The evolution of the LR axis

 Our phylogenetic screen for genes that have disappeared in vertebrate species as a consequence or cause of deciliation of the LRO yielded important evolutionary insights into the developmental programs of LR specification. Indeed, all five genes (CIROP, C1orf127, MMP21, DAND5 and PKD1L1) were found here, and by others before, to be expressed in the very tissue and at the correct time to play a role in LR axis formation. These genes are not linked physically on the same chromosomal location and, as such, escape the traditional definition of an operon. However, they seem to be functionally interlocked in a transcriptionally coordinated group, which could be referred to as a ‘functional operon’ for LR patterning.

The facultative nature of this ‘evo-devo module’ is striking, since, with enough time, all of these genes were lost in reptiles and birds or have become pseudogenes in cetartiodactyla. Forming an integrated module, we suspect that, like a bidirectional domino effect, if any given gene becomes inactivated, the other four will all become obsolete too. This paradigm is of immediate importance since we note that carnivores have already begun to lose C1orf127 but still harbor what appears to be functional genes for CIROP, MMP21, DAND5 and PKD1L1. This indicates that a forfeiture of this functional module might be occurring contemporarily. If so, this should allow us to settle the corollary question of which comes first. Is it the deciliation of the LRO that triggers the obsolescence of this functional operon, or is it the loss of one of these five genes that specifically turns off the program of motile ciliogenesis within the LRO? Observing the organizer of canine or feline embryos might help us answer this egg/chicken dilemma and give evolutionary biologists the opportunity to investigate how evo-devo traits become fixed or purged in coeval vertebrate species.