Evolution of Sexually Dimorphic Germ Cells in Volvox carteri

描述（由申请人提供）：摘要。这项工作的长期目标是了解发育复杂性背后的分子遗传机制。在生命的历史上，多细胞生物已经进化了多次，并导致了真核生物多样性的爆炸，包括新的生殖策略。两性异形和多细胞性在几个谱系中共同进化，但导致它们在动物和植物中共同进化的机制存在于遥远的过去，并且未知。团藻是一种多细胞绿色藻类，与其最近的单细胞亲戚莱茵衣藻有着共同的祖先。卡特氏弧菌从单细胞衣原体祖先进化出许多后生动物的特征，包括完全的生殖体分离和性二态发育。在性分化过程中，卡特氏弧菌雌性产生卵子，雄性产生精子，这是由具有两个等位基因的交配型（mt）基因座控制的性状，mtf（雌性）和mtm（雄性）。编码卡特弧菌mt的基因组区域已被鉴定并部分表征，导致以下目的：（i）mt的两个等位基因的克隆和测序;（ii）使用注释和转录谱分析来鉴定性别决定的关键调控因子;（iii）表征负责性二态发育的基因，包括vMATS，一种线粒体连锁的视网膜母细胞瘤（RB）肿瘤抑制基因同源物，在卡特氏弧菌雄性和雌性之间具有高度多态性;（四）通过使用异位表达和遗传学方法直接测试雌性和雄性vMATS同种型和其他潜在的性别决定基因在调节性分化中的作用，灭活实验。卡特氏弧菌交配位点的发现提供了一个前所未有的机会来剖析性二型性进化背后的分子遗传变化，并了解性染色体如何进化以影响发育编程。本案无关生殖细胞对人类生殖健康至关重要，也与某些形式的人类癌症有关，但对其生物学知之甚少。本文提出的工作有望揭示导致在简单模型系统中产生卵子和精子的潜在遗传结构，并且已经揭示了人类肿瘤抑制因子和生殖细胞形成之间的潜在保守联系。

DESCRIPTION (provided by applicant): SUMMARY. The long-term goal of this work is to understand the molecular genetic mechanisms that underlie developmental complexity. Multicellularity has evolved multiple times in the history of life and has led to an explosion of eukaryotic diversity, including novel reproductive strategies. Sexual dimorphism and multicellularity have coevolved in several lineages, but the mechanisms that led to their co-evolution in animals and plants lie in the distant past and are unknown. Volvox carteri is a multicellular green alga that shares recent common ancestry with its closest unicellular relative, Chlamydomonas reinhardtii. From a single-celled Chlamydomonas ancestor V. carteri has evolved many metazoan-like features including complete germ-soma separation and sexually dimorphic development. During sexual differentiation V. carteri females produce eggs and males produce sperm, a trait that is controlled by a mating type (mt) locus with two alleles, mtf (female) and mtm (male). The genomic region that encodes V. carteri mt has been identified and partially characterized, leading to the following Aims: (i) Clone and sequence both alleles of mt; (ii) Use annotation and transcriptional profiling to identify key regulators of sex determination; (iii) Characterize the genes that are responsible for sexually dimorphic development including vMATS, a mt-linked retinoblastoma (RB) tumor suppressor homolog that is highly polymorphic between V. carteri males and females; (iv) Directly test the role of female and male vMATS isoforms and other potential sex determining genes in regulating sexual differentiation by using ectopic expression and genetic inactivation experiments. The discovery of the V. carteri mating locus provides an unprecedented opportunity to dissect the molecular genetic changes that underlie the evolution of sexual dimorphism and to understand how sex chromosomes evolve to influence developmental programming. RELEVANCE. Germ cells are critical for human reproductive health and are also associated with some forms of human cancer, but their biology is poorly understood. The work proposed here is expected to reveal the underlying genetic architecture that leads to the production of eggs and sperm in a simple model system, and has already uncovered a potentially conserved link between a human tumor suppressor and germ cell formation.