coding portion of the genome to the evolution of animal gene regulation, specifically on recent insights from non-bilaterian metazoan lineages, and unicellular and colonial holozoan sister taxa. High-throughput next-generation sequencing, largely in bilaterian model species, has led to the discovery of tens of thousands of non-coding RNA genes (ncRNAs), including short, long and circular forms, and uncovered the central roles they play in development. Based on the analysis of non-bilaterian metazoan, unicellular holozoan and fungal genomes, the evolution of some ncRNAs, such as Piwi-interacting RNAs, correlates with the emergence of metazoan multicellularity, while others, including microRNAs, long non-coding RNAs and circular RNAs, appear to be more ancient. Analysis of non-coding regulatory DNA and histone post-translational modifications have revealed that some cis-regulatory mechanisms, such as those associated with proximal promoters, are present in non-animal holozoans, while others appear to be metazoan innovations, most notably distal enhancers. In contrast, the cohesin-CTCF system for regulating higher-order chromatin structure and enhancer-promoter long-range interactions appears to be restricted to bilaterians. Taken together, most bilaterian non-coding regulatory mechanisms appear to have originated before the ergence of crown metazoans. However, differential expansion of non-coding RNA and cis-regulatory DNA repertoires in bilaterians may account for their increased regulatory and morphological complexity relative to non-bilaterians.
Publisher: eLife Sciences Publications, Ltd
Date: 02-03-2017
Publisher: Springer Science and Business Media LLC
Date: 23-04-2019
DOI: 10.1038/S41467-019-09645-5
Abstract: Cancer evolution is fueled by epigenetic as well as genetic ersity. In chronic lymphocytic leukemia (CLL), intra-tumoral DNA methylation (DNAme) heterogeneity empowers evolution. Here, to comprehensively study the epigenetic dimension of cancer evolution, we integrate DNAme analysis with histone modification mapping and single cell analyses of RNA expression and DNAme in 22 primary CLL and 13 healthy donor B lymphocyte s les. Our data reveal corrupted coherence across different layers of the CLL epigenome. This manifests in decreased mutual information across epigenetic modifications and gene expression attributed to cell-to-cell heterogeneity. Disrupted epigenetic-transcriptional coordination in CLL is also reflected in the dysregulation of the transcriptional output as a function of the combinatorial chromatin states, including incomplete Polycomb-mediated gene silencing. Notably, we observe unexpected co-mapping of typically mutually exclusive activating and repressing histone modifications, suggestive of intra-tumoral epigenetic ersity. Thus, CLL epigenetic ersification leads to decreased coordination across layers of epigenetic information, likely reflecting an admixture of cells with erging cellular identities.
Publisher: MDPI AG
Date: 24-09-2023
Publisher: Springer Science and Business Media LLC
Date: 23-03-2020
Publisher: eLife Sciences Publications, Ltd
Date: 11-04-2017
DOI: 10.7554/ELIFE.22194
Abstract: Combinatorial patterns of histone modifications regulate developmental and cell type-specific gene expression and underpin animal complexity, but it is unclear when this regulatory system evolved. By analysing histone modifications in a morphologically-simple, early branching animal, the sponge Amphimedonqueenslandica, we show that the regulatory landscape used by complex bilaterians was already in place at the dawn of animal multicellularity. This includes distal enhancers, repressive chromatin and transcriptional units marked by H3K4me3 that vary with levels of developmental regulation. Strikingly, Amphimedon enhancers are enriched in metazoan-specific microsyntenic units, suggesting that their genomic location is extremely ancient and likely to place constraints on the evolution of surrounding genes. These results suggest that the regulatory foundation for spatiotemporal gene expression evolved prior to the ergence of sponges and eumetazoans, and was necessary for the evolution of animal multicellularity.
Publisher: MDPI AG
Date: 07-03-2018
DOI: 10.3390/NCRNA4010006
Publisher: Springer Science and Business Media LLC
Date: 1970
Publisher: Oxford University Press (OUP)
Date: 14-05-2015
Publisher: Springer Science and Business Media LLC
Date: 30-09-2021
Publisher: Informa UK Limited
Date: 25-05-2018
Publisher: Springer Science and Business Media LLC
Date: 06-2020
Location: United States of America
No related grants have been discovered for Federico Gaiti.