study was focused on a particular class of genes predicted to be non-orthologous between cow and human genomes. These genes are normally considered the result of divergent evolution and are reported by the automated pipelines and following the manual annotations of the bovine and dog genome in the international sequencing projects [ 31 , 36 ]. Evidence found within this work suggest that a high number of non-orthologous genes between cow and human could be considered a side effect of an incomplete genome assembly and annotation process. The approach described here allowed the differences and similarities for this class of genes to be highlighted and also possible new features for the human genome to be identified. The comparison between species, using similarity and classification methods, is crucial for the analysis of genome sequences and gene sets, especially when the annotation process relies on the quantity and quality of available data on transcript sequences for a particular species. In this context, this kind of comparative approach could be used to extend the current genome annotation protocols. The presence of non-orthologous genes in other species should be considered as a central resource to derive important information for the definition of gene models and structures, in particular for the newly assembled genomes, where the lack of a complete set of genes and poor transcript sequences information may restrict the commonly applied annotation procedures. Methods Datasets The cow genome assembly version 4.0 and the human genome assembly version 36 were downloaded from Ensembl release