New perspectives on the causes and consequences of male meiotic drive

Abstract

Gametogenesis is vulnerable to selfish genetic elements that bias their transmission to the next generation by cheating meiosis. These so-called meiotic drivers are widespread in plants, animals, and fungi and can impact genome evolution. Here, we summarize recent progress on the causes and consequences of meiotic drive in males, where selfish elements attack vulnerabilities in spermatogenesis. Advances in genomics provide new insights into the organization and dynamics of driving chromosomes in natural populations. Common themes, including small RNAs, gene duplications, and heterochromatin, emerged from these studies. Interdisciplinary approaches combining evolutionary genomics with molecular and cell biology are beginning to unravel the mysteries of drive and suppression mechanisms. These approaches also provide insights into fundamental processes in spermatogenesis and chromatin regulation.

Figure 1.. Rapid evolutionary dynamics of driving chromosomes on short evolutionary timescales.

A) The Segregation Distorter system of Drosophila melanogaster is an autosomal male drive supergene. Patterns of genetic variation (π – average pairwise nucleotide diversity per site) reveal the presence of a large supergene that swept through a Zambian population. The supergene begins at the main drive locus on chromosome 2L called Sd-RanGAP and extends beyond the distal inversion breakpoint of a nested pair of inversions (In(2R)Mal; position denoted by orange box on x-axis) specific to these African SD chromosomes. Strong epistatic selection between Sd-RanGAP and some enhancer of drive in or near the inversion on chromosome 2R hold the complex together (Figure represents data from Navarro Dominguez et al.[3]). B) Dynamics of the Paris SR system in D. simulans. The driver, X^SR, emerged in East Africa and has spread to North Africa and Europe. Populations where X^SR has been detected are indicated by a gray circle. Populations with longitudinal data (those with pie charts) reveal changes in X^SR frequency over periods as short as 4 years. The frequencies of X^SR and the X^ST (standard, non-driving X chromosome) are indicated in red and blue, respectively, and black arrows connect the sample frequencies at different time points. In the last two decades, while X^SR frequency declined in the Indian Ocean, it emerged and then increased in frequency in North Africa and Europe. As the X^SR spread, sensitive Y chromosomes (purple) were replaced by resistant Y chromosomes (green; inset plot above the map). The figure based on results in [14,15].

Figure 2.. Post-meiotic male drivers involve a disruption in sperm chromatin.

A) Spermatogenesis in Drosophila melanogaster. Testes are coiled tubes with germline stem cells (GSCs) in the hub at the apical tip of the testis, which divide asymmetrically to produce another GSC and a daughter germ cell. Germ cells (circles) develop while surrounded somatic cyst cells (curved lines), where they undergo four rounds of mitotic divisions and two meiotic divisions with incomplete cytokinesis. After meiosis, the round haploid spermatids enter spermiogenesis where they tightly package their DNA with sperm basic nuclear proteins as they differentiate into mature sperm. B) Sperm shrink 200-fold as their chromatin transitions from histones, to transition proteins, to small sperm-specific histone-like proteins called protamines (the histone-to-protamine transition). Many sperm basic nuclear proteins are involved in this chromatin transition. Following the transition, spermatids individualize into mature sperm and are deposited in the seminal vesicle (s.v. in panel A). C) The cytological phenotype of many postmeiotic male drivers manifests after meiosis in sperm chromatin. The SD system of Drosophila melanogaster has a defect in progression through the histone-to-protamine transition. The immunofluorescence image (C) shows nuclei around the time of individualization (DAPI, greyscale) from driving SD/+ testes in the following genotype: SD-Mad/In(2R)Gla; ProtB-DsRed/+ (ProtB-DsRed from [54]). To create this image, testes were fixed (4% formaldehyde in 0.1% Triton- X-100 in PBS), blocked (2% bovine serum albumin in PBST), mounted, and then imaged with a Leica SP5 laser scanning confocal microscope. These flies have strong segregation distortion (98% offspring are SD). Their nuclei show a loss of protamines (ProtB-DsRed, red) in half of their spermatids (outlined with dotted line). Some nuclei are also misshapen (arrows). D) The RDC complex licenses transcription from complex satellite DNA loci like the Rsp locus that is the target of SD. These transcripts are processed into piRNAs and could be important for regulating satellite chromatin [33,36]. These fundamental insights into satellite DNA regulation may inform studies of drive mechanisms and suppression.

Figure 3.. Gene duplication and positive selection are signatures of genetic conflict.

A) Recurring bouts of drive and suppression can trigger evolutionary arms races that lead to positive selection and gene duplication. B) The co-amplification of X- and Y-linked genes can occur due to conflicts over segregation ratios. C) Chang et al. [27] identified orthologs of sperm basic nuclear proteins in Drosophila species. The protamine-like genes ddbt, Mst77F, and Prtl99C are components of mature sperm chromatin that are essential for male fertility that show dynamic evolution across the Drosophila phylogeny. The columns indicate the genomic location and copy number status of orthologs. Orthologs with syntenic genomic positions are represented with a cyan box if there is a single autosomal copy and dark blue boxes if it is duplicated on an autosome (either in tandem or to a different chromosome). Orthologs that moved to the X or Y chromosome and amplified to multiple copies are indicated in orange and magenta, respectively. Orthologs that are not present are represented in grey. This figure is redrawn based on Chang et al. [27].

Box 1 Figure 1.. Gene editing to dissect mechanisms of drive.

Schematic showing the CRISPR-loxP-mediated gene editing technique used to generate multi-megabase deletions and duplications in house mice (based on Figure 2A–B and 3A of [53]).