Abstract
The majority of human genes are conserved among mammals, but some gene families have undergone extensive expansion in particular lineages. Here, we present an evolutionary analysis of one such gene family, the poly–zinc-finger (poly-ZF) genes. The human genome encodes approximately 700 members of the poly-ZF family of putative transcriptional repressors, many of which have associated KRAB, SCAN, or BTB domains. Analysis of the gene family across the tree of life indicates that the gene family arose from a small ancestral group of eukaryotic zinc-finger transcription factors through many repeated gene duplications accompanied by functional divergence. The ancestral gene family has probably expanded independently in several lineages, including mammals and some fishes. Investigation of adaptive evolution among recent paralogs using dN/dS analysis indicates that a major component of the selective pressure acting on these genes has been positive selection to change their DNA-binding specificity. These results suggest that the poly-ZF genes are a major source of new transcriptional repression activity in humans and other primates.
Highlights
Coordinated evolution of complex characters can occur by altering regulatory genes that control large suites of effector genes [1]
Most human ZF proteins have an architecture consisting of an Nterminal domain that interacts with other proteins and a Cterminal region that consists of C2H2 (Kruppel-type) zinc finger domains that bind DNA
There is no single good criterion for assigning a protein as a member of the poly-ZF gene family, so we ascertained a set that is probably larger than the true poly-ZF gene family but should contain all true poly-ZF proteins
Summary
Coordinated evolution of complex characters can occur by altering regulatory genes that control large suites of effector genes [1]. A small number of changes in these regulatory genes can result in conspicuous and harmonious changes in developmental pattern, reproduction, or physiology, because they co-opt entire functional networks of other genes. These evolving regulatory genes usually encode transcription factors or signaling proteins, and their evolution appears often to involve gene duplication and diversification [1]. Half of all annotated transcription factors in the human genome belong to the C2H2 zinc finger (ZF) superfamily [2,3,4]. The number of zinc finger repeats in poly-ZF proteins varies in humans from 4 to more than 30, with a mean of about 8.5. Most of the ZF repeats in these proteins are present in tandem and they are remarkably homogeneous in their spacing and core structure: most are 21 amino acids long with the pattern CX2-C-X12-H-X3-H, and they are separated from each other by a 7 amino acid linker of conserved sequence
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