(Non)Parallel developmental mechanisms in vertebrate appendage reduction and loss

Abstract

Appendages have been reduced or lost hundreds of times during vertebrate evolution. This phenotypic convergence may be underlain by shared or different molecular mechanisms in distantly related vertebrate clades. To investigate, we reviewed the developmental and evolutionary literature of appendage reduction and loss in more than a dozen vertebrate genera from fish to mammals. We found that appendage reduction and loss was nearly always driven by modified gene expression as opposed to changes in coding sequences. Moreover, expression of the same genes was repeatedly modified across vertebrate taxa. However, the specific mechanisms by which expression was modified were rarely shared. The multiple routes to appendage reduction and loss suggest that adaptive loss of function phenotypes might arise routinely through changes in expression of key developmental genes.

Attempting genetic inference from directional asymmetry during convergent hindlimb reduction in squamates

“…In conclusion, the limited evidence for use of altered Pitx1 expression in hindlimb reduced squamates may result from the absence of the hindlimb‐specific enhancer, PelA , small effects of PelB , or the adverse pleiotropic effects of a disrupted Pen enhancer. Our findings are consistent with available evidence from non‐model organisms that there are multiple developmental and molecular routes to hindlimb reduction (Roscito et al, 2022; Swank et al, 2021). Consequently, hindlimb loss is likely non‐parallel in squamates and Pitx1 is only one of the several genetic pathways that could be used to respond to similar selection pressures.…”

“…Moreover, a recent comparative genomics study of three limb‐reduced reptile lineages found that the molecular basis of limb loss was not convergent and in no lineage was Pitx1 a major driver (Roscito et al, 2022). In this study, we corroborate the findings of Swank et al (2021) and Roscito et al (2022) with new data collected from six lizard clades that independently evolved hindlimb reduction. We tested for Pitx1 ’s signature of left‐larger asymmetry in vestigial hindlimbs and found left‐larger asymmetry in only one species.…”

“…How, then, have manatees evolved left‐biased asymmetry in their pelvic vestiges (Shapiro et al, 2006)? Indeed, it was this observation that motivated the current study and Swank et al (2021)—if manatees and stickleback have left‐biased pelvic asymmetry, might that pattern hold across more vertebrates? Apparently, it does not, or at least other genes are more important in squamates.…”

“…While this suggests the possible use of Pitx1 in Chalcides (and might warrant further phylogenetic analysis of limb reduction across skinks), it is hardly resounding evidence for the repeated use of Pitx1 in squamates. Indeed, Pitx1 does not appear to be used within Hemiergis , a different genus of skinks in which expression of another transcription factor, Sonic Hedgehog , has been implicated in digit reduction (Shapiro et al, 2003; Swank et al, 2021).…”

“…Nevertheless, a recent review of molecular and developmental evidence from multiple clades of non‐model vertebrates with hind appendage reduction found that Pitx1 use appears to be limited to sticklebacks and manatees (Swank et al, 2021). Moreover, a recent comparative genomics study of three limb‐reduced reptile lineages found that the molecular basis of limb loss was not convergent and in no lineage was Pitx1 a major driver (Roscito et al, 2022).…”