Evolutionarily conserved pachytene piRNA loci are highly divergent among modern humans.

Deniz M Özata,Kaili Fan,Yasin Kaymaz,Tianxiong Yu,Haiwei Mou,Cansu Colpan,Phillip D Zamore,Zhiping Weng,Ildar Gainetdinov,Katharine Cecchini,Pei-Hsuan Wu,Alper Kucukural

doi:10.1038/s41559-019-1065-1

Abstract

In the fetal mouse testis, PIWI Interacting RNAs (piRNAs) guide PIWI proteins to silence transposons, but after birth, most post-pubertal pachytene piRNAs map to the genome uniquely and are thought to regulate genes required for male fertility. In human males, the developmental classes, precise genomic origins, and transcriptional regulation of post-natal piRNAs remain undefined. Here, we demarcate the genes and transcripts that produce post-natal piRNAs in human juvenile and adult testes. As in mouse, human A-MYB drives transcription of both pachytene piRNA precursor transcripts and the mRNAs encoding piRNA biogenesis factors. Although human piRNA genes are syntenic to those in other placental mammals, their sequences are poorly conserved. In fact, pachytene piRNA loci are rapidly diverging even among modern humans. Our findings suggest that during mammalian evolution, pachytene piRNA genes are under few selective constraints. We speculate that pachytene piRNA diversity may provide a hitherto unrecognized driver of reproductive isolation.

Highlights

Human PIWI Interacting RNAs (piRNAs)-producing loci have been roughly mapped using piRNA sequences[1,2,22,23], but the classes, precise genomic locations, or transcription factors regulating human piRNA loci remain unknown
To begin to classify the piRNAs produced during human spermatogenesis, we used strandspecific RNA sequencing to assemble the RNA transcripts and small (25–31 nt) RNA sequencing to define the piRNA repertoire of the post-natal human testis (Supplementary Table 1)
Pachytene piRNA genes are transcribed at the onset of the pachynema when the A-Myb gene is activated[14,21]

Summary

Introduction

Human piRNA-producing loci have been roughly mapped using piRNA sequences[1,2,22,23], but the classes, precise genomic locations, or transcription factors regulating human piRNA loci remain unknown. ChIP data suggest that A-MYB coordinates the transcription of ~55% of human pachytene piRNA-producing genes and macaque piRNA-producing genes. A-MYB binds the promoters of ~74% of genes encoding piRNA biogenesis proteins in macaques but only ~30% in humans. One-third of human pachytene piRNA-producing genes can be found at the syntenic location in the genomes of other Eutherian mammals; half are restricted to primates; ~18% are human-specific. While pachytene piRNA gene promoters are well conserved, piRNA sequences themselves have diverged rapidly among placental mammals. The sequences of pachytene piRNAs vary within the human population more than any other genomic feature. We speculate that pachytene piRNA diversity may provide a hitherto unrecognized driver of Eutherian reproductive isolation

Methods

Results

Conclusion