Biology subjects

Petrizzelli, M.

Publications and source records attributed to Petrizzelli, M..

3 recordsLinked to original sources

bioRxiv2020

Data integration uncovers the metabolic bases of phenotypic variation in yeast

The relationship between different levels of integration is a key feature for understanding the genotype-phenotype map.Here, we describe a novel method of integrated data analysis that incorporates protein abundance data into constraint-based modeling to elucidate the biological mechanisms underlying phenotypic variation. Specifically, we studied yeast genetic diversity at three levels of phenotypic complexity in a population of yeast obtained by pairwise crosses of eleven strains belonging to two species, Saccha-romyces cerevisiae and S. uvarum. The data included protein abundances, integrated traits (life-history/fermentation) and computational estimates of metabolic fluxes.Results highlighted that the negative correlation between production traits such as population carrying capacity (K) and traits associated with growth and fermentation rates (Jmax) is explained by a differential usage of energy production pathways: a high K was associated with high TCA fluxes, while a high Jmax was associated with high glycolytic fluxes. Enrichment analysis of protein sets confirmed our results.This powerful approach allowed us to identify the molecular and metabolic bases of integrated trait variation, and therefore has a broad applicability domain.View Full Text

systems biology↗

bioRxiv2019

Probabilities of multilocus genotypes in SIBrecombinant inbred lines

Recombinant Inbred Lines (RILs) are obtained through generations of inbreeding until all alleles are fixed. In 1931 Haldane and Waddington published a landmark paper where they provided the probabilities of achieving any combination of alleles in 2-way RILs for 2 and 3 loci. In the case of SIB RILs where sisters and brothers are crossed at each generation, there has been no progress in treating 4 or more loci, a limitation we overcome here without much increase in complexity. In the general situation of L loci, the task is to determine 2L probabilities, but we find that it is necessary to first calculate the 4L \"identical by descent\" (IBD) probabilities that a RIL inherits at each locus its DNA from one of the four originating chromosomes. We show that these 4L probabilities satisfy a system of linear equations that follow from self consistency. In the absence of genetic interference - crossovers arising independently -, the associated matrix can be written explicitly in terms of the recombination rates between the different loci. We provide the matrices for L up to 4 and also include a computer program to automatically generate the matrices for higher values of L. Furthermore, our framework can be generalized to recombination rates that are different in female and male meiosis which allows us to show that the Haldane and Waddington 2-locus formula is valid in that more subtle case if the meiotic recombination rate is taken as the average rate across female and male. Once the 4L IBD probabilities are determined, the 2L probabilities of RIL genotypes are obtained via summations of these quantities. In fine, our computer program allows to determine the probabilities of all the multilocus genotypes produced in such sibling-based RILs for L [≤] 10, a huge leap beyond the L = 3 restriction of Haldane and Waddington.

genetics↗

bioRxiv2018

Decoupling of heterosis and inbreeding variances is evidenced in yeast’s life-history and proteomic traits

Heterosis (hybrid vigor) and inbreeding depression, commonly considered as corollary phenomena, could nevertheless be decoupled under certain assumptions according to theoretical population genetics works. In order to explore this issue on real data, we analyzed the components of genetic variation in a population derived from a half-diallel cross between strains from Saccharomyces cerevisiae and S. uvarum, two related yeast species involved in alcoholic fermentation. A large number of phenotypic traits, either molecular (coming from quantitative proteomics) or related to fermentation and life-history, were measured during alcoholic fermentation. Because the parental strains were included in the design, we were able to distinguish between inbreeding effects, which measures phenotypic differences between inbred and hybrids, and heterosis, which measures phenotypic differences between a specific hybrid and the other hybrids sharing a common parent. The sources of phenotypic variation differed depending on the temperature, indicating the predominance of genotype by environment interactions. Decomposing the total genetic variance into variances of additive (intra- and inter-specific) effects, of inbreeding effects and of heterosis (intra- and inter-specific) effects, we showed that the distribution of variance components defined clear-cut groups of proteins and traits. Moreover, it was possible to cluster fermentation and life-history traits into most proteomic groups. Within groups, we observed positive, negative or null correlations between the variances of heterosis and inbreeding effects. To our knowledge, such a decoupling had never been experimentally demonstrated. This result suggests that, despite a common evolutionary history of individuals within a species, the different types of traits have been subject to different selective pressures.

systems biology↗