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Biology subjects

Bonnet, A.

Publications and source records attributed to Bonnet, A..

7 recordsLinked to original sources

An extensive and unbiased genome-wide scan for parent-of-origin expressed genes in the pig clarifies the conservation landscape of genomic imprinting

Genomic imprinting, a mechanism resulting in parent-of-origin expression of genes through epigenetic regulation, intersects with a broad range of biological fields including evolution, molecular genetics and epigenetics and determinism of complex traits. Although next generation sequencing technologies enable nowadays to detect imprinted genes in a genome-wide manner, a wide spectrum of this phenomena is evaluated only in humans and mice. Here, we propose to map genes showing a parental expression bias in hypothalamus, muscle and placenta in piglets around birth using an extensive and unbiased strategy that relied on reciprocal crosses, genetics reconstruction of parental phases after imputation and statistical analyses discriminating parent-of-origin from allele-specific expression. We detected 440 unique genes with a weak to exclusive parental expression bias including 114 unique genes with an imbalance ratio above 25:75. About thirty imprinted genes are common to human and/or mice and an equivalent number is shared between tissues, suggesting an overall weak conservation landscape of genomic imprinting. Interestingly, we identified novel parent-of-origin expressed genes involved in neurodevelopmental (PITRM1, Pitrilysin Metallopeptidase 1) and fetal growth (FAM20B, Glycosaminoglycan Xylosylkinase and POU6F2, POU Class 6 Homeobox 2) functions. In addition, deeper analyses of specific loci likely highlighted lineage-specific imprinted genes such as a Zinc Finger Protein 300-like gene as well as specific imprinted isoforms of COPG2 (COPI Coat Complex Subunit Gamma 2), a gene showing conflicting data in the literature. Altogether, our results bring pig as the most comprehensively and exhaustively documented species for genomic imprinting after human and mice organisms. A weak conservation of this mechanism across species and tissues suggested a distinction between a small number of core imprinted genes and others parent-of-origin expressed genes that seemed subjected to evolutionary forces for acquiring their imprinting status either in a lineage-specific or tissue-specific manner.

genomics↗

Effects of host sex, age and behaviour on co-infection patterns in a wild ungulate

Recent zoonotic disease emergences reveal the importance of studying wildlife parasite communities. As wild hosts frequently harbour diverse parasite species, understanding the drivers of multiple infection patterns in free-ranging hosts is critical for elucidating the ecological and epidemiological dynamics of parasite communities. In this study, we analysed co-infection patterns in European roe deer (Capreolus capreolus) inhabiting a fragmented rural landscape in southwestern France. Using data from 130 GPS-tracked roe deer, we examined the influence of proximity to livestock, host activity levels, age, sex, and between-parasite interactions on the presence of 11 parasitic taxa. Hierarchical modelling of species communities (HMSC) revealed that proximity to livestock significantly increased the likelihood of infection with orofecally transmitted parasites (Toxoplasma gondii, gastrointestinal parasites). Sex and age were other key predictors, with males and juveniles exhibiting a higher frequency of parasite presence, likely influenced by hormonal and immune system differences. Activity levels showed distinct age-related effects, with higher activity levels being positively associated with increased parasite prevalence in yearlings, but not in adults. In contrast, parasite association patterns within individual hosts were weak, suggesting minimal interactions between parasite species. Our findings highlight the interplay between exposure and susceptibility in shaping co-infection patterns and underscore the value of hierarchical modelling approaches in multi-parasite systems. Key FindingsO_LIParasite communities, studied in 130 GPS monitored roe deer, revealed frequent co-infection. C_LIO_LIProximity to livestock increased the risk of infection by parasite taxa shared with domestic animals. C_LIO_LIFor several parasitic taxa, males and younger roe deer had a higher probability of infection. C_LIO_LIThe effect of host activity on parasite infection was dependent on roe deer age. C_LIO_LIOnly slight between-parasite interactions were detected within individual hosts. C_LI

ecology↗

Massive detection of cryptic recessive genetic defects in cattle mining millions of life histories

We present a data-mining framework designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes. In particular, we describe disorders associated with NOA1 and RFC5 mutations for the first time in vertebrates. The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.

genetics↗

Using accelerometers to infer behaviour of cryptic species in the wild

Accelerometery is revolutionising the field of behavioural ecology through its capacity to detect the fine-scale movements of animals resulting from their behaviour. Because it is often difficult to infer the behaviour of wildlife on a continuous basis, particularly for cryptic species, accelerometers potentially provide powerful tools for remote monitoring of their behavioural responses to the environment. The goal of this study was to provide a detailed, calibrated methodology, including practical guidelines, to infer the behaviour of free-ranging animals from acceleration data. This approach can be employed to reliably infer the time budget of species that are difficult to observe in certain environments or at certain times of the day. To this end, we trained several behavioural classification algorithms with accelerometer data obtained on captive roe deer, then validated these algorithms with data obtained on free-ranging roe deer, and finally predicted the time-budgets of a substantial sample of unobserved free-ranging roe deer in a human-dominated landscape. The best classification algorithm was the Random Forest which predicted five behavioural classes with a high overall level of accuracy ({approx} 90%). Except for grooming (34-38%), we were able to predict the behaviour of free-ranging roe deer over the course of a day with high accuracy, in particular, foraging head down, running, walking and immobile (68-94%). Applied to free-ranging individuals, the classification allowed us to estimate, for example, that roe deer spent about twice as much time foraging head-down, walking or running during dawn and dusk than during daylight or night-time. By integrating step by step calibration and validation of accelerometer data prior to application in the wild, our approach is transferable to other free-ranging animals for predicting key behaviours in cryptic species.

animal behavior and cognition↗

A nuclear pore sub-complex restricts the propagation of Ty retrotransposons by limiting their transcription

Beyond their canonical function in nucleocytoplasmic exchanges, nuclear pore complexes (NPCs) regulate the expression of protein-coding genes. Here, we have implemented transcriptomic and molecular methods to specifically address the impact of the NPC on retroelements, which are present in multiple copies in genomes. We report a novel function for the Nup84 complex, a core NPC building block, in specifically restricting the transcription of LTR-retrotransposons in yeast. Nup84 complex-dependent repression impacts both Copia and Gypsy Ty LTR-retrotransposons, all over the S. cerevisiae genome. Mechanistically, the Nup84 complex restricts the transcription of Ty1, the most active yeast retrotransposon, through the tethering of the SUMO-deconjugating enzyme Ulp1 to NPCs. Strikingly, the modest accumulation of Ty1 RNAs caused by Nup84 complex loss-of-function is sufficient to trigger an important increase of Ty1 cDNA levels, resulting in massive Ty1 retrotransposition. Altogether, our studies expand our understanding of the complex interactions between retrotransposons and the NPC, and highlight the importance for the cells to keep retrotransposon under tight transcriptional control. AUTHOR SUMMARYRetroelements, which replicate by reverse transcription of their RNA into a cDNA that is integrated into the host genetic material, play an important role in the plasticity of eukaryotic genomes. The study of yeast retrotransposons has led to the identification of host factors that limit retroelement mobility, including components of the nuclear pore complex (NPC), most of them still awaiting mechanistic characterization. Here, we investigated the contribution of the Nup84 complex, a core NPC scaffold, to retrotransposon biology in budding yeast. Our findings uncover that the Nup84 complex restricts the transcription of phylogenetically-distinct Ty retroelements. By focusing on Ty1 retrotransposons, we provide evidence that repression by the Nup84 complex depends on the maintenance at the NPC of the SUMO-protease Ulp1, an essential enzyme of the SUMO pathway with multiple targets in the transcription machinery. We finally show that this transcriptional control is critical for genome dynamics, since a small increase in the accumulation of Ty1 RNAs leads to massive retrotransposition. Our data reveal that although relatively abundant, Ty transcripts are limiting for retrotransposition, underscoring the importance of a tight control of their expression. They also characterize a new non-canonical function of NPCs, confirming their connection with genome expression and stability.

molecular biology↗

The Ty1 integrase nuclear localization signal is necessary and sufficient for retrotransposon targeting to tRNA genes

Integration of transposable elements into the genome is mutagenic. Mechanisms that target integration into relatively safe locations and minimize deleterious consequences for cell fitness have emerged during evolution. In budding yeast, the integration of the Ty1 LTR retrotransposon upstream of RNA polymerase III (Pol III)-transcribed genes requires the interaction between the AC40 subunit of Pol III and Ty1 integrase (IN1). Here we show that the IN1-AC40 interaction involves a short linker sequence in the bipartite nuclear localization signal (bNLS) of IN1. Mutations in this sequence do not impact the frequency of Ty1 retromobility, instead they decrease the recruitment of IN1 to Pol III-transcribed genes and the subsequent integration of Ty1 at these loci. The replacement of Ty5 retrotransposon targeting sequence by the IN1 bNLS induces Ty5 integration into Pol III-transcribed genes. Therefore, the IN1 bNLS is both necessary and sufficient to confer integration site specificity on Ty1 and Ty5 retrotransposons.

molecular biology↗

Modeling Spatial Genomic Interactions with the Hawkes model

The spatial localization of many DNA-protein interactions is now available thanks to the development of ChIP-Seq, and their investigation calls for adapted statistical methods. Many methods were developped for peak calling, but few were proposed for the downstream analysis of peak-like data, whereas the spatial structure of such data may contain relevant biological information, like binding constraints for instance. Associations between the occurrences of two genomic features are usually assessed by overlaps, but here we propose a statistical model to precisely quantify the spatial interactions between the location of binding events. Our methodology relies on a multivariate spatial process, the Hawkes model, that can also be interpreted in terms of a graphical model to highlight spatial dependencies between genomic features. Using our method, we explore the chromatinian landscape of replication origins, and we highlight attractive and repulsive patterns that can be related to the regulation of the spatial program of replication.

bioinformatics↗