Ottolenghi Chris, Fellous Marc, Barbieri Marcello, McElreavey Ken
Immunogénétique Humaine, INSERM E0021, Institut Pasteur, 25 rue du Dr Roux, Paris Cedex 15, 75724, France.
Genomics. 2002 Mar;79(3):333-43. doi: 10.1006/geno.2002.6711.
Recent advances in the evolutionary genetics of sex determination indicate that DMRT1 may be a vertebrate equivalent of the Drosophila melanogaster master sex regulator gene, doublesex. The role of DMRT1 seems to be confined to some aspects of male sex differentiation, whereas in Drosophila, doublesex has wider developmental effects in both sexes. This suggests other homologs of doublesex may exist in the vertebrate genome and encode sex-specific functions not displayed by DMRT1. We identified and characterized five novel human DM genes, distinct from previously described family members. Human DM genes map to three well-defined regions of chromosomes 1, 9, and 19 (one gene on chromosome 19 having an additional homolog on chromosome X). We collated data indicating these chromosomal regions harbor multiple syntenic genes sharing highly specific paralogy relations, suggesting that they arose early during vertebrate evolution. The 9p21-p24.3 bands represent the ancestral copy and harbor closely linked DM genes that may reflect the overall diversity of the fruit fly DM gene family. The human genome contains a small number of potential doublesex homologs that may be involved in human sexual development. Identifying highly conserved chromosomal regions, such as distal 9p, is an important tool to trace complex ancient evolutionary processes inaccessible by other approaches.
性别决定进化遗传学的最新进展表明，DMRT1可能相当于果蝇的主要性别调节基因双性基因（doublesex）在脊椎动物中的对应物。DMRT1的作用似乎局限于雄性性别分化的某些方面，而在果蝇中，双性基因在两性中具有更广泛的发育影响。这表明双性基因的其他同源物可能存在于脊椎动物基因组中，并编码DMRT1未表现出的性别特异性功能。我们鉴定并表征了五个新的人类DM基因，它们不同于先前描述的家族成员。人类DM基因定位于染色体1、9和19的三个明确区域（染色体19上的一个基因在X染色体上有一个额外的同源物）。我们整理的数据表明，这些染色体区域含有多个具有高度特异性旁系同源关系的同线基因，这表明它们在脊椎动物进化早期就已出现。9p21 - p24.3带代表祖先拷贝，并含有紧密连锁的DM基因，这可能反映了果蝇DM基因家族的整体多样性。人类基因组包含少量可能参与人类性发育的潜在双性基因同源物。识别高度保守的染色体区域，如9p远端，是追踪其他方法无法触及的复杂古老进化过程的重要工具。
