Evolution of the recombination regulator PRDM9 in minke whales

Abstract

Background PRDM9 is a key regulator of meiotic recombination in most metazoans, responsible for reshuffling parental genomes. During meiosis, the PRDM9 protein recognizes and binds specific target motifs via its array of C2H2 zinc-fingers encoded by a rapidly evolving minisatellite. The gene coding for PRDM9 is the only speciation gene identified in vertebrates to date and shows high variation, particularly in the DNA-recognizing positions of the zinc-finger array, within and between species. Across all vertebrate genomes studied for PRDM9 evolution, only one genome lacks variability between repeat types – that of the North Pacific minke whale. This study aims to understand the evolution and diversity of Prdm9 in minke whales, which display the most unusual genome reference allele of Prdm9 so far discovered in mammals. Results Minke whales possess all the features characteristic of PRDM9-directed recombination, including complete KRAB, SSXRD and SET domains and a rapidly evolving array of C2H2-type-Zincfingers (ZnF) with evidence of rapid evolution, particularly at DNA-recognizing positions that evolve under positive diversifying selection. Seventeen novel PRDM9 variants were identified within the Antarctic minke whale species, plus a single distinct PRDM9 variant in Common minke whales – shared across North Atlantic and North Pacific minke whale subspecies boundaries. Conclusion The PRDM9 ZnF array evolves rapidly, in minke whales, with at least one DNA-recognizing position under positive selection. Extensive PRDM9 diversity is observed, particularly in the Antarctic in minke whales. Common minke whales shared a specific Prdm9 allele across subspecies boundaries, suggesting incomplete speciation by the mechanisms associated with PRDM9 hybrid sterility.

Natural variation inPrdm9affecting hybrid sterility phenotypes

“…Allelic diversity of Prdm9 in mice in this study and, as well as the PRDM9 Hu “humanized” from (D avies et al . 2016) (tree) neighbor-joining tree based on Hamming-Distances computed on the full-length nucleotide repeat sequences coding for C 2 H 2 ZNFs of PRDM9 using repeatR (D amm et al . 2022).…”

“…To reflect Prdm9 evolution more accurately, we, therefore, applied an algorithm that computes Hamming Distances between minisatellite repeat, which not only takes point mutations and small indels but also within-repeat-unit processes (w mut =1), as well as repeat-unit insertions and deletions (w indel =3.5) and even repeat-unit duplication and slippage (w slippage =1.75) into account (V ara et al . 2019; D amm et al . 2022).…”

“…The phylogeny on all alleles tested for hybrid sterility phenotypes in (M ukaj et al . 2020) and this publication was computed using the R package “repeatR” from https://mpievolbio-it.pages.gwdg.de/repeatr/ (D amm et al . 2022).…”

“…As such, can be used as a measure of genetic distance. We computed two distance matrices for each type of repeat, as in (D amm et al . 2022).…”

Meiotic Recognition of Evolutionarily Diverged Homologs: Chromosomal Hybrid Sterility Revisited

“…In mice, humans ( Baudat et al 2010 ; Myers et al 2010 ; Parvanov et al 2010 ), and many other vertebrates ( Baker et al 2017 ; Cavassim et al 2022 ; Damm et al 2022 ), the genomic localizations of SPO11-driven DSBs are predetermined by the PRDM9 histone methyl transferase catalytic activity ( fig. 2 C ).…”