1 979) Nudcic Acids Rrs. 6, 2435 -24521 of chicken ovotransferrin (conalbumin) mRNA has been determined. Taking into account the previously reported 5'-end sequence [Cochet, M., Gannon, F., Hen, R., Maroteaux, L., Perrin, F., and Chambon, P. (1979) Nature (Lond.) 282, 567 -5741 we present the complete nucleotide sequence of the ovotransferrin mRNA from which the amino acid sequence of the protein is inferred. A computer and statistical analysis of the nucelotide sequence reveals a pattern of internal homology which confirms that the present-day chicken ovotransferrin gene (and by extrapolation the transferrin genes of other species) has evolved by duplication and gives some support to the quadruplication hypothesis of transferrin evolution.The avian transferrin gene is interesing in several respects. It is expressed both in the liver and in the oviduct, where its protein products are known as serum transferrin and ovotransferrin (or conalbumin) respectively. The liver and the oviduct proteins differ only in the nature of their attached glycan chain [3, 41. However, the modulation of the expression of the transferrin gene by steroid hormones and iron levels is very different in the two organs [2, 5, 61. Determination of partial amino-acid sequences of the N-terminal and C-terminal ends of the protein, X-ray crystallography studies and partial proteolysis experiments on human, chicken and rabbit transferrins have led to the hypothesis that the present-day transferrin gene has evolved by duplication from an ancestral gene [7-101. Moreover, it has been proposed that this ancestral gene could be itself the product of a more ancient duplication [8] and, therefore, that the present-day transferrins could be the product of a quadruplication event.We have previously reported that the chicken transferrin gene is split in 17 exons [2]. The complete elucidation of the structure of the transferrin gene a t the sequence level should reveal some of the mechanisms involved in the generation of split genes by duplication and possibly quadruplication of ancestral genes. Such a study should disclose whether the ancestral gene(s) was (were) already split and how the original exon-intron pattern has evolved since the duplication events. The presence of two homologous iron-binding domains in transferrins [7,9, 101 will also provide an opportunity to see if the proposal that exons could correspond to functional domains applies to this gene [ll].To address these questions and to form a basis for further studies of the ovotransferrin gene structure, we have determined the nucleotide sequences of an almost full-length ovotransferrin double-stranded cDNA clone [I]. This sequence, together with the previously reported sequence of the 5' Abbreviation. dscDNA, double-stranded complementary D N A .