The lipocalins constitute a family of proteins that have been found in euba
cteria and a variety of eukaryotic cells, where they play diverse physiolog
ical roles. It is the primary goal of this review to examine the patterns o
f change followed by lipocalins through their complex history, in order to
stimulate scientists in the field to experimentally contrast our phylogeny-
derived hypotheses. We reexamine our previous work on lipocalin phylogeny a
nd update the phylogenetic analysis of the family. Lipocalins separate into
14 monophyletic clades, some of which are grouped in well supported superc
lades. The lipocalin tree was rooted with the bacterial lipocalin genes und
er the assumption that they have evolved from a single common ancestor with
the metazoan lipocalins, and not by horizontal transfer. The topology of t
he rooted tree and the species distribution of lipocalins suggest that the
newly arising lipocalins show a higher rate of amino acid sequence divergen
ce, a higher rate of gene duplication, and their internal pocket has evolve
d towards binding smaller hydrophobic ligands with more efficiency. (C) 200
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