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1.
Nat Ecol Evol ; 8(4): 761-776, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38472432

RESUMO

Shared genetic polymorphisms between populations and species can be ascribed to ancestral variation or to more recent gene flow. Here, we mapped shared polymorphisms in Saccharomyces cerevisiae and its sister species Saccharomyces paradoxus, which diverged 4-6 million years ago. We used a dense map of single-nucleotide diagnostic markers (mean distance 15.6 base pairs) in 1,673 sequenced S. cerevisiae isolates to catalogue 3,852 sequence blocks (≥5 consecutive markers) introgressed from S. paradoxus, with most being recent and clade-specific. The highly diverged wild Chinese S. cerevisiae lineages were depleted of introgressed blocks but retained an excess of individual ancestral polymorphisms derived from incomplete lineage sorting, perhaps due to less dramatic population bottlenecks. In the non-Chinese S. cerevisiae lineages, we inferred major hybridization events and detected cases of overlapping introgressed blocks across distinct clades due to either shared histories or convergent evolution. We experimentally engineered, in otherwise isogenic backgrounds, the introgressed PAD1-FDC1 gene pair that independently arose in two S. cerevisiae clades and revealed that it increases resistance against diverse antifungal drugs. Overall, our study retraces the histories of divergence and secondary contacts across S. cerevisiae and S. paradoxus populations and unveils a functional outcome.


Assuntos
Polimorfismo Genético , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Hibridização Genética
2.
Genes (Basel) ; 13(6)2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35741808

RESUMO

Aging is one of the hallmarks of multiple human diseases, including cancer. We hypothesized that variations in the number of copies (CNVs) of specific genes may protect some long-living organisms theoretically more susceptible to tumorigenesis from the onset of cancer. Based on the statistical comparison of gene copy numbers within the genomes of both cancer-prone and -resistant species, we identified novel gene targets linked to tumor predisposition, such as CD52, SAT1 and SUMO. Moreover, considering their genome-wide copy number landscape, we discovered that microRNAs (miRNAs) are among the most significant gene families enriched for cancer progression and predisposition. Through bioinformatics analyses, we identified several alterations in miRNAs copy number patterns, involving miR-221, miR-222, miR-21, miR-372, miR-30b, miR-30d and miR-31, among others. Therefore, our analyses provide the first evidence that an altered miRNAs copy number signature can statistically discriminate species more susceptible to cancer from those that are tumor resistant, paving the way for further investigations.


Assuntos
Variações do Número de Cópias de DNA , Predisposição Genética para Doença , MicroRNAs , Neoplasias , Suscetibilidade a Doenças , Dosagem de Genes , Genoma , Humanos , MicroRNAs/genética , Neoplasias/genética
3.
Nat Ecol Evol ; 6(4): 448-460, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35210580

RESUMO

Domestication of plants and animals is the foundation for feeding the world human population but can profoundly alter the biology of the domesticated species. Here we investigated the effect of domestication on one of our prime model organisms, the yeast Saccharomyces cerevisiae, at a species-wide level. We tracked the capacity for sexual and asexual reproduction and the chronological life span across a global collection of 1,011 genome-sequenced yeast isolates and found a remarkable dichotomy between domesticated and wild strains. Domestication had systematically enhanced fermentative and reduced respiratory asexual growth, altered the tolerance to many stresses and abolished or impaired the sexual life cycle. The chronological life span remained largely unaffected by domestication and was instead dictated by clade-specific evolution. We traced the genetic origins of the yeast domestication syndrome using genome-wide association analysis and genetic engineering and disclosed causative effects of aneuploidy, gene presence/absence variations, copy number variations and single-nucleotide polymorphisms. Overall, we propose domestication to be the most dramatic event in budding yeast evolution, raising questions about how much domestication has distorted our understanding of the natural biology of this key model species.


Assuntos
Domesticação , Saccharomycetales , Animais , Variações do Número de Cópias de DNA , Estudo de Associação Genômica Ampla , Estágios do Ciclo de Vida , Saccharomyces cerevisiae/genética , Saccharomycetales/genética
4.
Noncoding RNA ; 7(3)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34449674

RESUMO

Long non-coding RNAs are nucleotide molecules that regulate transcription in numerous cellular processes and are related to the occurrence of many diseases, including cancer. In this regard, we recently discovered a polyadenylated long non-coding RNA (named TG2-lncRNA) encoded within the first intron of the Transglutaminase type 2 gene (TGM2), which is related to tumour proliferation in human cancer cell lines. To better characterize this new biological player, we investigated the effects of its suppression in MCF-7 breast cancer cells, using siRNA treatment and RNA-sequencing. In this way, we found modifications in several networks associated to biological functions relevant for tumorigenesis (apoptosis, chronic inflammation, angiogenesis, immunomodulation, cell mobility, and epithelial-mesenchymal transition) that were originally attributed only to Transglutaminase type 2 protein but that could be regulated also by TG2-lncRNA. Moreover, our experiments strongly suggest the ability of TG2-lncRNA to directly interact with important transcription factors, such as RXRα and TP53, paving the way for several regulatory loops that can potentially influence the phenotypic behaviour of MCF-7 cells. These considerations imply the need to further investigate the relative relevance of the TG2 protein itself and/or other gene products as key regulators in the organization of breast cancer program.

5.
Sci Rep ; 11(1): 6851, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767248

RESUMO

Insects entombed in copal, the sub-fossilized resin precursor of amber, represent a potential source of genetic data for extinct and extant, but endangered or elusive, species. Despite several studies demonstrated that it is not possible to recover endogenous DNA from insect inclusions, the preservation of biomolecules in fossilized resins samples is still under debate. In this study, we tested the possibility of obtaining endogenous ancient DNA (aDNA) molecules from insects preserved in copal, applying experimental protocols specifically designed for aDNA recovery. We were able to extract endogenous DNA molecules from one of the two samples analyzed, and to identify the taxonomic status of the specimen. Even if the sample was found well protected from external contaminants, the recovered DNA was low concentrated and extremely degraded, compared to the sample age. We conclude that it is possible to obtain genomic data from resin-entombed organisms, although we discourage aDNA analysis because of the destructive method of extraction protocols and the non-reproducibility of the results.


Assuntos
Âmbar/química , DNA Antigo/análise , DNA Antigo/isolamento & purificação , Fósseis , Insetos/genética , Resinas Vegetais/química , Análise de Sequência de DNA/métodos , Animais
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