Sequence-Function Relationships Within the Expanding Family of Prolactin, Growth Hormone, Placental Lactogen, and Related Proteins in Mammals*

Abstract

I. Introduction PRL PL, and GH are homologous proteins that are thought to have arisen from a common ancestral gene by two successive tandem duplications (Refs. 1–5; for review, see Ref. 6). PRL and GH are mainly secreted by the anterior pituitary of all vertebrates. The divergence of the PRL and GH lineage from the common ancestral gene has been located some 400 million years ago, which is in good agreement with the presence of distinct PRL and GH in fish (2, 3, 6, 7). PL is uniquely observed in mammals and is secreted in the placenta by syncytiotrophoblastic cells (for reviews, see Refs. 8–10). Initially, PLs were proposed to have evolved from the common PRL/GH precursor gene (1). Further cloning and analysis of PRL, GH, and PL genes from different species (chromosome carrier, gene size, splicing sites, sequence identity; see Refs. 6, 7, 11, and 12) have led to a reconsideration of this hypothesis, and it is now assumed that primate PLs evolved from the GH lineage while nonprimate PLs arose from the PRL...