Bovine and Mouse SLO3 K+ Channels: Many Functional Differences Map to the Same Region

Abstract

Genes pertaining to male reproduction, especially those involved in sperm production, morphologically and functionally evolve much faster than their non-sexual counterparts. SLO3 is an especially intriguing example of such a rapidly evolving gene. The SLO3 gene encodes a K+ channel which is expressed only in mammalian sperm and is evolving much faster than its close paralogue SLO1 which is expressed in brain and other organs. We cloned the bovine orthologue of SLO3 (bSLO3) and compared its primary sequence and functional properties to its mouse orthologue (mSLO3) which we previously cloned. A comparison of bSLO3 and mSLO3 primary sequences showed far less conservation than for SLO1 proteins in mouse and bovine species. Functionally, bSLO3 and mSLO3 also differ markedly with respect to their voltage range of activation, their ion selectivity, and their activation kinetics. Remarkably, although there are many regions of low conservation between bSLO3 and mSLO3 proteins, we found that all of the different functional properties that we measured map to a small region of low conservation in the RCK1 domain. One or more of these different functional properties may reflect differences in the resting membrane potentials of sperm in bovine and mouse species. This work was supported by National Institute of Health grants 1R21HD056444-01A1 to C.M.S. and R24 RR017342-01 and R01 GM067154-01A1 to L.S.