The three dimensional structures of CEACAM N domains were modeled using the Geno3D-release 2 software based on the published crystal structure of the murine CEACAM1 N-A2 fragment [37, 52] . Leader and transmembrane domains were identified with the aid of programs SignalP and TMHMM, respectively. The NetPhos 2.0 server was used to produce neural network predictions for serine, threonine and tyrosine phosphorylation sites in the cytoplasmic domains of canine CEACAMs [53] . Comparison of the number of nonsynonymous substitutions per nonsynonymous site (Ka) with the number of synonymous substitutions per synonymous site (Ks) was performed with the Ka/Ks Calculation Tool [54] . The substitution rate ratio Ka/Ks measures the molecular selective pressure. If Ka/Ks = 1, the amino acid changes are neutral and will be fixed at the same rate as silent mutations. If Ka/Ks < 1, the amino acid changes are deleterious and purifying selection will reduce the fixation rate. If Ka/ Ks > 1, the amino acid changes are evolutionarily advantageous and positive selection will increase the fixation rate. Nucleolus: the fascinating nuclear body Nucleoli are the prominent contrasted structures of the cell nucleus. In the nucleolus, ribosomal RNAs are synthesized, processed and assembled with ribosomal proteins. RNA polymerase I synthesizes the ribosomal RNAs and this activity is cell cycle regulated. The nucleolus reveals the functional organization of the nucleus in which the compartmentation of the different steps of ribosome biogenesis is observed whereas the nucleolar machineries are in permanent exchange with the nucleoplasm and other nuclear bodies. After mitosis, nucleolar assembly is a time and space regulated process controlled by the cell cycle. In addition, by generating a large volume in the nucleus with apparently no RNA polymerase II activity, the nucleolus creates a domain of retention/sequestration of molecules normally active outside the nucleolus. Viruses interact with the nucleolus and recruit nucleolar proteins to facilitate virus replication. The nucleolus is also a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm by nucleolus disruption. The nucleolus plays several crucial functions in the nucleus: in addition to its function as ribosome factory of the cells it is a multifunctional nuclear domain, and nucleolar activity is linked with several pathologies. Perspectives on the evolution of this research area are proposed. Brief history of the nucleolus An ovoid body visible in the nucleus was probably the Wrst observation of the nucleolus more than two centuries ago by F. Fontana. Since that time, the nucleolus has been the object of intense investigation and interestingly our vision of the nucleolus has evolved with technical progress. During the nineteenth century, using light microscopy, numerous cytologists described the variability of nucleolar morphology with great precision (Montgomery 1898) . In 1934, McClintock proposed that the "nucleolus is organized in the telophase through the activity of ... the nucleolar-organizing body" (McClintock 1934) . Since the nucleolar-organizing body corresponds to a speciWc region of chromosome 6 in Zea mays, this was the Wrst time the nucleolus was related to gene activity. In the 1950's the presence of RNAs in the nucleolus was demonstrated, and in the 1960's in situ hybridization techniques made it possible to identify ribosomal genes (rDNAs) in the nucleolar organizer region (NOR) (Caspersson 1950; Perry 1962; Ritossa and Spiegelman 1965) . During the same period, mass isolation of nucleoli became possible leading to the biochemical characterization of nucleolar components. Based on these results it was proposed that ribosome biogenesis occurs in nucleoli. Given that the nucleolus became a subject of great interest, the "International symposium on the nucleolus-its structure and function" was organized in Montevideo in 1965 and the contributions published in Natl Cancer Inst Monogr no 23 (USA) in 1966. Since 1969, at the initiative of W. Bernhard and H. Busch, "Nucleolar Workshops" on nucleolar organization, the biochemistry of nucleolar proteins, rRNA processing as well as variability in cancer cells were regularly organized. Several books on nucleoli were published; among them, the famous "The nucleolus and ribosome biogenesis" is still a very useful source of information (Hadjiolov 1985) . Between 1980 and 2000, the functional organization of the nucleolus was deciphered in large part due to the improvement of labeling by the electron microscopy (EM).