De novo origin of human protein-coding genes

Abstract

The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA-seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes.

Figure 1. Pipeline for the identification of de novo originated protein-coding genes in the human genome.

BLASTP searches of human protein sequences against proteins of other primates identified 548 human genes without protein orthologs. After excluding these genes having no start or stop codons, 352 human coding sequences were used in BLAT searches to find orthologous genes in chimpanzee and orangutan and these sequences were examined to confirm the presence of disrupting mutations. 66 genes with disrupted open reading frames in chimpanzee and orangutan were examined to identify those with human-specific mutations that generate intact open reading frames, resulting 46 candidates. These genes were used as queries of mRNA and proteomic databases to confirm transcription and translation. The pipeline yielded 27 de novo originated protein-coding genes.

Figure 2. Levels of expression of de novo genes in 11 tissues.

(A) Mean normalized expression levels of de novo originated genes in 11 tissues are defined by the mean level of expression as the numbers of unique reads mapping to coding regions divided by the total length of all the coding regions, divided by the total number of valid reads in the samples (×10⁻⁸). The vertical axis represents value of mean the normalized expression levels and abscissa axis represents the 11 tissues. (B) The proportion of the de novo originated genes that have expressed reads in the 11 tissues. The vertical axis represents the values of proportion, and abscissa axis represents the 11 tissues. (C) The proportion of the de novo originated genes having their highest normalized expression levels in each of the 11 tissues. The vertical axis represents the values of proportion, and abscissa axis represents the 11 tissues.

Figure 3. Rate of evolution of de novo originated genes.

Rate of de novo originated genes on the human lineage and orthologous sequences on the chimpanzee lineage are compared to the average genome wide genes. Lineage specific substitution rates (+standard deviation) of the de novo genes and genome-wide genes are presented.