Copy number variation in intron 1 of SOX5 causes the Pea-comb phenotype in chickens.
Copy number variation in intron 1 of SOX5 causes the Pea-comb phenotype in chickens.
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DOI：
10.1371/journal.pgen.1000512
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发表时间：
2009-06
期刊：
影响因子：
4.5
通讯作者：
Andersson L
中科院分区：
文献类型：
--
作者：
Wright D;Boije H;Meadows JR;Bed'hom B;Gourichon D;Vieaud A;Tixier-Boichard M;Rubin CJ;Imsland F;Hallböök F;Andersson L
豌豆梳是鸡的显性突变，它大大减少了鸡冠和肉垂的大小。这是一种适应寒冷气候的特性，因为它减少了热量损失，使鸡不易受霜冻的影响。在这里，我们报告，豌豆梳是由位于附近的进化保守的非编码序列的编码SOX 5转录因子的基因的内含子1的重复序列的大规模扩增。这一定是致病突变，因为所有其他多态性与豌豆梳等位基因被排除的遗传分析。S0X5控制细胞命运和分化，并且对于骨骼发育、软骨细胞分化和细胞外基质产生是必需的。早期胚胎中的免疫染色表明，豌豆梳与位于表面外胚层下方的间充质细胞中SOX 5的异位表达相关，其中梳子和垂肉随后将发育。结果表明，重复扩增干扰调控SOX 5的表达过程中的细胞分化的梳子和垂的发展至关重要。该研究为促进表型进化的突变本质提供了新的见解，并且是首次描述了这个对发育重要的基因中自发且完全可行的突变。无羽的鸡冠和肉垂是鸡的特征。虽然豌豆梳等位基因被认为表现出显性遗传，并大大减少了梳子和垂肉的大小，但突变背后的遗传学仍然难以捉摸。鸡冠主要由软骨细胞产生的胶原蛋白和透明质酸组成。这些细胞是在软骨形成途径中通过间充质细胞的浓缩和分化形成的，其早期阶段受SOX转录因子调节。在这里，我们查明了一个大规模扩增的重复序列在第一内含子的SOX 5作为导致豌豆梳表型。通过研究早期胚胎，我们发现SOX 5在豌豆梳动物的梳子和垂肉的细胞中的限制性发育阶段异位表达。我们假设，序列重复改变调控SOX 5的表达时，梳子和肉垂发育所必需的细胞分化正在发生。豌豆梳增加了越来越多的表型变异，这是由调节突变解释，因此证明了这些事件的进化意义。
Pea-comb is a dominant mutation in chickens that drastically reduces the size of the comb and wattles. It is an adaptive trait in cold climates as it reduces heat loss and makes the chicken less susceptible to frost lesions. Here we report that Pea-comb is caused by a massive amplification of a duplicated sequence located near evolutionary conserved non-coding sequences in intron 1 of the gene encoding the SOX5 transcription factor. This must be the causative mutation since all other polymorphisms associated with the Pea-comb allele were excluded by genetic analysis. SOX5 controls cell fate and differentiation and is essential for skeletal development, chondrocyte differentiation, and extracellular matrix production. Immunostaining in early embryos demonstrated that Pea-comb is associated with ectopic expression of SOX5 in mesenchymal cells located just beneath the surface ectoderm where the comb and wattles will subsequently develop. The results imply that the duplication expansion interferes with the regulation of SOX5 expression during the differentiation of cells crucial for the development of comb and wattles. The study provides novel insight into the nature of mutations that contribute to phenotypic evolution and is the first description of a spontaneous and fully viable mutation in this developmentally important gene. The featherless comb and wattles are defining features of the chicken. Whilst the Pea-comb allele was known to show a dominant inheritance and drastically reduce the size of both comb and wattles, the genetics underlying the mutation remained elusive. Chicken comb is primarily composed of collagen and hyaluronan, which are produced by chondrocytes. These cells are formed through the condensation and differentiation of mesenchyme cells during the chondrogenesis pathway, the early stages of which are regulated by SOX transcription factors. Here we pinpoint a massive amplification of a duplicated sequence in the first intron of SOX5 as causing the Pea-comb phenotype. By studying early embryos, we show that SOX5 is ectopically expressed during a restricted stage of development in the cells which underlie the comb and wattles of Pea-comb animals. We hypothesise that the sequence duplication alters the regulation of SOX5 expression when the differentiation of cells essential for comb and wattle development is taking place. Pea-comb adds to the growing list of phenotypic variation which is explained by regulatory mutations and so demonstrates the evolutionary significance of such events.
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影响因子：
64.8
作者：
Cook, Edwin H., Jr.;Scherer, Stephen W.
通讯作者：
Scherer, Stephen W.
黄色皮肤基因的鉴定显示了家鸡的杂种起源。
影响因子：
4.5
作者：
Eriksson, Jonas;Larson, Greger;Gunnarsson, Ulrika;Bed'hom, Bertrand;Tixier-Boichard, Michele;Stromstedt, Lina;Wright, Dominic;Jungerius, Annemieke;Vereijken, Addie;Randi, Ettore;Jensen, Per;Andersson, Leif
通讯作者：
Andersson, Leif
影响因子：
11.4
作者：
Lefebvre, V;Li, P;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
DOI：
10.1073/pnas.0806791105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Kwan, Kenneth Y.;Lam, Mandy M. S.;Sestan, Nenad
通讯作者：
Sestan, Nenad
影响因子：
--
作者：
LAWRENCE, IE
通讯作者：
LAWRENCE, IE