Think of a world populated only by giant insects on the land, and fishes in the water. According to Joost Woltering of University of Geneva, that is what Earth would look like if the transition from fins to limbs had not happened and early vertebrates had not colonised land 350 million years ago.

In a study published this week in PLoS Biology, Woltering and colleagues have found some definitive clues about this transition. By studying a group of ‘architect’ genes present in both fish and mammals – the Hox genes – the scientists were able to find out that the DNA structure and regulatory mechanism for limb and digit formation was present in fish even before the transition happened, but the enhancements required to activate digit formation evolved only in tetrapods (ie. four-legged land animals).

The role of Hox genes in limb and fin formation is crucial. Malfunctioning Hox genes result in animals missing large segments of their limbs. Mammalian Hox genes have an interesting feature. “In the forming limbs the HoxA and HoxD genes are switched on in two independent ‘waves’ the first making the proximal limb (arm/leg) and the second making the digits,” said Woltering in an email to this correspondent.

Limb formation in tetrapods is usually attributed to this ‘bimodal’ behaviour of Hox genes. So the scientists were surprised to observe the same mechanism in Hox genes in zebrafish fin radials (the bony part at the end of fins), too. So are the two structures ancestrally the same or “homologous” structures?

To test this, the team inserted fish Hox genes into mouse embryos and found that in the resulting mice, Hox genes were active only in the proximal part of the limbs, not in the digits. “This showed that the fish counterpart of the mouse ‘digit’ domain cannot yet ‘make’ digits,” said Woltering. Therefore fish fin radials and tetrapod digits are not “homologous” in the classical sense.

However, keeping in mind the shared regulatory mechanism in Hox genes of fish and those of mice, the team propose the re-definition of “homology” to go beyond common expression patterns. “For instance there are genes that are expressed in the hand and in hair follicles, this fact doesn’t make them homologous structures,” said Woltering. “Only if the underlying ‘switches’ that determine where a gene is expressed are homologous, the structures are homologous.”

Dr. Arkhat Abzhanov, an evolutionary biologist from Harvard University who was not involved in the study, agrees. “Identical expression patterns of the same gene(s) could in principle be established by non-homologous regulatory mechanisms so it might be very helpful to look at the regulatory details,” he said in an email.

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