Biomedical subjects

Gianni Liti

Publications and source records attributed to Gianni Liti.

8 recordsLinked to original sources

PubMed2026

Response to divergent selection on meiotic recombination in Saccharomyces cerevisiae.

Meiotic recombination is a key driver of evolution in sexually reproducing species, reshaping genetic diversity by generating novel allelic combinations. The rate of recombination varies substantially across living organisms depending on cis- or trans-acting genetic elements, as seen in many species, including the yeast Saccharomyces cerevisiae. Here, we report on an experimental evolution-based study to better understand the factors shaping this natural variation. Starting with a genetically diverse population of S. cerevisiae, we have carried out recurrent divergent selection on recombination rate using a fluorescence-based sorting approach in four independent lineages. After ten generations, we observed an average response of recombination rate of +28% after positive selection and -24% after negative selection, within the interval used for selection. In the adjacent region, however, we observed a weaker response in the opposite direction, and no response in four other unlinked genomic regions. Whole-genome sequencing of individuals selected for high recombination revealed mixed outcomes in the four independently evolved lineages for high genome-wide recombination rates. However, all four lineages showed selection for high recombination locally, with particular haplotypes heavily favored and sequence- or structural variation-based heterozygosity selected against within the selection interval. Overall, this experimental evolution approach provides original and useful insights into the evolvability of the meiotic recombination rate and the associated genetic determinants.

Meiotic recombination↗

PubMed2026

A haploid wild yeast resource for exploring the natural ecology of Saccharomyces cerevisiae.

Saccharomyces cerevisiae occurs predominantly in the diploid state in nature, limiting genetic analyses of wild populations. Here, we establish a haploid collection from 32 Taiwanese S. cerevisiae isolates through targeted HO disruption. This resource spans predomesticated Asian wild lineages and enables the investigation of reproductive isolation and ecological trait variation. Although all pairwise hybridizations formed zygotes, many yielded reduced spore viability, revealing strong postzygotic barriers. Genome analyses associated reduced hybrid fertility with lineage-specific structural variation, including elevated levels of intra-chromosomal inversions in H413-8/TW1 and inter-chromosomal rearrangements in PD35A/CHN-V, rather than sequence divergence alone. Phenotyping revealed ecological differentiation, with TW1 favoring cooler growth and a natural hybrid exhibiting heterosis with expanded thermotolerance. Most wild strains grew poorly on maltose, whereas anthropogenic strains displayed enhanced utilization linked to MAL + regulatory alleles and maltose-specific transporters. Together, this haploid collection links structural variation and metabolic divergence to ecological and reproductive differentiation in wild S. cerevisiae.

Saccharomyces cerevisiae↗

PubMed2025

Predicting natural variation in the yeast phenotypic landscape with machine learning.

Most organismal traits result from the complex interplay of many genetic and environmental factors, making their prediction difficult. Here, we used machine learning (ML) models to explore phenotype predictions for 223 traits measured across 1011 genome-sequenced Saccharomyces cerevisiae strains isolated worldwide. We benchmarked a ML pipeline with multiple linear and non-linear models to predict phenotypes from genotypes and gene expression, and determined gradient boosting machines as the best-performing model. Gene function disruption scores and gene presence/absence emerged as best predictors, suggesting a considerable contribution of the accessory genome in controlling phenotypes. The prediction accuracy broadly varied among phenotypes, with stress resistance being easier to predict compared to growth across nutrients. ML identified relevant genomic features linked to phenotypes, including high-impact variants with established relationships to phenotypes, despite these being rare in the population. Near-perfect accuracies were achieved when other phenomics data mostly in similar conditions were used, suggesting that useful information can be conveyed across phenotypes. Overall, our study underscores the power of ML to interpret the functional outcome of genetic variants.

Genetic Variation↗

PubMed2006

Sequence diversity, reproductive isolation and species concepts in Saccharomyces.

Using the biological species definition, yeasts of the genus Saccharomyces sensu stricto comprise six species and one natural hybrid. Previous work has shown that reproductive isolation between the species is due primarily to sequence divergence acted upon by the mismatch repair system and not due to major gene differences or chromosomal rearrangements. Sequence divergence through mismatch repair has also been shown to cause partial reproductive isolation among populations within a species. We have surveyed sequence variation in populations of Saccharomyces sensu stricto yeasts and measured meiotic sterility in hybrids. This allows us to determine the divergence necessary to produce the reproductive isolation seen among species. Rather than a sharp transition from fertility to sterility, which may have been expected, we find a smooth monotonic relationship between diversity and reproductive isolation, even as far as the well-accepted designations of S. paradoxus and S. cerevisiae as distinct species. Furthermore, we show that one species of Saccharomyces--S. cariocanus--differs from a population of S. paradoxus by four translocations, but not by sequence. There is molecular evidence of recent introgression from S. cerevisiae into the European population of S. paradoxus, supporting the idea that in nature the boundary between these species is fuzzy.

Base Sequence↗

PubMed2005

Inferences of evolutionary relationships from a population survey of LTR-retrotransposons and telomeric-associated sequences in the Saccharomyces sensu stricto complex.

The Saccharomyces sensu stricto complex consists of six closely related species and one natural hybrid. Intra- and inter- species variability in repetitive elements can help elucidate the population structure and evolution of these close relatives. The chromosome positions of several telomeric associated sequences (TASs) and LTR-retrotransposons have been determined, using PFGE, in 112 isolates. Most of the repetitive elements studied are found in multiple copies in each strain, although in some subpopulations these elements are present in low copy number or are absent. Hybridization patterns and copy numbers of the repetitive elements correlate with geographic distribution. These patterns may yield interesting clues as to the origins and evolution of some TASs and retrotransposons, e.g. we can infer that Y' originated on the left end of chromosome XIV. There is strong evidence for horizontal transfer of Ty2 between S. cerevisiae and S. mikatae. Ty1 and Ty5 are either lost easily or frequently horizontally transferred. We have also found some gross chromosomal rearrangements in isolates within species and a few new natural hybrids between species, indicating that these processes occur in the wild and are not limited to conditions of human influence. DNA sequences have been deposited with the EMBL/GenBank database under Accession Nos AJ632279-AJ632293.

Base Sequence↗

PubMed2005

Yeast evolution and comparative genomics.

Recent sequencing efforts and experiments have advanced our understanding of genome evolution in yeasts, particularly the Saccharomyces yeasts. The ancestral genome of the Saccharomyces sensu stricto complex has been subject to both whole-genome duplication, followed by massive sequence loss and divergence, and segmental duplication. In addition the subtelomeric regions are subject to further duplications and rearrangements via ectopic exchanges. Translocations and other gross chromosomal rearrangements that break down syntenic relationships occur; however, they do not appear to be a driving force of speciation. Analysis of single genomes has been fruitful for hypothesis generation such as the whole-genome duplication, but comparative genomics between close and more distant species has proven to be a powerful tool in testing these hypotheses as well as elucidating evolutionary processes acting on the genome. Future work on population genomics and experimental evolution will keep yeast at the forefront of studies in genome evolution.

Evolution, Molecular↗

PubMed2004

Analysis of a Ty1-less variant of Saccharomyces paradoxus: the gain and loss of Ty1 elements.

Because Ty elements transpose through an RNA intermediate, element accumulation through retrotransposition must be regulated or offset by element loss to avoid uncontrolled genome expansion. Here we examine the fate of Ty sequences in Saccharomyces strain 337, a strain that is reported to lack Ty1 and Ty2 elements, but contains remnant solo long terminal repeats (LTRs). Although strain 337 was initially classified as Saccharomyces cerevisiae, our work indicates that this strain is more closely related to S. paradoxus. Several degenerate Ty1 and Ty2 LTRs were mapped to the same insertion sites as full-length Ty1 and Ty2 elements in S. cerevisiae, suggesting that this strain lost Ty elements by LTR-LTR recombination. Southern analysis indicates that strain 337 also lacks Ty4 and Ty5 elements. We estimated the rates of element gain and loss in this strain by introducing a single transposition-competent Ty1 element. The results indicate that Ty1 retrotransposition occurs at a much higher rate than elimination, suggesting that copy-number-dependent co-factors or environmental conditions contribute to the loss of Ty elements in this genome.

Blotting, Southern↗

PubMed2003

NEJ1 prevents NHEJ-dependent telomere fusions in yeast without telomerase.

In a search for genes involved in cell-type-dependent chromosome instability, we have found a role for NEJ1, a regulator of nonhomologous end joining (NHEJ), in cells that survive in the absence of telomerase. In yeast, NHEJ is regulated by mating-type status through NEJ1, which is repressed in a/alpha cells. For efficient NHEJ, NEJ1 is required as part of a complex with LIF1 and DNL4, which catalyzes DNA ligation. In haploid cells without telomerase, we find that the absence of NEJ1 results in high frequencies of circular chromosomes in type II survivors (i.e., those typified by lengthened telomere repeat tracts). These telomere fusion events are DNL4 dependent. NEJ1 therefore has a role in protecting telomeres from end fusions by NHEJ in the absence of telomerase that contrasts with its role in promoting repair at sites of DNA double-strand breaks.

Cells, Cultured↗