Highly dynamic temporal changes of TSPY gene copy number in aging bulls

Abstract

The Y-chromosomal TSPY gene is one of the highest copy number mammalian protein coding gene and represents a unique biological model to study various aspects of genomic copy number variations. This study investigated the age-related copy number variability of the bovine TSPY gene, a new and unstudied aspect of the biology of TSPY that has been shown to vary among cattle breeds, individual bulls and somatic tissues. The subjects of this prospective 30-month long study were 25 Holstein bulls, sampled every six months. Real-time quantitative PCR was used to determine the relative TSPY copy number (rTSPY CN) and telomere length in the DNA samples extracted from blood. Twenty bulls showed an altered rTSPY CN after 30 months, although only 9 bulls showed a significant change (4 significant increase while 5 significant decrease, P<0.01). The sequential sampling provided the flow of rTSPY CN over six observations in 30 months and wide-spread variation of rTSPY CN was detected. Although a clear trend of the direction of change was not identifiable, the highly dynamic changes of individual rTSPY CN in aging bulls were observed here for the first time. In summary we have observed a highly variable rTSPY CN in bulls over a short period of time. Our results suggest the importance of further long term studies of the dynamics of rTSPY CN variablility.

Testis-Specific Protein Y-Encoded (TSPY) Is Required for Male Early Embryo Development in Bos taurus

“…De novo recombination has been observed in other studies. Oluwole et al, 2017 have shown de novo TSPY CN differences in somatic tissues as well as changes in TSPY CN of approximately 1~1.5 fold in 26% of aging bulls [ 22 ]. These changes in TSPY CN correspond to a doubling of average TSPY CN from sperm (21 copy variations) to male blastocysts (52.1 copy variations) and a further increase in adult bulls (100 copies variations).…”

“…In bovines, bulls with higher TSPY CN showed higher fertility rates [ 20 ], whereas low TSPY CN was linked to bulls with inferior semen production [ 21 ]. TSPY CN shows temporal changes during aging both in vitro and in vivo [ 22 ], suggesting possible epigenetic recombination of TSPY . TSPY is expressed exclusively in the germ cells during embryogenesis and spermatogenesis and is present in both prenatal and adult testis [ 13 , 23 ].…”

“…Most TSPY studies have been conducted in adult and fetal tissues and cells, but not much is known about the earlier preimplantation stages of development, which are key for fertility [ 30 ], although TSPY expression has been shown at the bovine blastocyst stage. There is substantial evidence that copy number varies among brothers and changes with aging [ 22 ]. However, in early embryos, it has only been superficially examined [ 30 , 31 ].…”

Copy number variation of ZNF280AY across 21 cattle breeds and its association with the reproductive traits of Holstein and Simmental bulls

“…The transcriptional landscape of the bovine MSY has revealed that approximately 80 palindrome-like repeat units (~420 kb per unit) constitute the bovine Y ampliconic region, and each unit resides in 4 multicopy families (TSPY, ZN-F280AY, ZNF280BY, and HSFY;Chang et al, 2013), which provides an important structural foundation in favor of intra-and interpalindrome gene conversion and potentially regulates the equilibrium between gene loss and acquisition during Y chromosome evolution (Trombetta and Cruciani, 2017). Notably, regardless of the underlying cause of the temporal disparity in multicopy gene families (Oluwole et al, 2017), when combined with the significant differences in CNV of ZNF280AY across cattle breeds, we believe that the highly variable CN of this gene is most likely due to frequent gene conversion within the ~80 palindrome-like region.…”

Rats exhibit age-related mosaic loss of chromosome Y

“…However, to date, LOY remains understudied in non-human species. In blood samples obtained from 25 bulls for over 30 months, copy number variations in the Y-linked TSPY gene have been found to both increase and decrease with age 33 . Moreover, by studying eight old mice, aneuploidies of chromosomes 7, 8, and Y were found to accumulate with age in the cerebral cortex using in situ hybridization and flow cytometric analysis and sorting (FACS) 34 .…”