Independent evolution for sex determination and differentiation in the DMRT family in animals

Abstract

Some DMRT family genes including arthropod dsx, nematode mab-3, and vertebrate dmrt1 are involved in sex determination and/or differentiation in bilaterian animals. Although there have been some reports about evolutionary analyses of the family by using its phylogenetic trees, it is still undecided as to whether these three sex determination-related genes share orthologous relationships or not. To clarify this question, we analyzed evolutional relationships among the family members in various bilaterians by using not only phylogenetic tree analysis, but also synteny analysis. We found that only four genes, dmrt2a/2b, dmrt3, dmrt4/5 and dmrt93B were commonly present in invertebrate bilateria. The syntenies of dmrt2a/2b-dmrt3 and dmrt4/5-dmrt93B are conserved before and after two rounds of whole genome duplication in the ancestral vertebrate. Importantly, this indicates that dmrt1 must have appeared in the common vertebrate ancestor. In addition, dmrt1, dsx, or mab-3 formed each different cluster at a distance in our phylogenetic tree. From these findings, we concluded that the three sex determination-related genes, dmrt1, dsx, and mab-3 have no orthologous relationships, and suggested independent evolution for sex determination and differentiation in the DMRT gene family. Our results may supply clues about why sex-determining systems have diverged during animal evolution.

Comparative transcriptome analysis of three gonadal development stages reveals potential genes involved in gametogenesis of the fluted giant clam (Tridacna squamosa)

“…Doublesex-and mab-3-related transcription factor (DMRT) is a sex determining gene that is essential for the maintenance of male-specified germ cells and testis differentiation [53,54]. At present, eight members of the family (DMRT1-8) have been reported in vertebrates [55]. In mollusks, orthologs of DMRT have been characterized from the oysters C. gigas [56], P. martensii [14] and Pinctada fucata [57].…”

Comparative Genomics Studies on the dmrt Gene Family in Fish

“…Johnsen and Andersen (2012) performed chromosomal synteny analysis on dmrt2a and dmrt2b, and proposed that these genes originated from the second round (2R) of whole genome duplication of the ancestral dmrt2 (Johnsen and Andersen, 2012). In turn, Mawaribuchi et al (2019) performed phylogenetic cluster analysis of lower bilaterian and higher animal dmrt genes, based on which they speculated that the dmrt3 gene emerged by genome duplication (1R), and dmrt1 and dmrt6 emerged after the 2R genome duplication; they also proposed an evolutionary history for the dmrt family genes in bilateria (Mawaribuchi et al, 2019). Therefore, according to our data coupled with these relevant literatures, we hypothesized evolutionary history of the dmrt genes in fish (Figure 6).…”

Ubiquitin-dependent regulation of a conserved DMRT protein controls sexually dimorphic synaptic connectivity and behavior

“…However, the DMRT family has radiated in distinct animal phyla, generating clade-specific family members. For example, the well-studied doublesex gene is an arthropod-specific DMRT gene ( Mawaribuchi et al, 2019 ). We have described here the expression and function of a DMRT gene, C. elegans dmd-4, that in contrast to doublesex is conserved throughout the animal kingdom and find that this gene plays a critical role in sculpting sexually dimorphic synaptic connectivity patterns.…”

“…We reveal here a different mechanism that involves an evolutionarily ancient domain, the DMA domain. Phylogenetic analysis of the DMRT gene family suggests that the presence of a DMA domain was characteristic of the three ancestral gene clusters, and arose before the evolution of eumetazoans, but this domain has not been maintained in all extant DMRT clusters ( Mawaribuchi et al, 2019 ; Wexler et al, 2014 ). In C. elegans , dmd-4 represents the only gene that encodes a DMA domain, which we identify here as required for protein stability and able to bind monoubiquitin, consistent with its sequence similarity to the CUE domains of the UBA family.…”

“…DMRT-encoding genes evolved from three ancestral clusters of genes that were present in the ancestor of bilateria and radiated independently in multiple distinct lineages unique to each phylum ( Mawaribuchi et al, 2019 ; Volff et al, 2003 ; Wexler et al, 2014 ). Those DMRT proteins most extensively characterized in controlling sex-specific differentiation in the brain – mab-3 , mab-23 , and dmd-3 in C. elegans and doublesex in Drosophila ( Lints and Emmons, 2002 ; Mason et al, 2008 ; Rideout et al, 2010 ; Siehr et al, 2011 ; Taylor et al, 1994 ; Verhulst and van de Zande, 2015 ; Yi et al, 2000 ) – are examples of such radiated DMRTs.…”