Genic and chromosomal components of Prdm9-driven hybrid male sterility in mice (Mus musculus)

Abstract

Hybrid sterility contributes to speciation by preventing gene flow between related taxa. Prdm9, the first and only hybrid male sterility (HMS) gene known in vertebrates, predetermines the sites of recombination between homologous chromosomes and their synapsis in early meiotic prophase. The asymmetric binding of PRDM9 to heterosubspecific homologs of Mus m. musculus x Mus m. domesticus F1 hybrids and increase of PRDM9-independent DNA double-strand break (DSB) hotspots results in difficult to repair DSBs, incomplete synapsis of homologous chromosomes and meiotic arrest at the first meiotic prophase. Here we show that Prdm9 behaves as a major HMS gene in mice outside the Mus m. musculus x Mus m. domesticus F1 hybrids, in the genomes composed of Mus m. castaneus and Mus m. musculus chromosomes segregating on the Mus m. domesticus background. The Prdm9cst/dom2 (castaneus/domesticus) allelic combination secures meiotic synapsis, testes weight and sperm count within physiological limits, while the Prdm9msc1/dom2 (musculus/domesticus) males show a range of fertility impairment. Out of five quantitative trait loci contributing to the Prdm9msc1/dom2-related infertility, four control either meiotic synapsis or fertility phenotypes and one controls both, synapsis and fertility. Whole-genome genotyping of individual chromosomes showed preferential involvement of nonrecombinant musculus chromosomes in asynapsis in accordance with the chromosomal character of HMS. Moreover, we show that the overall asynapsis rate can be estimated solely from the genotype of individual males by scoring the effect of nonrecombinant musculus chromosomes. Prdm9-controlled HMS represents an example of genetic architecture of HMS consisting of genic and chromosomal components.

Speciation, Natural Selection, and Networks: Three Historians Versus Theoretical Population Geneticists

“…Mayr never appreciated this, nor did a member of the late population genetics wave, H. Allen Orr (academic genealogy: Filipchenko, Dobzhansky, Lewontin, Coyne, Orr). His paper (Orr 1996) continued to receive multiple citations, despite its disparagement of Bateson (Forsdyke 2011) and narrow focus on Dobzhansky-Muller incompatibilities (Valiskova et al 2022).…”

“…Here natural selection can operate, either prior to fertilization to produce a hybrid zygote (prezygotic reproductive isolation) or after fertilization (one form of postzygotic reproductive isolation; "hybrid incompatibility"). The latter is often referred to as a Dobzhansky-Muller incompatibility (Valiskova et al 2022) which, like prezygotic isolation, depends on the nature of parental genes.…”

Natural variation inPrdm9affecting hybrid sterility phenotypes

“…This is particularly evident for the msc6 allele, which differs from the msc1 allele in only two nucleotides coding for amino acids of the eleventh zinc finger responsible for DNA binding specificity (Figure S4); a slight difference that is nevertheless sufficient in determining whether F1-hybrids are sterile or fertile on the same genetic background. Another example of how small changes can affect fertility can be observed for msc11, which displays lower fertility, but equally differs only in a single ZNF from the Cst allele, which has been well-characterized in B6xCAST intersubspecific hybrids, and no fertility reduction has been reported (PARVANOV et al 2009;BAKER et al 2015;DIAGOURAGA et al 2018;GREY et al 2018;HINCH et al 2019;VALISKOVA et al 2022).…”

“…2018). Prdm9 is also a major hybrid sterility gene in MUS x CAS hybrids, where the synapsis rate was proportional to the level of nonrecombining MUS genetic background (V aliskova et al . 2022).…”

“…In the natural hybrid zone, a relatively young zone of secondary contact, only as few as one-third of all house mouse males displayed fertility traits below the range of the pure subspecies (T urner and H arr 2014). Five Prdm9 -dependent quantitative trait loci have been identified in intersubspecific (MUS x CAS) hybrids, segregating on DOM background (V aliskova et al . 2022).…”