Computational modelling of meiotic entry and commitment

In response to developmental and environmental conditions, cells exit the mitotic cell cycle and enter the meiosis program to generate haploid gametes from diploid germ cells. Once cells decide to enter the meiosis program they become irreversibly committed to the completion of meiosis irrespective of the presence of cue signals. How meiotic entry and commitment occur due to the dynamics of the regulatory network is not well understood. Therefore, we constructed a mathematical model of the regulatory network that controls the transition from mitosis to meiosis in Schizosaccharomyces pombe. Upon nitrogen starvation, yeast cells exit mitosis and undergo conjugation and meiotic entry. The model includes the regulation of Mei2, an RNA binding protein required for conjugation and meiotic entry, by multiple feedback loops involving Pat1, a kinase that keeps cells in mitosis, and Ste11, a transcription activator required for the sexual differentiation. The model accounts for various experimental observations and demonstrates that the activation of Mei2 is bistable, which ensures the irreversible commitment to meiosis. Further, we show by integrating the meiosis-specific regulation with a cell cycle model, the dynamics of cell cycle exit, G1 arrest and entry into meiosis under nitrogen starvation. © 2017 The Author(s)

How to make a sex chromosome

Sex chromosomes can evolve once recombination is halted between a homologous pair of chromosomes. Owing to detailed studies using key model systems, we have a nuanced understanding and a rich review literature of what happens to sex chromosomes once recombination is arrested. However, three broad questions remain unanswered. First, why do sex chromosomes stop recombining in the first place? Second, how is recombination halted? Finally, why does the spread of recombination suppression, and therefore the rate of sex chromosome divergence, vary so substantially across clades? In this review, we consider each of these three questions in turn to address fundamental questions in the field, summarize our current understanding, and highlight important areas for future work

Convergence and divergence in sex-chromosome evolution

A sequence assembly of the chicken W chromosome enables reconstruction of the gene content of the W chromosome across 14 bird species and shows striking similarities in the maintenance of broadly expressed and dosage-sensitive genes on highly degenerate sex chromosomes in both birds and mammals. However, the chicken W chromosome is not enriched for genes with expression in female-specific tissues, providing an intriguing contrast to the acquisition and amplification of genes with testis-specific expression on mammalian Y chromosomes and suggesting that the inheritance of chromosomes solely through females or males can lead to different evolutionary outcomes

Selective single molecule sequencing and assembly of a human Y chromosome of African origin

Mammalian Y chromosomes are often neglected from genomic analysis. Due to their inherent assembly difficulties, high repeat content, and large ampliconic regions, only a handful of species have their Y chromosome properly characterized. To date, just a single human reference quality Y chromosome, of European ancestry, is available due to a lack of accessible methodology. To facilitate the assembly of such complicated genomic territory, we developed a novel strategy to sequence native, unamplified flow sorted DNA on a MinION nanopore sequencing device. Our approach yields a highly continuous assembly of the first human Y chromosome of African origin. It constitutes a significant improvement over comparable previous methods, increasing continuity by more than 800%. Sequencing native DNA also allows to take advantage of the nanopore signal data to detect epigenetic modifications in situ. This approach is in theory generalizable to any species simplifying the assembly of extremely large and repetitive genomes.This study was supported by the Spanish Ministry of Economy and Competitiveness with Proyectos de I+D “Excelencia” y Proyectos de I+D+I “Retos Investigación” BFU2014-55090-P awarded to T.M.-B. and O.F., Centro de Excelencia Severo Ochoa 2013–2017 and Centro de Excelencia Maria de Maeztu 2016–2019. We acknowledge the support from the CERCA Programme of the Generalitat de Catalunya, institutional support from the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) through the Instituto de Salud Carlos III, from the Generalitat de Catalunya through the Departament de Salut and Departament d’Empresa i Coneixement, and co-financing by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) with funds from the European Regional Development Fund (ERDF) corresponding to the 2014–2020 Smart Growth Operating Program. L.F.K.K. is supported by an FPI fellowship associated with BFU2014-55090-P (MINECO/FEDER, UE). M.K. is supported by a Deutsche Forschungsgemeinschaft (DFG) fellowship (KU 3467/1-1). T.M.-B. is supported by BFU2017-86471-P (MINECO/FEDER, UE), U01 MH106874 grant, Howard Hughes International Early Career, Obra Social “La Caixa” and Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya. D.J. is supported by a Juan de la Cierva fellowship (FJCI-2016-29558) from MICINN