The Genomic Organization and Gene Repertoire of the Male-specific Region of the Bovine Y Chromosome
Open Access
- Author:
- Chang, Ti-Cheng
- Graduate Program:
- Integrative Biosciences
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- February 09, 2012
- Committee Members:
- Wansheng Liu, Dissertation Advisor/Co-Advisor
Wansheng Liu, Committee Chair/Co-Chair
Cooduvalli S Shashikant, Committee Member
Kateryna Dmytrivna Makova, Committee Member
Stephen Wade Schaeffer, Committee Member - Keywords:
- Y chromosome
Gene transposition
Transcriptome
Natural selection
Spermatogenesis
Lineage-specific gene family - Abstract:
- The male-specific region of the mammalian Y chromosome (MSY) was evolved as a consequence of the progressive differentiation of sex chromosomes. During evolution, different lineages acquired and retained distinct sets of lineage-specific Y genes in the MSY due to the independent Y chromosome decay and chromosome rearrangements. However, the knowledge about the gene content and genomic organization of the Y chromosome is still limited. The major reason is the enrichment of repetitive sequences in the Y chromosome that has impeded Y chromosome sequencing and further characterization of Y-linked genes. Therefore, this dissertation targeted at expanding our knowledge on mammalian Y chromosome through identifying and characterizing the bovine (Bos taurus) MSY transcriptome and investigating the genomic organization of the bovine MSY. The bovine MSY contains three major regions: X-degenerate (Xd), Y-ampliconic (Ya), and Y-transitional (Yt). Xd splits into two regions (Xd1& Xd2) located at either end of MSY, spanning 2.4 Mb. Xd1 comprises ten single-copy genes (EIF1AY, AMELY, OFD1Y, USP9Y, ZRSR2Y, UTY, DDX3Y, RPL23AY, ZFY, and EIF2S3Y), two of which (ZRSR2Y & RPL23Y) are bovid-specific; Xd2 harbors two genes (SRY and RBMY). Ya spans 34.8 Mb, a majority of which (68.6%) shares intra-chromosomal similarities ≥99%. Distinct from the human ampliconic region, the bovine Ya is organized into a higher ordered repeat structure with an array of inverted repeats containing four major gene families (ZNF280BY, ZNF280AY, TSPY-M2, and HSFY) with copy numbers ranging from ~80 to 230. ZNF280BY and ZNF280AY are bovid-specific. Each inverted repeat (~420 Kb) represents a repeat unit, which is repeated up to ~80 times. Yt (~3.3 Mb) is located between Xd1 and Ya, with a transitional sequence feature between Xd and Ya, where a bovid-specific gene family (PRAMEY, 10 copies) are present. In addition, ~400 novel transcription units (TUs) were identified. The majority of the examined ampliconic gene families (12/14) are predominantly expressed in testis, suggesting a role in spermatogenesis. Furthermore, antisense transcription of ZNF280BY and PRAMEY was detected in spermatids, indicating that the antisense RNA may participate in coordinated gene regulations in testis. The ampliconic ZNF280BY, ZNF280AY and PRAMEY gene families were derived from the transposition of a gene block on the bovine chromosome 17. At least two major genomic expansions of the ampliconic region have been observed, which are likely associated with adaptation and speciation of the bovid lineages. Further analyses were performed for two X-degenerate genes, DDX3Y and OFD1Y. The DDX3Y gene, comprising a DEAD motif, belongs to the DEAD-box polypeptide 3 (DDX3) subfamily with a main role in RNA metabolism. In addition to the sex chromosome-linked DDX3X and DDX3Y, autosomal homologs, named PL10, were present in mammals. Pseudogenized homologs are also present on the autosomes and mammalian X Chr, which were derived from lineage-specific retropositions. The autosomal retroposed homologs may still be active transcriptionally as demonstrated in the bovine. The OFD1Y gene is another X-degenerate gene in the bovine MSY. The ortholog of this gene on the human X chromosome has been implicated in several developmental disorders. The bovine OFD1Y was identified from the MSY transcriptome and expressed differentially from the bovine OFD1X. Comparison of OFD1Y and neighboring genes against their X-linked paralogs indicated that the expansion of the ampliconic region may initiate from the X-degenerated sequence. Furthermore, different regions of OFD1/OFD1X/OFD1Y are subject to differential selection pressures, which appears to be associated with diverse syndromes derived from the OFD1 mutations. The identified bovine MSY transcriptome serves as an important resource for studying Y-linked genetic factors involved in male-specific function. Further understandings of how these genes function in bovine will offer insights into their roles or related biological processes in the other species.