Mammalian genomes contain numerous genes for long noncoding RNAs (lncRNAs). The 
functions of the lncRNAs remain largely unknown but their evolution appears to 
be constrained by purifying selection, albeit relatively weakly. To gain 
insights into the mode of evolution and the functional range of the lncRNA, they 
can be compared with much better characterized protein-coding genes. The 
evolutionary rate of the protein-coding genes shows a universal negative 
correlation with expression: highly expressed genes are on average more 
conserved during evolution than the genes with lower expression levels. This 
correlation was conceptualized in the misfolding-driven protein evolution 
hypothesis according to which misfolding is the principal cost incurred by 
protein expression. We sought to determine whether long intergenic ncRNAs 
(lincRNAs) follow the same evolutionary trend and indeed detected a moderate but 
statistically significant negative correlation between the evolutionary rate and 
expression level of human and mouse lincRNA genes. The magnitude of the 
correlation for the lincRNAs is similar to that for equal-sized sets of 
protein-coding genes with similar levels of sequence conservation. Additionally, 
the expression level of the lincRNAs is significantly and positively correlated 
with the predicted extent of lincRNA molecule folding (base-pairing), however, 
the contributions of evolutionary rates and folding to the expression level are 
independent. Thus, the anticorrelation between evolutionary rate and expression 
level appears to be a general feature of gene evolution that might be caused by 
similar deleterious effects of protein and RNA misfolding and/or other factors, 
for example, the number of interacting partners of the gene product.