Search bioRxiv⌕ Search

Biology subjects

Perret, M.

Publications and source records attributed to Perret, M..

7 recordsLinked to original sources

Silver spoon effect: early-life environment and adult survival in a primate.

Early environmental conditions can have long-lasting effects on survival and reproductive fitness. Using a 23 year-long monitoring data set of captive mouse lemur's life history traits, we tested a relationship between maternal allocation to offspring (N = 1365) and their adulthood survival. Maternal characteristics such as age or body condition did not affect allocation to offspring whatever the litter size (1 to 3). Although birth mass depended on size and composition of the litters, mouse lemur survival was highly correlated with body mass acquired after weaning in both sexes, through potential sibling competition. Moreover, female's reproductive success correlated with this body mass and was consistently associated with increased longevity. These findings suggest the presence of a silver spoon effect under constant captive conditions. However, cumulative effects of genetic and adulthood social conditions strongly interact to affect adult survival. Deaths related to intra- or inter-sexes aggressive social interactions may outweigh effect of early environment and therefore minimize the silver-spoon effect on captive mouse lemur's survival. However, having a high body mass after weaning appeared to be a determinant factor in individual survival for mouse lemurs.

physiology↗

A primate model organism for cardiac arrhythmias identifies a magnesium transporter in pacemaker function

Cardiac arrhythmias afflict tens of millions of people, causing one-fifth of all deaths1. Although mouse models have aided understanding of some pacemaker genes and arrhythmias2,3, mice are not known to naturally acquire arrhythmias, and the substantial differences between mouse and human cardiac anatomy and physiology have limited their utility in preclinical studies and pharmacological testing2,4. To establish a primate genetic model organism for arrhythmias, we carried out an electrocardiographic (ECG) screen of over 350 lab and wild mouse lemurs (Microcebus spp.), an emerging model organism that is among the smallest, fastest-reproducing, and most abundant primates5. Twenty-two lemurs (6.2%) were identified with eight different naturally-occurring arrhythmias resembling human ECG pathologies (SSS, PACs, Afib, PVCs, NSVT, STD, iTWs, STE). Pedigree construction showed two were familial, premature atrial contractions (PACs)/atrial fibrillation (Afib) and sick sinus syndrome (SSS), an episodic bradycardia. Genome sequencing of the SSS pedigree mapped the disease locus to a 1.4 Mb interval on chromosome 7 and supported autosomal recessive Mendelian inheritance. The most appealing candidate gene in the interval was SLC41A2, a little studied magnesium transporter6,7. SLC41A2 is expressed in human iPSC-derived sinoatrial node cells (iSANC) and localizes to the sarcoplasmic reticulum. Although mouse SLC41A2 knockouts do not show a cardiac pacemaker phenotype8, CRISPR-mediated SLC41A2 knockout altered human iSANC magnesium dynamics and slowed their calcium transient firing rate. The results suggest SLC41A2 functions cell autonomously and primate-specifically in cardiac pacemaker cells, and that intracellular magnesium dynamics have a crucial but previously unappreciated role in setting pacemaker rate. Thus, mouse lemur is a valuable model for discovering new genes, molecules, and mechanisms of the primate pacemaker, and for identifying novel candidate genes and therapeutic targets for human arrhythmias. The approach can be used to elucidate other primate diseases and traits.

genetics↗

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↗

Parental age at conception on mouse lemurs offspring longevity:sex-specific maternal effects

Parental age at conception often influences offsprings longevity, a phenomenon referred as the "Lansing effect" described in large variety of organisms. But, the majority of the results refer to the survival of juveniles, mainly explained by an inadequate parental care by the elderly parents, mostly the mothers. Studies on the effect of parental age on offsprings longevity in adulthood remain few, excepted in humans for whom effects of parental age are variable according to statistical models or socioeconomic environments. In a small primate which the longevity reaches up to 12 years, we investigated the effects of parental age at conception on the longevity of offspring (N = 278) issued from parents with known longevity. None of the postnatal parameters, including body mass, influenced offsprings longevity. Mothers age at conception significantly affected offsprings longevity in males but not females. By contrast, fathers age at conception did not influence offsprings longevity. When considering the age of the breeding pairs at conception, the older the mother, the lower the longevity of male offspring with a minimum when the father was aged. No such correlation was observed for female offspring. Lastly, the longevity of female offspring was significantly positively related to the longevity of both parents. Compared with current studies, the surprisingly minor effect of fathers age and the major impact of mothers age on male offspring survival, despite favourable conditions, were discussed in relation with the highly seasonal reproduction in mouse lemurs.

evolutionary biology↗

Tabula Microcebus: A transcriptomic cell atlas of mouse lemur, an emerging primate model organism

Mouse lemurs are the smallest, fastest reproducing, and among the most abundant primates, and an emerging model organism for primate biology, behavior, health and conservation. Although much has been learned about their physiology and their Madagascar ecology and phylogeny, little is known about their cellular and molecular biology. Here we used droplet- and plate-based single cell RNA-sequencing to profile 226,000 cells from 27 mouse lemur organs and tissues opportunistically procured from four donors clinically and histologically characterized. Using computational cell clustering, integration, and expert cell annotation, we defined and biologically organized over 750 mouse lemur molecular cell types and their full gene expression profiles. These include cognates of most classical human cell types, including stem and progenitor cells, and the developmental programs for spermatogenesis, hematopoiesis, and other adult tissues. We also described dozens of previously unidentified or sparsely characterized cell types and subtypes. We globally compared cell type expression profiles to define the molecular relationships of cell types across the body, and explored primate cell and gene expression evolution by comparing mouse lemur cell transcriptomes to those of human, mouse, and macaque. This revealed cell type specific patterns of primate specialization, as well as many cell types and genes for which lemur provides a better human model than mouse. The atlas provides a cellular and molecular foundation for studying this primate model organism, and establishes a general approach for other emerging model organisms.

genetics↗

Adult survival is reduced when endogenous period deviates from 24h in a non-human primate (Microcebus murinus), depending on sex and season

SummaryCircadian rhythms are ubiquitous attributes across living organisms and allow the coordination of internal biological functions with optimal phases of the environment, suggesting a significant adaptive advantage. The endogenous period called tau lies close to 24h and is thought to be implicated in individuals’ fitness: according to the circadian resonance theory, fitness is reduced when tau gets far to 24h. In this study, we measured the endogenous period of 142 mouse lemurs (Microcebus. murinus), and analyzed how it affects their survival. We found different effects according to sex and season. No impact of tau on mortality was found in females. However, in males, the deviation of tau from 24h substantially increased mortality, particularly during the inactive season (winter). These results, comparable to other observations in mice or drosophila, show that captive gray mouse lemurs enjoy better fitness when their circadian period closely matches the environmental periodicity. In addition to their deep implications in health and aging research, these results raise further ecological and evolutionary issues regarding the relationships between fitness and circadian clock.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology↗

Convergent changes in gene expression associated with repeated transitions between hummingbird and bee pollinated flowers

The repeated evolution of convergent floral shapes and colors in angiosperms has been largely interpreted as the response to pollinator-mediated selection to maximize attraction and efficiency of specific groups of pollinators. The genetic mechanisms contributing to certain flower traits have been studied in detail for model system species, but the extent by which flowers are free to vary and how predictable are the genetic changes underlying flower adaptation to pollinator shifts still remain largely unknown.\n\nHere, we aimed at detecting the genetic basis of the repeated evolution of flower phenotypes associated with pollinator shifts. We assembled and compared de novo transcriptomes of three phylogenetic independent pairs of Gesneriaceae species, each with contrasting flower phenotype adapted to either bee or hummingbird pollination. We assembled and analyzed a total of 14,059 genes and we showed that changes in expression in 550 of them was associated with the pollination syndromes. Among those, we observed genes with function linked to floral color, scent, shape and symmetry, as well as nectar composition. These genes represent candidates genes involved in the build-up of the convergent floral phenotypes.\n\nThis study provides the first insights into the molecular mechanisms underlying the repeated evolution of pollination syndromes. Although the presence of additional lineage-specific responses cannot be excluded, these results suggest that the convergent evolution of genes expression is involved in the convergent build-up of the pollination syndromes. Future studies aiming to directly manipulate certain genes will integrate our knowledge on the key genes for floral transitions and the pace of floral evolution.\n\nData availabilityRaw Illumina reads will be available in the Sequence Read Archive (SRA) in NCBI database. The assembled transcriptomes and their annotation will by available in DRYAD repository. Details and accession ID will be provided at the time of the manuscript acceptance.

evolutionary biology↗