A Neofunctionalized X-Linked Ampliconic Gene Family Is Essential for Male Fertility and Equal Sex Ratio in Mice

Abstract

Highlights d Slx and Slxl1 are mouse lineage-specific copies of their autosomal progenitor Sycp3 d Slx and Slxl1 gene families are essential for male fertility d Changes in Slxl1 gene copy number distorts the ratio of male to female offspring d Slxl1 versus Sly competition for spindlin proteins may mediate sex-ratio distortion

Genomic structure, evolutionary origins, and reproductive function of a large amplified intrinsically disordered protein gene on the X chromosome (Laidx) in mice

“…The co-amplification of genes on the mouse X and Y chromosomes is thought to have arisen through meiotic conflict, whereby gene duplication confers a competitive advantage in X-or Y-bearing sperm [9]. An example of this phenomenon can be seen in Sly, Slx, and Slxl1 [7,9]. Characterization of Laidx reveals that, while there is considerable sequence identity between the Laidx/y-amplicons, these chromosomes produce dramatically different transcripts.…”

“…These co-amplified X-(Slx, Slxl1, Sstx, Srsx, Astx) and Y-linked (Sly, Ssty1, Ssty2, Srsy, Asty) gene families are predominantly expressed in post-meiotic testicular germ cells, suggesting an important function in reproduction and testicular germ cell development [1][2][3][4][5][6]. The co-amplification of gene families on the X and Y chromosomes is thought to have arisen because of meiotic drive, the unequal transmission of an allele to the next generation [1, 7,8]. Slx, Slxl1, and Sly are meiotic drivers, where increases in gene expression generates a competitive advantage of X-or Y-bearing sperm [7,9].…”

“…The co-amplification of gene families on the X and Y chromosomes is thought to have arisen because of meiotic drive, the unequal transmission of an allele to the next generation [1, 7,8]. Slx, Slxl1, and Sly are meiotic drivers, where increases in gene expression generates a competitive advantage of X-or Y-bearing sperm [7,9].…”

“…The Slx/Slxl1 gene family is also required for male fertility, highlighting how a coamplified gene family can become essential for male fertility [7,10]. However, little is known about the biological functions or evolutionary origins of other X-and Y-linked coamplified gene families.…”

Thewtf4meiotic driver utilizes controlled protein aggregation to generate selective cell death

“…In this model, wtf4 533 exploits protein aggregation control pathways to induce selective cell death. The Wtf4 poison forms 534 distributed toxic aggregates and the Wtf4 antidote co-assembles with the Wtf4 poison and neutralizes 535 of any other meiotic driver described to date(Grognet et al, 2014;Didion et al, 2015; Long et 537 al., 2008; Dawe et al, 2018;Rhoades et al, 2019; Dalstra et al, 2005; Hammond et al, 2012; 538Vogan et al, 2019, Chen et al, 2008Akera et al, 2017;Bauer et al, 2012; Pieper et al, 2018; 539Herrmann et al, 1999;Shen et al,2017; Yu, et al, 2018;Bauer et al, 2007; Wu et al, 1988; 540Xie, et al, 2019;Kruger et al, 2019;Lin et al, 2018), but there are very few mechanistically541 characterized gamete-killing drive systems (reviewed in Bravo Núñez et al, 2018). 542 543 Continued investigation into how fission yeast and budding yeast species handle Wtf4 544 aggregates may elucidate important biological features of the two yeasts as well as a more 545 detailed Wtf4 mechanism.…”