Abstract
The nuclear receptor gene family includes 18 members that are broadly conserved among multiple disparate animal phyla, indicating that they trace their evolutionary origins to the time at which animal life arose. Typical nuclear receptors contain two major domains: a DNA-binding domain and a C-terminal domain that may bind a lipophilic hormone. Many of these nuclear receptors play varied roles in animal development, including coordination of life cycle events and cellular differentiation. The well-studied genetic model systems of Drosophila, C. elegans, and mouse permit an evaluation of the extent to which nuclear receptor function in development is conserved or exapted (repurposed) over animal evolution. While there are some specific examples of conserved functions and pathways, there are many clear examples of exaptation. Overall, the evolutionary theme of exaptation appears to be favored over strict functional conservation. Despite strong conservation of DNA-binding domain sequences and activity, the nuclear receptors prove to be highly-flexible regulators of animal development.
Highlights
The nuclear receptor gene family includes 18 members that are broadly conserved among multiple disparate animal phyla, indicating that they trace their evolutionary origins to the time at which animal life arose
Among the earliest nuclear receptors (NRs) to be defined by mutation are androgen receptor in mice in 1970 [1], unc-55/COUP-TF in C. elegans in 1973 [2], knirps in Drosophila in 1980 [3], and daf-12 in C. elegans in 1981 [4]. While their molecular identity and characterization as NRs largely required the development of positional cloning strategies of the 1980’s, there is a long record of genetic analysis of NRs in model systems
The typical nuclear receptor includes two major domains: a DNA-binding domain (DBD) that allows sequence-specific binding to DNA, and a ligand-binding domain (LBD) that binds a lipophilic hormone in some cases
Summary
The nuclear receptor gene family includes 18 members that are broadly conserved among multiple disparate animal phyla, indicating that they trace their evolutionary origins to the time at which animal life arose. The C. elegans HR3 ortholog, nhr-23, plays an apparently similar role in coordinating molting and developmental transitions. Analysis of expression patterns and a chromosomal deletion suggested that HNF4 might play a role in fly gastrulation and gut development as in vertebrates [104].
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