The present study examines 783 human-mouse orthologous gene pairs for their pattern of sequence evolution, contrasting mammalia, eukaryota, coelomata, and bilateria specific human intronless genes. Such comparisons may be of use in understanding the general evolution of human genome. Evolutionary rate analyses indicate that mammalia specific human intronless genes are evolving faster as compared to other intronless genes specific to eukaryotic lineage, indicating towards their rapid evolution. The observations indicates that the genes conserved in eukaryota, coelomata, and bilateria, that is, proteins that arose earlier in evolution as compared to mammalia specific genes evolve slowly and are subjected to negative selection. The cause underlying rate variations was also explored. Although mutational bias might slightly fasten the nonsynonymous rates in mammalia specific genes, it is unlikely to be major cause of rate difference between the various categories. Furthermore, rate of divergence of mammalia specific intronless genes has been related to functional classification using the protein family annotation. Protein function was found in some cases to have larger impact on the rate of evolution of genes. Also, the codon usage pattern of mammalia specific intronless genes do not seem to differ much from those of other intronless genes conserved solely in eukaryotic lineage.