Meiotic Executioner Genes Protect the Y from Extinction

The mammalian Y chromosome has been proposed to be a wimp with impending demise should it lose sex-determining function. Changes in sex-determining switches are common in non-mammalian vertebrates, so an alternative explanation is required to explain Y chromosome persistence. The Y chromosome bears executioner genes that are essential for male meiosis, but must themselves also be subjected to meiotic silencing because they are pachytene lethal. The only heritable location that executioner genes can transpose to is the X chromosome (just 5% of the genome), where they remain subject to appropriate meiotic silencing. Transposition of executioner genes away from the Y chromosome is uncommon, posing strong evolutionary constraint for the Y to persistent. The Y has been described as a wimpy degraded relic of the X, with imminent demise should it lose sex-determining function. Why then has it persisted in almost all mammals? Here we present a novel mechanistic explanation for its evolutionary perseverance: the persistent Y hypothesis. The Y chromosome bears genes that act as their own judge, jury, and executioner in the tightly regulated meiotic surveillance pathways. These executioners are crucial for successful meiosis, yet need to be silenced during the meiotic sex chromosome inactivation window, otherwise germ cells die. Only rare transposition events to the X, where they remain subject to obligate meiotic silencing, are heritable, posing strong evolutionary constraint for the Y chromosome to persist. The Y has been described as a wimpy degraded relic of the X, with imminent demise should it lose sex-determining function. Why then has it persisted in almost all mammals? Here we present a novel mechanistic explanation for its evolutionary perseverance: the persistent Y hypothesis. The Y chromosome bears genes that act as their own judge, jury, and executioner in the tightly regulated meiotic surveillance pathways. These executioners are crucial for successful meiosis, yet need to be silenced during the meiotic sex chromosome inactivation window, otherwise germ cells die. Only rare transposition events to the X, where they remain subject to obligate meiotic silencing, are heritable, posing strong evolutionary constraint for the Y chromosome to persist. the reduction of genetic diversity at a nondeleterious locus because it is linked to a deleterious allele that is under negative selection. a structure enriched in proteins of the synaptonemal complex formed during the first meiotic division of meiosis. It is necessary to maintain associated asynaptic and achiasmatic sex chromosomes that lack a PAR (e.g., in marsupials). the process by which the single X in males and two Xs in females are balanced to have equivalent transcriptional output. the process by which a neutral allele achieves high frequency, or even fixation, within a population because it is linked to a beneficial allele that is under positive selection. a gene that if expressed during the MSCI window is lethal to the cell. a conserved process in sexually reproducing organisms that results in the production of haploid gametes. wide range of interconnected molecular mechanisms that control chromosomal pairing, synapsis as well as the formation and repair of double-strand breaks during meiosis. It includes meiotic silencing of unsynapsed chromatin (MSUC) and the spindle assembly checkpoint (SAC). transcription silencing of the X and Y chromosomes during prophase I. The X and Y form a sex body (distinct from the autosomes) that is enriched for repressive histone modifications. the process by which unsynapsed chromosomal regions undergo a process of transcriptional inactivation during prophase I. in the absence of recombination, mutations on the Y chromosome cannot be removed from the population. As more mutations accumulate on the Y, the least-mutated Y is permanently lost. This is known as a click of the ratchet. a nuclear compartment, including the X and Y chromosomes, in post-meiotic spermatids, characterized by repressive histone modifications. homologous region on the X and Y chromosomes that pair during meiosis and within which there is an obligate recombination event. This is critical for proper segregation of the X and Y. the process by which homologous chromosomes exchange genetic material during the first meiotic division. It establishes physical connections between homologs that are essential for faithful chromosomal pairing and segregation. the process by which an individual’s phenotypic sex is determined. This can be controlled by a genetic switch or environmental cues (e.g., temperature). Sex determining switches are surprisingly varied in non-mammal vertebrates. the process by which male germ cells are formed. Spermatogenesis can be divided into three stages: (i) proliferation and differentiation of spermatogonia, (ii) meiosis, and (iii) spermiogenesis, the process of spermatid maturation to spermatozoa. a gene on the Y chromosome that triggers testis development. In therian mammals this is the Sry gene.