Reenacting a mouse genetic evolutionary arms race in yeast reveals SLXL1/SLX compete with SLY1/2 for binding to Spindlins.

The house mouse X and Y chromosomes have recently acquired high copy number, rapidly evolving gene families representing an evolutionary arms race. This arms race between proteins encoded by X-linked / and Y-linked gene families can distort male offspring sex ratio, but how these proteins compete remains unknown. Here, we report how / and encoded proteins compete in a protein family-specific and dose-dependent manner using yeast.

Malic enzyme 1 knockout has no deleterious phenotype and is favored in the male germline under standard laboratory conditions.

Malic Enzyme 1 (ME1) plays an integral role in fatty acid synthesis and cellular energetics through its production of NADPH and pyruvate. As such, it has been identified as a gene of interest in obesity, type 2 diabetes, and an array of epithelial cancers, with most work being performed in vitro. The current standard model for ME1 loss in vivo is the spontaneous Mod-1 null allele, which produces a canonically inactive form of ME1.

Out with the old, in with the new: Meiotic driving of sex chromosome evolution.

Chromosomal regions with meiotic drivers exhibit biased transmission (> 50 %) over their competing homologous chromosomal region. These regions often have two prominent genetic features: suppressed meiotic crossing over and rapidly evolving multicopy gene families. Heteromorphic sex chromosomes (e.

X-linked palindromic gene families 4930567H17Rik and Mageb5 are dispensable for male mouse fertility.

Mammalian sex chromosomes are enriched for large, nearly-identical, palindromic sequences harboring genes expressed predominately in testicular germ cells. Discerning if individual palindrome-associated gene families are essential for male reproduction is difficult due to challenges in disrupting all copies of a gene family. Here we generate precise, independent, deletions to assess the reproductive roles of two X-linked palindromic gene families with spermatid-predominant expression, 4930567H17Rik and Mageb5.

Mechanisms of meiotic drive in symmetric and asymmetric meiosis.

Meiotic drive, the non-Mendelian transmission of chromosomes to the next generation, functions in asymmetric or symmetric meiosis across unicellular and multicellular organisms. In asymmetric meiosis, meiotic drivers act to alter a chromosome's spatial position in a single egg. In symmetric meiosis, meiotic drivers cause phenotypic differences between gametes with and without the driver.

X-Linked Signature of Reproductive Isolation in Humans is Mirrored in a Howler Monkey Hybrid Zone.

Reproductive isolation is a fundamental step in speciation. While sex chromosomes have been linked to reproductive isolation in many model systems, including hominids, genetic studies of the contribution of sex chromosome loci to speciation for natural populations are relatively sparse. Natural hybrid zones can help identify genomic regions contributing to reproductive isolation, like hybrid incompatibility loci, since these regions exhibit reduced introgression between parental species.

Genomic Structure, Evolutionary Origins, and Reproductive Function of a Large Amplified Intrinsically Disordered Protein-Coding Gene on the X Chromosome () in Mice.

Mouse sex chromosomes are enriched for co-amplified gene families, present in tens to hundreds of copies. Co-amplification of / on the X chromosome and on the Y chromosome are involved in dose-dependent meiotic drive, however the role of other co-amplified genes remains poorly understood. Here we demonstrate that the co-amplified gene family on the X chromosome, , along with two additional partial gene annotations, is actually part of a larger transcription unit, which we name is harbored in a 229 kb amplicon that represents the ancestral state as compared to a 525 kb Y-amplicon containing the rearranged contains a 25,011 nucleotide open reading frame, predominantly expressed in round spermatids, predicted to encode an 871 kD protein.

Large X-Linked Palindromes Undergo Arm-to-Arm Gene Conversion across Mus Lineages.

Large (>10 kb), nearly identical (>99% nucleotide identity), palindromic sequences are enriched on mammalian sex chromosomes. Primate Y-palindromes undergo high rates of arm-to-arm gene conversion, a proposed mechanism for maintaining their sequence integrity in the absence of X-Y recombination. It is unclear whether X-palindromes, which can freely recombine in females, undergo arm-to-arm gene conversion and, if so, at what rate.

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

The mammalian sex chromosomes harbor an abundance of newly acquired ampliconic genes, although their functions require elucidation [1-9]. Here, we demonstrate that the X-linked Slx and Slxl1 ampliconic gene families represent mouse-specific neofunctionalized copies of a meiotic synaptonemal complex protein, Sycp3. In contrast to the meiotic role of Sycp3, CRISPR-loxP-mediated multi-megabase deletions of the Slx (5 Mb) and Slxl1 (2.

Male mice with large inversions or deletions of X-chromosome palindrome arms are fertile and express their associated genes during post-meiosis.

Large (>10 kb) palindromic sequences are enriched on mammalian sex chromosomes. In mice, these palindromes harbor gene families (≥2 gene copies) expressed exclusively in post-meiotic testicular germ cells, a time when most single-copy sex-linked genes are transcriptionally repressed. This observation led to the hypothesis that palindromic structures or having ≥2 gene copies enable post-meiotic gene expression.

CRISPR-mediated isolation of specific megabase segments of genomic DNA.

Megabase-sized, complex, repetitive regions of genomes are poorly studied, due to the technical and computational challenges inherent to both assembling precise reference sequences and accurately assessing structural variation across contiguous megabase DNA regions. Here we describe a strategy to overcome these challenges, CISMR (CRISPR-mediated isolation of specific megabase-sized regions of the genome), which enables us to perform targeted isolation of contiguous megabase-sized segments of the genome. Direct sequencing of the purified DNA segments can have >100-fold enrichment of the target region, thus enabling the exploration of both DNA sequence and structural diversity of complex genomic regions in any species.

A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary.

The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, particularly in organisms with a segregated germline. We characterized the gene regulatory program of meiotic prophase as it occurs in the mouse fetal ovary.

Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes.

We sequenced the MSY (male-specific region of the Y chromosome) of the C57BL/6J strain of the laboratory mouse Mus musculus. In contrast to theories that Y chromosomes are heterochromatic and gene poor, the mouse MSY is 99.9% euchromatic and contains about 700 protein-coding genes.

Independent specialization of the human and mouse X chromosomes for the male germ line.

We compared the human and mouse X chromosomes to systematically test Ohno's law, which states that the gene content of X chromosomes is conserved across placental mammals. First, we improved the accuracy of the human X-chromosome reference sequence through single-haplotype sequencing of ampliconic regions. The new sequence closed gaps in the reference sequence, corrected previously misassembled regions and identified new palindromic amplicons.

The mouse X chromosome is enriched for multicopy testis genes showing postmeiotic expression.

According to the prevailing view, mammalian X chromosomes are enriched in spermatogenesis genes expressed before meiosis and deficient in spermatogenesis genes expressed after meiosis. The paucity of postmeiotic genes on the X chromosome has been interpreted as a consequence of meiotic sex chromosome inactivation (MSCI)--the complete silencing of genes on the XY bivalent at meiotic prophase. Recent studies have concluded that MSCI-initiated silencing persists beyond meiosis and that most genes on the X chromosome remain repressed in round spermatids.

Targeted gene deletion and phenotypic analysis of the Drosophila melanogaster seminal fluid protease inhibitor Acp62F.

Internally fertilizing organisms transfer a complex assortment of seminal fluid proteins, a substantial fraction of which are proteolysis regulators. In mammals, some seminal protease inhibitors have been implicated in male infertility and these same molecular classes of protease inhibitors are also found in Drosophila seminal fluid. Here, we tested the reproductive functions of the Drosophila melanogaster seminal fluid protease inhibitor Acp62F by generating a precise deletion of the Acp62F gene.

An ectopic expression screen reveals the protective and toxic effects of Drosophila seminal fluid proteins.

In Drosophila melanogaster, seminal fluid regulates the reproductive and immune responses of mated females. Some seminal fluid proteins may provide protective functions to mated females, such as antimicrobial activity and/or stimulation of antimicrobial gene expression levels, while others appear to have negative effects, contributing to a "cost of mating." To identify seminal proteins that could participate in these phenomena, we used a systemic ectopic expression screen to test the effects on unmated females of proteins normally produced by the male accessory gland (Acps).

Bovine seminal plasma proteins PDC-109, BSP-A3, and BSP-30-kDa share functional roles in storing sperm in the oviduct.

On ejaculation, sperm become coated with proteins secreted by the male accessory sex glands. In the bull, these proteins consist predominantly of the bovine seminal plasma family of proteins (BSPs): PDC-109 (BSP-A1/-A2), BSP-A3, and BSP-30-kDa. PDC-109 plays a role in forming an oviductal sperm reservoir by enabling sperm to bind to oviductal epithelium.

A scan of molecular variation leads to the narrow localization of a selective sweep affecting both Afrotropical and cosmopolitan populations of Drosophila melanogaster.

Drosophila melanogaster originated in tropical Africa but has achieved a cosmopolitan distribution in association with human habitation. Cosmopolitan populations of D. melanogaster are known to have reduced genetic variation, particularly on the X chromosome.

Comparative structural modeling and inference of conserved protein classes in Drosophila seminal fluid.

The constituents of seminal fluid are a complex mixture of proteins and other molecules, most of whose functions have yet to be determined and many of which are rapidly evolving. As a step in elucidating the roles of these proteins and exposing potential functional similarities hidden by their rapid evolution, we performed comparative structural modeling on 28 of 52 predicted seminal proteins produced in the Drosophila melanogaster male accessory gland. Each model was characterized by defining residues likely to be important for structure and function.