The genome is not as static as a well-tended garden. It has its wild side. New genes emerge continuously. Some even sprout like weeds from genomic regions once devoid of functional DNA. These seemingly unlikely outgrowths needn’t be copies or modified versions of existing genes. Instead, they can be entirely new, pushing evolutionary processes in new directions, especially if they become intensively cultivated—transcriptionally speaking.
Although some newly expressed genes acquire coding or noncoding functions and are preserved by natural selection, the underlying mechanisms of de novo gene emergence remain obscure. To help bring these mechanisms to light, a team of researchers led by Jorge Ruiz-Orera and Mar Albà from Hospital del Mar Medical Research Institute in Barcelona (IMIM-ICREA) has examined RNA-Seq data from eight mammalian species, including human, chimpanzee, macaque, and mouse.
The team reports that it succeeded in defining sets of putative newly born genes in human and chimpanzee genes and is investigating what drives the expression of these genes. The team asserts that its work represents the largest-scale project of its kind to address the origin of de novo genes.
The team published its results December 31 in the journal PLOS Genetics, in an article entitled, “Origins of De Novo Genes in Human and Chimpanzee.” The article describes how the team started by identifying thousands of genes that were specific to human or chimpanzee. These are genes that are unique to that particular species, that is, lacking homologues in any other species.
Next, the team searched the macaque genome and discovered that this species had significantly fewer element motifs in the corresponding genomic sequences. These motifs are recognized by proteins that activate gene expression, a necessary step in the formation of a new gene.
“[We identified] over five thousand new multiexonic transcriptional events in human and/or chimpanzee that are not observed in the rest of species,” wrote the article’s authors. “Using comparative genomics, we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS.”
The researchers found that these transcripts generally showed little evidence of purifying selection, suggesting that many of them are not functional. However, the researchers also found signatures of selection in a subset of de novo genes that have evidence of protein translation. “Taken together,” the authors noted, “the data support a model in which frequently occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins.”
The formation of genes de novo from previously nonactive parts of the genome was, until recently, considered highly improbable. This study has shown that the mutations that occur normally in our genetic material may be sufficient to explain how this happens. Once expressed, the genes can act as a substrate for the evolution of new molecular functions. This study identified several candidate human proteins that bear no resemblance to any other known protein. What they do is an enigma still to be resolved.