Zmat2 in mammals: conservation and diversification among genes and Pseudogenes

Abstract

Background Recent advances in genetics and genomics present unique opportunities for enhancing our understanding of mammalian biology and evolution through detailed multi-species comparative analysis of gene organization and expression. Yet, of the more than 20,000 protein coding genes found in mammalian genomes, fewer than 10% have been examined in any detail. Here we elucidate the power of data available in publicly-accessible genomic and genetic resources by querying them to evaluate Zmat2, a minimally studied gene whose human ortholog has been implicated in spliceosome function and in keratinocyte differentiation. Results We find extensive conservation in coding regions and overall structure of Zmat2 in 18 mammals representing 13 orders and spanning ~ 165 million years of evolutionary development, and in their encoded proteins. We identify a tandem duplication in the Zmat2 gene and locus in opossum, but not in other monotremes, marsupials, or other mammals, indicating that this event occurred subsequent to the divergence of these species from one another. We also define a collection of Zmat2 pseudogenes in half of the mammals studied, and suggest based on phylogenetic analysis that they each arose independently in the recent evolutionary past. Conclusions Mammalian Zmat2 genes and ZMAT2 proteins illustrate conservation of structure and sequence, along with the development and diversification of pseudogenes in a large fraction of species. Collectively, these observations also illustrate how the focused identification and interpretation of data found in public genomic and gene expression resources can be leveraged to reveal new insights of potentially high biological significance.

The Zmat2 gene in non-mammalian vertebrates: Organizational simplicity within a divergent locus in fish

“…Our investigations found that in addition to the strong conservation of the protein and of protein-coding exons, a remarkable feature about mammalian Zmat2 is the presence of pseudogenes in half of the species that we have examined to date [11]. Moreover, based on phylogenetic analysis, it appears that these pseudogenes are relatively recent additions to their respective genomes, and have each arisen independently of one another during speciation [11].…”

“…Human ZMAT2 and other mammalian Zmat2 genes had been incompletely characterized in the Ensembl and UCSC genomic repositories, but as shown in our recent studies, they comprise a highly conserved series of orthologous genes and proteins [11]. In 17 of 18 mammalian genomes analyzed, Zmat2 was found to be a single copy gene, with the single exception being a tandem duplication identified in the opossum genome.…”

“…In 17 of 18 mammalian genomes analyzed, Zmat2 was found to be a single copy gene, with the single exception being a tandem duplication identified in the opossum genome. As Zmat2 was present in a single copy in other monotremes and marsupials, the duplication event most likely occurred after the divergence of these species from each other [11]. We also determined that the genomes of nine of the mammals studied contained one or more Zmat2 pseudogenes, and that based on phylogenetic analysis, the insertion of each of these pseudogenes into each genome occurred after the divergence of each individual mammal from its nearest ancestor [11].…”

“…To test this idea, we recently evaluated the Zmat2 gene in 18 mammalian species, [11]. Mammalian ZMAT2 had been essentially unstudied until a single publication in 2018 focused on its actions in human keratinocyte differentiation [12].…”

ZMAT2 in Humans and Other Primates: A Highly Conserved and Understudied Gene

“…29 Other recently published studies from our group have demonstrated that Zmat2 pseudogenes are present in at least 9 other mammalian species. 34 As the DNA sequence of each of these pseudogenes was more similar to the paralog from the homologous mammalian species than to other Zmat2 pseudogenes, it seems likely that each Zmat2 pseudogene arose independently subsequent to the divergence of each mammal from its closest ancestors. 34 population allelic variants: 0% 0.005% 0.009% The overall population prevalence of variant alleles for each segment of the protein is listed above the map, and the number of missense mutations in various cancers is found below.…”