Tomaszkiewicz Marta, Sahlin Kristoffer, Medvedev Paul, Makova Kateryna D
Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA.
Department of Mathematics, Science for Life Laboratory, Stockholm University, 106 91, Stockholm, Sweden.
bioRxiv. 2023 Mar 18:2023.03.02.530874. doi: 10.1101/2023.03.02.530874.
Y-chromosomal Ampliconic Genes (YAGs) are important for male fertility, as they encode proteins functioning in spermatogenesis. The variation in copy number and expression levels of these multicopy gene families has been recently studied in great apes, however, the diversity of splicing variants remains unexplored. Here we deciphered the sequences of polyadenylated transcripts of all nine YAG families (, , , , , , , , and ) from testis samples of six great ape species (human, chimpanzee, bonobo, gorilla, Bornean orangutan, and Sumatran orangutan). To achieve this, we enriched YAG transcripts with capture-probe hybridization and sequenced them with long (Pacific Biosciences) reads. Our analysis of this dataset resulted in several findings. First, we uncovered a high diversity of YAG transcripts across great apes. Second, we observed evolutionarily conserved alternative splicing patterns for most YAG families except for and . Our results suggest that transcripts and predicted proteins in several great ape species (bonobo and the two orangutans) have independent evolutionary origins and are not homologous to human reference transcripts and proteins. In contrast, our results suggest that the gene family, having the highest representation of transcripts without open reading frames, has been undergoing pseudogenization. Third, even though we have identified many species-specific protein-coding YAG transcripts, we have not detected any signatures of positive selection. Overall, our work illuminates the YAG isoform landscape and its evolutionary history, and provides a genomic resource for future functional studies focusing on infertility phenotypes in humans and critically endangered great apes.
Y染色体扩增基因（YAGs）对男性生育能力很重要，因为它们编码在精子发生过程中发挥作用的蛋白质。最近在大猩猩中研究了这些多拷贝基因家族的拷贝数和表达水平的变化，然而，剪接变体的多样性仍未得到探索。在这里，我们破译了来自六种大猩猩物种（人类、黑猩猩、倭黑猩猩、大猩猩、婆罗洲猩猩和苏门答腊猩猩）睾丸样本中所有九个YAG家族（、、、、、、、和）的多聚腺苷酸化转录本的序列。为了实现这一目标，我们通过捕获探针杂交富集YAG转录本，并用长读长（太平洋生物科学公司）进行测序。我们对该数据集的分析得出了几个发现。首先，我们发现大猩猩中YAG转录本具有高度多样性。其次，除了和外，我们观察到大多数YAG家族在进化上保守的可变剪接模式。我们的结果表明，几种大猩猩物种（倭黑猩猩和两种猩猩）中的转录本和预测蛋白质具有独立的进化起源，与人类参考转录本和蛋白质不同源。相比之下，我们的结果表明，基因家族中没有开放阅读框的转录本比例最高，一直在经历假基因化。第三，尽管我们已经鉴定出许多物种特异性的蛋白质编码YAG转录本，但我们没有检测到任何正选择的特征。总体而言，我们的工作阐明了YAG异构体的情况及其进化历史，并为未来关注人类和极度濒危大猩猩不育表型的功能研究提供了基因组资源。
