The pioneering role of PRDM9 indel mutations in tarsier evolution

Abstract

PRDM9 is currently the sole speciation gene found in vertebrates causing hybrid sterility probably due to incompatible alleles. Its role in defining the double strand break loci during the meiotic prophase I is crucial for proper chromosome segregation. Therefore, the rapid turnover of the loci determining zinc finger array seems to be causative for incompatibilities. We here investigated the zinc finger domain-containing exon of PRDM9 in 23 tarsiers. Tarsiers, the most basal extant haplorhine primates, exhibit two frameshifting indels at the 5′-end of the array. The first mutation event interrupts the reading frame and function while the second compensates both. The fixation of this allele variant in tarsiers led to hypothesize that de- and reactivation of the zinc finger domain drove the speciation in early haplorhine or tarsiiform primates. Moreover, the high allelic diversity within Tarsius points to multiple effects of genetic drift reflecting their phylogeographic history since the Miocene.

PRDM9 and Its Role in Genetic Recombination

“…If recombinationally active PRDM9 was indeed present in our most primitive vertebrate ancestors, its sporadic presence in the vertebrate evolutionary tree indicates that PRDM9’s function in recombination has been lost and/or gained multiple times in the course of vertebrate evolution. Primate examples of gains and losses include human PRDM7 , a gene duplication with three amino acid substitutions in the SET domain, one of which practically destroys the ability to methylate both H3K4 and H3K36, along with loss of most of the zinc finger array [69], and tarsiers ( Tarsius syrichta), which exhibit two frame shift mutations, one of which cancels the other to regenerate an active sequence [10]. In ruminants, multiple gene duplications have created several PRDM9 paralogues, at least two of which appear to be recombinationally active [19, 21, 70].…”

PRDM9, a driver of the genetic map

“…The initial finding of PRDM9-mediated DSB localization in mice and humans has been extended to other primates [ 39 , 40 , 69 ]. PRDM9 is also predicted to specify meiotic recombination sites in other vertebrate species [ 70 ], such as equids [ 34 ], bovines [ 35 , 36 ], some fish species, turtles, snakes and lizards, and coelacanth [ 71 ].…”

Pinpointing the PRDM9-PRDM7 Gene Duplication Event During Primate Divergence

“…The zinc finger array of this gene has undergone rapid evolution with regard to the number of tandem repeats as well as its DNA-binding amino acids, and has been associated with positive selection ( Oliver et al, 2009 ; Thomas et al, 2009 ; Myers et al, 2010 ). Phylogenies of PRDM9 show that the 5′-most zinc fingers of all studied primates are distinct from other canonical C2H2 zinc finger sequences ( Schwartz et al, 2014 ; Heerschop et al, 2016 ).…”

“…Its expression is restricted to male and female germlines during meiosis I ( Hayashi et al, 2005 ). PRDM9 has been studied in several haplorrhine primate species ( Oliver et al, 2009 ; Auton et al, 2012 ; Groeneveld et al, 2012 ; Schwartz et al, 2014 ; Heerschop et al, 2016 ; Stevison et al, 2016 ). The zinc finger array of this gene has undergone rapid evolution with regard to the number of tandem repeats as well as its DNA-binding amino acids, and has been associated with positive selection ( Oliver et al, 2009 ; Thomas et al, 2009 ; Myers et al, 2010 ).…”