Evolution of Dosage Compensation - An Empirical Test using Turtles with Independently Evolved XX/XY and ZZ/ZW Chromosomes

剂量补偿的演变 - 使用具有独立进化 XX/XY 和 ZZ/ZW 染色体的海龟进行的实证测试

• 批准号: 1555999
• 负责人: Nicole Valenzuela
• 金额: $ 85.5万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1555999&HistoricalAwards=false
• 关键词: Evolution; Dosage; Compensation; Empirical; Test

This project will illuminate the evolution of dosage compensation (DC) by contrasting turtle species with XX/XY, ZZ/ZW and temperature-dependent (TSD) gender determination. In species like humans, XX/XY females have two copies of genes in the X chromosome and males one because females carry two Xs and males one X and one Y. An imbalance in gene dosage, such the one caused by the difference in the number of X or Z chromosomes between genders, may reduce fitness or even cause death, without a mechanism to re-establish a balance. Dosage compensation mechanisms (DCM) equalize the activity of genes located in the X or Z (X-linked or Z-linked) between chromosomes, and between males and females. DC is important for normal development, and has consequences for the evolution of genomes and speciation. Yet, DCM diversity and evolution remain unclear. Turtles are ideal to study DCM evolution because XX/XY and ZZ/ZW chromosomes have evolved independently multiple times, and there are increasing turtle genomic resources. To address this puzzle, gene expression is being compared in turtles with contrasting mechanisms of gender determination. The results will advance our understanding of the diversity and evolution of DMC by illuminating whether there are general rules to DCM across organisms or whether unique solutions evolved independently in each lineage. This project involves undergraduate discovery-based learning by recruiting biology undergraduates, and broadens the participation of underrepresented groups in biology. Undergraduates will be trained in a variety of biological fields, participate in reflection sessions and present their results at scientific meetings. Results will be disseminated via presentations, publications, and a bilingual web-site. When XX/XY or ZZ/ZW chromosomes evolve in diploid species, genes are lost from the Y or W (or lose their function) as they degenerate over time due to their lower recombination. This loss means that XY-males carry a single functional copy of X-genes while XX-females carry two copies (likewise, ZW females have one copy of Z-genes and ZZ-males have two copies). Because X- and Z-linked genes are part of genetic networks, the inequality of gene copy number causes an imbalance in transcription which may produce sub-optimal or lethal phenotypes, unless a mechanism existed to re-establish a balance. In the absence of such mechanism, transcription will differ (a) between genes in these chromosomes and autosomes in XY males (or ZW females), and (b) between males and females for X-genes (or Z-genes). Dosage compensation (DC) is a system to equalize the activity of X- or Z-linked genes to counterbalance the deleterious effects of differential gene copy number. DC re-establishes a balance between these genes and autosomal genes ("chromosome-to-autosome" compensation), and between the genders ("male-to-female" compensation). Mechanisms may balance entire chromosomes (global compensation), other some genes only (local compensation). This project tests the hypothesis that global DC (i.e. chromosome-wide) does not evolve inevitably with the evolution of chromosomes, but instead that DC tends to be local when present (i.e. affecting some genes only), and independent of the size, evolutionary age, and gene content of the chromosomes. Accordingly, this project it is sequencing microdissected turtle chromosomes, and examining them by arrayCGH, and assessing the expression of these genes via transcriptomics.

该项目将通过将乌龟物种与XX/XY，ZZ/ZW和温度依赖性（TSD）性别确定来阐明剂量补偿（DC）的演变。 在像人类这样的物种中，XX/XY女性在X染色体和男性中具有两份基因，一个是因为女性携带两个XS和男性一个X和一个Y。基因剂量的不平衡，这是由于X或Z染色体的差异引起的X或Z染色体的差异可能会减少适应性甚至无法使死亡造成的机械依赖能力，而无需先有一位机械的依赖，而这可能会导致一定的生命。剂量补偿机制（DCM）均衡了位于染色体之间以及男性和女性之间的X或Z（X连锁或Z连接）的基因的活性。 DC对于正常发育很重要，并且对基因组和物种形成的进化产生了影响。然而，DCM多样性和进化尚不清楚。乌龟是研究DCM进化的理想选择，因为XX/XY和ZZ/ZW染色体多次独立进化，并且乌龟基因组资源的越来越多。为了解决这个难题，正在比较乌龟中的基因表达，并与性别确定的对比机制进行了比较。 结果将通过阐明跨生物体是否有DCM的一般规则，或者独特的解决方案是否在每个谱系中独立进化，从而提高我们对DMC多样性和演变的理解。该项目涉及通过招募生物学大学生的本科生学习，并扩大了代表性不足的群体在生物学中的参与。本科生将接受各种生物学领域的培训，参加反思会议，并在科学会议上介绍其结果。结果将通过演示，出版物和双语网站传播。当XX/XY或ZZ/ZW染色体在二倍体物种中进化时，由于其较低的重组而随着时间的流逝而退化，因此基因因Y或W（或失去功能）而丢失。这种损失意味着XY-males携带X-Genes的单个功能副本，而XX-Females携带两个副本（同样，ZW女性具有一个Z-Genes和ZZ-Males的副本，有两个副本）。由于X和Z连接的基因是遗传网络的一部分，因此基因拷贝数的不平等导致转录失衡，除非存在一种机制来重新建立平衡，否则可能会产生亚最佳或致命表型。 在没有这种机制的情况下，这些染色体中的基因和XY雄性（或ZW女性）的常染色体之间的转录将有所不同，并且（b）X-Genes（或Z-Genes）的男性和雌性之间的转录会有所不同。剂量补偿（DC）是一个均衡X-或Z连锁基因活性以抵消差异基因拷贝数的有害作用的系统。 DC重新建立了这些基因和常染色体基因（“染色体至自动体”补偿）和性别之间的平衡（“男性到女性”补偿）。机制可以平衡整个染色体（全球补偿），仅其他一些基因（局部补偿）。该项目检验了以下假设：随着染色体的演变，全球DC（即全染色体）不可避免地进化，而是在存在时DC倾向于局部（即仅影响某些基因），并且与染色体的大小，进化年龄和基因含量无关。 因此，该项目正在测序微解剖的乌龟染色体，并通过Arraycgh检查它们，并通过转录组学评估这些基因的表达。