We examined the relationship between gene duplication, alternative splicing, and connectedness in a predicted genetic interaction network using published data from the nematode worm Caenorhabditis elegans. Similar to previous results from mammals, genes belonging to families with only one member ("singletons") were significantly more likely to lack alternative splicing than were members of large multi-gene families. Genes belonging to multi-gene families lacking alternative splicing tended to have higher connectedness in the genetic interaction network than did genes in families that included one or more alternatively spliced members. Moreover, alternatively spliced genes were significantly more likely to interact with other alternatively spliced genes. These results support the hypothesis that certain key proteins with high degrees of network connectedness are subject to selection opposing the occurrence of alternatively spliced forms.