Cheng Han Hua, Ying Ming, Tian Yi Hao, Guo Yiqing, McElreavey Ken, Zhou Rong Jia
Department of Genetics and Center for Developmental Biology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Cell Res. 2006 Apr;16(4):389-93. doi: 10.1038/sj.cr.7310050.
Recent advances in the evolutionary genetics of sex determination indicate that the only molecular similarity in sex determination found so far among phyla is between the fly doublesex, worm mab-3 and vertebrate DMRT1(dsx- and mab3-related transcription factor 1) /DMY genes. Each of these factors encodes a zinc-finger-like DNA-binding motif, DM domain. Insights into the evolution and functions of human DMRT1 gene could reveal evolutionary mechanisms of sexual development. Here we report the identification and characterization of multiple isoforms of human DMRT1 in the testis. These transcripts encode predicted proteins with 373, 275 and 175 amino acids and they were generated by alternative splicing at 3' region. Expression level of DMRT1a is higher than those of both DMRT1b and c, and the DMRT1c expression was the lowest in testis, based on comparisons of mean values from real-time fluorescent quantitative RT-PCR analysis. Both DMRT1b and c result from exonization of intronic sequences, including the exonization of an Alu element. A further search for Alu elements within the DMRT1 gene demonstrated that all 99 Alu elements are non-randomly distributed among the non-coding regions on both directions. These new characteristics of DMRT1 would have an important impact on the evolution of sexual development mechanisms.
性别决定进化遗传学的最新进展表明，到目前为止在各门类中发现的性别决定方面唯一的分子相似性存在于果蝇的双性基因、线虫的mab-3基因以及脊椎动物的DMRT1（双性和mab3相关转录因子1）/DMY基因之间。这些因子各自编码一种锌指样DNA结合基序，即DM结构域。深入了解人类DMRT1基因的进化和功能可能会揭示性发育的进化机制。在此，我们报告了人类睾丸中DMRT1多种异构体的鉴定与特征分析。这些转录本编码预测的含373、275和175个氨基酸的蛋白质，它们是由3'区域的可变剪接产生的。基于实时荧光定量逆转录聚合酶链反应分析的平均值比较，DMRT1a的表达水平高于DMRT1b和c，且DMRT1c在睾丸中的表达最低。DMRT1b和c均由内含子序列的外显子化产生，包括一个Alu元件的外显子化。对DMRT1基因内Alu元件的进一步搜索表明，所有99个Alu元件在两个方向的非编码区域中均呈非随机分布。DMRT1的这些新特征将对性发育机制的进化产生重要影响。
