T-box genes encode a family of DNA-binding transcription factors implicated in numerous developmental processes in all metazoans. The Tbx2/3/4/5 subfamily genes are especially interesting because of their key roles in the evolution of vertebrate appendages, eyes, and the heart, and, like the Hox genes, the longevity of their chromosomal linkage. A BAC library derived from the single male amphioxus (Branchiostoma floridae) used to sequence the amphioxus genome was screened for AmphiTbx2/3 and AmphiTbx4/5, yielding two independent clones containing both genes. Using comparative expression, genomic linkage, and phylogenetic analyses, we have reconstructed the evolutionary histories of these members of the T-box gene family. We find that the Tbx2-Tbx4 and Tbx3-Tbx5 gene pairs have maintained tight linkage in most animal lineages since their birth by tandem duplication, long before the divergence of protostomes and deuterostomes (e.g., arthropods and vertebrates) at least 600 million years ago, and possibly before the divergence of poriferans and cnidarians (e.g., sponges and jellyfish). Interestingly, we find that the gene linkage detected in all vertebrate genomes has been maintained in the primitively appendage-lacking, basal chordate, amphioxus. Although all four genes have been involved in the evolution of developmental programs regulating paired fin and (later) limb outgrowth and patterning, and most are also implicated in eye and heart development, linkage maintenance--often considered due to regulatory constraints imposed by limb, eye, and/or heart associated gene expression--is undoubtedly a consequence of other, much more ancient functional constraints.

中文翻译：

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T-box 基因 Tbx2/3/4/5 亚家族内发育功能的连锁和进化的保守性：对脊椎动物肢体起源的影响。

T-box 基因编码一个与所有后生动物的许多发育过程有关的 DNA 结合转录因子家族。Tbx2/3/4/5 亚家族基因特别有趣，因为它们在脊椎动物附肢、眼睛和心脏的进化中起关键作用，并且与 Hox 基因一样，它们的染色体连锁的寿命也很长。从用于测序文昌鱼基因组的单个雄性文昌鱼 (Branchiostoma floridae) 衍生的 BAC 文库筛选了 AmphiTbx2/3 和 AmphiTbx4/5，产生了两个包含这两个基因的独立克隆。使用比较表达、基因组联系和系统发育分析，我们重建了 T-box 基因家族这些成员的进化历史。我们发现 Tbx2-Tbx4 和 Tbx3-Tbx5 基因对在大多数动物谱系中自出生以来就通过串联复制保持紧密联系，早在至少 6 亿年前原生动物和后口动物（例如节肢动物和脊椎动物）的分歧之前，并且可能在多孔动物和刺胞动物（例如海绵和水母）的分化之前。有趣的是，我们发现在所有脊椎动物基因组中检测到的基因连锁一直保持在原始缺乏附属物的基础脊索动物文昌鱼中。尽管所有四个基因都参与了调节成对鳍和（后来的）肢体生长和模式的发育程序的进化，并且大多数还与眼睛和心脏发育有关，但由于肢体施加的监管限制，通常被认为是联系维持，眼睛，