Conservation of linkage and evolution of developmental function within the Tbx2/3/4/5 subfamily of T-box genes: implications for the origin of vertebrate limbs.
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.
Horton
Amy C
AC
Department of Biology, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, USA.
Mahadevan
Navin R
NR
Minguillon
Carolina
C
Osoegawa
Kazutoyo
K
Rokhsar
Daniel S
DS
Ruvinsky
Ilya
I
de Jong
Pieter J
PJ
Logan
Malcolm P
MP
Gibson-Brown
Jeremy J
JJ
D000818:Animals; D002816:Chordata, Nonvertebrate / Q000196:embryology* / Q000235:genetics*; D019143:Evolution, Molecular; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D020825:T-Box Domain Proteins / Q000235:genetics*; D014714:Vertebrates / Q000196:embryology / Q000235:genetics
C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5