Open questions in the study of de novo genes: what, how and why

• Published in: Nature reviews. Genetics Vol. 17; no. 9; pp. 567 - 578
• Main Authors: McLysaght, Aoife, Hurst, Laurence D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2016; Nature Publishing Group
• Subjects: 631/181; 631/181/735; 631/208/191; 631/208/212; Agriculture; Amino acid sequencing; Animal Genetics and Genomics; Bias; Biomedicine; Cancer Research; Evolution; Evolution, Molecular; Gene Function; Genes; Genetic research; Genomes; Genomics - methods; Genotypes; Human Genetics; Humans; Identification and classification; Methods; Open Reading Frames - genetics; opinion-2; Phylogeny; Proteins; Proteins - genetics; Proteins - metabolism
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg.2016.78

In this Opinion article, the authors discuss important questions relating to the study of de novo genes. They discuss the challenges of identifying de novo genes, understanding how they originate and why they spread, and propose that antagonistic evolution may have a key role in their evolution. The study of de novo protein-coding genes is maturing from the ad hoc reporting of individual cases to the systematic analysis of extensive genomic data from several species. We identify three key challenges for this emerging field: understanding how best to identify de novo genes, how they arise and why they spread. We highlight the intellectual challenges of understanding how a de novo gene becomes integrated into pre-existing functions and becomes essential. We suggest that, as with protein sequence evolution, antagonistic co-evolution may be key to de novo gene evolution, particularly for new essential genes and new cancer-associated genes.