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Although, as their names imply, estrogen receptors [ERs] and estrogen-related receptors [ERRs] are related transcription factors, their evolutionary relationships to each other are not fully understood. To elucidate the origins and evolution of ERs and ERRs, we searched for their orthologs in the recently sequenced genome of  Trichoplax , the simplest known animal, and in the genomes of three lophotrochozoans:  Capitella , an annelid worm,  Helobdella robusta , a leech, and  Lottia gigantea , a snail. BLAST searches found an ERR in  Trichoplax , but no ER. BLAST searches also found ERRs in all three lophotrochozoans and invertebrate-like ERs in  Capitella  and  Lottia , but not in  Helobdella . Unexpectedly we find that the  Capitella  ER sequence is closest to ER[beta], unlike the other invertebrate ER sequences, which are closest to ER[alpha]. Our database searches and phylogenetic analysis indicate that invertebrate ERs evolved in a lophotrochozoan and steroid-binding ERs evolved in a deuterostome.

Trichoplax, the simplest known animal, contains an estrogen-related receptor but no estrogen receptor: Implications for estrogen receptor evolution