A conserved developmental patterning network produces quantitatively different output in multiple species of Drosophila.
A conserved developmental patterning network produces quantitatively different output in multiple species of Drosophila.
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DOI：
10.1371/journal.pgen.1002346
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发表时间：
2011-10
期刊：
影响因子：
4.5
通讯作者：
DePace AH
中科院分区：
文献类型：
--
作者：
Fowlkes CC;Eckenrode KB;Bragdon MD;Meyer M;Wunderlich Z;Simirenko L;Luengo Hendriks CL;Keränen SV;Henriquez C;Knowles DW;Biggin MD;Eisen MB;DePace AH
基因表达的水平、时间或位置的差异可以在分子和生物体水平上促成替代表型。理解表达差异的起源是复杂的，因为生物体形态和基因调控网络甚至在密切相关的物种之间也可能存在差异。为了评估这种变化的范围，我们使用高分辨率成像方法来测量果蝇yakuba和果蝇pseudobscura胚盘胚胎中的mRNA表达，并将这些数据组装成细胞分辨率图谱，其中分割网络中13个基因的表达水平平均为物种特异性细胞分辨率形态框架。我们证明，这些物种的胚盘胚胎在其形态的大小，形状和核数方面有所不同。我们提出了一种方法来比较物种之间的细胞基因表达模式，同时考虑不同的胚胎形态，并将其应用到我们的数据和果蝇的等效数据集。我们的分析表明，所有的个体基因在这些物种之间的时空表达模式上存在数量上的差异，主要是在它们的相对位置和动态方面。尽管有许多小的数量差异，细胞基因表达谱的基因检查的整个集合在很大程度上是相似的。这表明在这个发育阶段的细胞类型是保守的，尽管它们在相对位置上可以相差多达3-4个细胞宽度，在物种之间的相对比例上可以相差多达5倍。相应细胞类型之间基因子集的动态和相对水平的定量差异可能反映了物种之间调节功能的改变。我们的研究结果强调，转录网络可以在很短的进化时间尺度上分化，即使是很小的变化也可以导致不同的输出在等效细胞的位置和数量方面。一个基因要正常发挥功能，它必须在正确的地方、正确的时间和正确的数量上发挥作用。任何这些特征的变化都可能导致个体和物种之间的明显差异，在某些情况下可能导致疾病。我们目前还不了解基因表达的位置、时间和数量是如何在DNA序列中编码的。解决这个问题的一种方法是比较不同物种之间基因表达的差异，并试图将DNA序列的变化与基因表达的变化联系起来。在这里，我们采取的第一步，通过比较基因表达模式在高空间和时间分辨率的三种果蝇胚胎之间。我们开发了比较单个细胞中基因表达的方法，这使我们能够控制胚胎之间细胞核大小，形状和数量的变化。我们发现，在我们检查过的所有单个基因的模式中，都存在可测量的数量差异。然而，通过同时考虑我们数据集中的所有基因，我们发现许多基因都在一起变化，导致这三个物种中的细胞类型基本相同。
Differences in the level, timing, or location of gene expression can contribute to alternative phenotypes at the molecular and organismal level. Understanding the origins of expression differences is complicated by the fact that organismal morphology and gene regulatory networks could potentially vary even between closely related species. To assess the scope of such changes, we used high-resolution imaging methods to measure mRNA expression in blastoderm embryos of Drosophila yakuba and Drosophila pseudoobscura and assembled these data into cellular resolution atlases, where expression levels for 13 genes in the segmentation network are averaged into species-specific, cellular resolution morphological frameworks. We demonstrate that the blastoderm embryos of these species differ in their morphology in terms of size, shape, and number of nuclei. We present an approach to compare cellular gene expression patterns between species, while accounting for varying embryo morphology, and apply it to our data and an equivalent dataset for Drosophila melanogaster. Our analysis reveals that all individual genes differ quantitatively in their spatio-temporal expression patterns between these species, primarily in terms of their relative position and dynamics. Despite many small quantitative differences, cellular gene expression profiles for the whole set of genes examined are largely similar. This suggests that cell types at this stage of development are conserved, though they can differ in their relative position by up to 3–4 cell widths and in their relative proportion between species by as much as 5-fold. Quantitative differences in the dynamics and relative level of a subset of genes between corresponding cell types may reflect altered regulatory functions between species. Our results emphasize that transcriptional networks can diverge over short evolutionary timescales and that even small changes can lead to distinct output in terms of the placement and number of equivalent cells. For a gene to function properly, it must be active in the right place, at the right time, and in the right amount. Changes in any of these features can lead to observable differences between individuals and species and in some cases can lead to disease. We do not currently understand how the position, timing, and amount of gene expression is encoded in DNA sequence. One approach to this problem is to compare how gene expression differs between species and to try to relate changes in DNA sequence to changes in gene expression. Here, we take the first step by comparing gene expression patterns at high spatial and temporal resolution between embryos of three species of fruit flies. We develop methods for comparing gene expression in individual cells, which allow us to control for variation in the size, shape, and number of nuclei between embryos. We find measurable quantitative differences in the patterns for all individual genes that we have examined. However, by considering all genes in our dataset at once, we show that many genes are changing together, leading to largely equivalent types of cells in these three species.
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