Molecular evolution of the moonlighting protein SMN in metazoans

Abstract

The spinal muscular atrophy (SMA) associated protein survival of motor neuron (SMN) is known to be a moonlighting protein: having one primary, ancestral function (presumed to be involvement in U snRNP assembly) along with one or more secondary functions. One hypothesis for the evolution of moonlighting proteins is that regions of a structure under relatively weak negative selection could gain new functions without interfering with the primary function. To test this hypothesis, we investigated sequence conservation and dN/dS, which reflects the selection acting on a coding sequence, in SMN and a related protein, splicing factor 30 (SPF30), which is not currently known to be multifunctional. We found very different patterns of evolution in the two genes, with SPF30 characterized by strong sequence conservation and negative selection in most animal taxa investigated, and SMN with much lower sequence conservation, and much weaker negative selection at many sites. Evidence was found of positive selection acting on some sites in primate genes for SMN. SMN was also found to have been duplicated in a number of species, and with patterns that indicate reduced negative selection following some of these duplications. There were also several animal species lacking an SMN gene.

Keywords: Moonlighting protein; SMA; SMN; SPF30; Spinal muscular atrophy; dN/dS; heterogenous nuclear ribonucleoprotein; hnRNP; small nuclear ribonucleoprotein; snRNP; spinal muscular atrophy; splicing factor 30; survival of motor neuron.