De novo emergence, existence, and demise of a protein-coding gene in murids

• Published in: BMC biology Vol. 20; no. 1; pp. 272 - 14
• Main Authors: Petrzilek, Jan, Pasulka, Josef, Malik, Radek, Horvat, Filip, Kataruka, Shubhangini, Fulka, Helena, Svoboda, Petr
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.12.2022; BioMed Central; BMC
• Subjects: Amino acid sequence; Animals; CAG; Complexity; De novo; Evolution; Evolutionary genetics; Fertility; Gametocytes; Gene; Gene expression; Gene sequencing; Genes; Genetic aspects; Genetic research; Genomes; Hamsters; Identification and classification; Laboratory animals; Long terminal repeat; LTR; Molecular evolution; Muridae; Muroidea; Mutation; Natural history; Non-coding RNA; Polyglutamine; Protein biosynthesis; Proteins; Retrotransposon; RNA, Long Noncoding - genetics; Rodents; Transcriptomes; Trinucleotide repeats; Czech Republic; Retrotransposon; Gene; CAG; Evolution; LTR; De novo; Oocyte; Polyserine; D6Ertd527e
• ISSN: 1741-7007; 1741-7007
• DOI: 10.1186/s12915-022-01470-5

Genes, principal units of genetic information, vary in complexity and evolutionary history. Less-complex genes (e.g., long non-coding RNA (lncRNA) expressing genes) readily emerge de novo from non-genic sequences and have high evolutionary turnover. Genesis of a gene may be facilitated by adoption of functional genic sequences from retrotransposon insertions. However, protein-coding sequences in extant genomes rarely lack any connection to an ancestral protein-coding sequence. We describe remarkable evolution of the murine gene D6Ertd527e and its orthologs in the rodent Muroidea superfamily. The D6Ertd527e emerged in a common ancestor of mice and hamsters most likely as a lncRNA-expressing gene. A major contributing factor was a long terminal repeat (LTR) retrotransposon insertion carrying an oocyte-specific promoter and a 5' terminal exon of the gene. The gene survived as an oocyte-specific lncRNA in several extant rodents while in some others the gene or its expression were lost. In the ancestral lineage of Mus musculus, the gene acquired protein-coding capacity where the bulk of the coding sequence formed through CAG (AGC) trinucleotide repeat expansion and duplications. These events generated a cytoplasmic serine-rich maternal protein. Knock-out of D6Ertd527e in mice has a small but detectable effect on fertility and the maternal transcriptome. While this evolving gene is not showing a clear function in laboratory mice, its documented evolutionary history in Muroidea during the last ~ 40 million years provides a textbook example of how a several common mutation events can support de novo gene formation, evolution of protein-coding capacity, as well as gene's demise.