New gene evolution: little did we know

Abstract

Genes are perpetually added to and deleted from genomes during evolution. Thus, it is important to understand how new genes are formed and how they evolve to be critical components of the genetic systems that determine the biological diversity of life. Two decades of effort have shed light on the process of new gene origination and have contributed to an emerging comprehensive picture of how new genes are added to genomes, ranging from the mechanisms that generate new gene structures to the presence of new genes in different organisms to the rates and patterns of new gene origination and the roles of new genes in phenotypic evolution. We review each of these aspects of new gene evolution, summarizing the main evidence for the origination and importance of new genes in evolution. We highlight findings showing that new genes rapidly change existing genetic systems that govern various molecular, cellular, and phenotypic functions.

Figure 1

New genes are defined using syntenic and sequence comparisons between the genomes of a group of related species. A) The general procedure to identify new genes. The relationship of species S1–S4 is shown by the blue tree. The relationships between the genes G1 (yellow), G2 (red), and G3 (green) are shown within the species tree. Aligning the genomes of species S1–S4 shows that the new gene G2 is present in S1-S3 but absent in S4, indicating that G2 arose in the common ancestor of S1–S3. G2 was thus generated in the genome between old genes G1 and G3 in the common ancestor of S1, S2, and S3 (red star). B) An example of using syntenic alignments to identify new genes. Sdic exists only in Drosophila melanogaster (99). In this case, Sdic originated as a chimeric gene through recombination of duplicates of the two flanking genes, a 5’ piece of Cdic encoding a cytoplasmic dynein intermediate chain and a 3’ piece of AnnX (see text for further details).

Figure 2

Representative new genes exhibiting various new gene origination mechanisms. A) Jingwei, a new gene found only in D. teissieri and D. yakuba, was generated by a combination of retroposition, DNA-based duplication and gene recombination which formed a chimeric gene consisting of Adh-derived enzymatic domain and a hydrophobic domain from Ymp (74,133). B) PIPSL in humans is a consequence of gene fusion between two adjacent ancestral genes by read-through transcription and subsequent co-retroposition (152). C) Gene fission split the ancestral gene monkeyking into two distinct genes in D. mauritiana, revealing an intermediate process of gene fission aided by gene duplication and complementary degeneration (134). D) The gene ENSMUSG00000078384 in mouse revealed the evolutionary process of de novo gene origination (93). E) Two new genes in humans, DAF and mNSCI, were generated by domesticating transposable elements, Alu and short interspersed elements (B1-B4) (89, 104). DAF and Alu elements is a neat case where alternative splicing generated a new isoform in the mammalian genome. F) Horizontal gene transfer (HGT) is prevalent in bacteria with mechanisms including homologous recombination (101). Antibiotic resistance genes can be acquired by host genomes containing the intl gene, which encodes integrase, a recombination site (att), and a promoter to express the captured gene, as depicted by the process on the left. See the text for more details.

Figure 3

The phylogenetic distribution of new gene origination events in Drosophila and vertebrates. These genes are only those that were generated by DNA-based duplication, retroposition and de novo origination (162, 163). The number of new genes that originated in each time period is shown above the branch. For example, branch 1 in A) shows that 220 genes originated between 36 and 41 MYA in Drosophila. In B) red numbers are new genes that originated in the hominoid branches or specifically in humans.

Figure 4

Retrogene traffic in Drosophila (A; 10, 138) and humans (B; 42). Each arrow indicates the movement of retrogenes from the parental gene chromosomal location to the retrogene’s location. The size of arrow indicates the intensity of gene movement between chromosomes, and the percentages show quantitatively the excess of movement over the null expectation (random origination and insertion). The functions of the retrogenes are indicated.

Figure 5

Positive Darwinian selection acting on new genes in Drosophila. A) Positive selection for the fixation of new retrogenes in Drosophila (120) and humans (119). The numerator and denominator show the numbers of retrogenes that originate on the autosomes and the X, respectively. Tests based on the M-K framework indicate an excess of fixed X→A retrogenes in both species, and strong positive selection for X→A retrogene movement. B) The jingwei gene (81). The ratios over the branches are the numbers of nonsynonymous changes over the numbers of synonymous changes, while the ratios in the triangles are the ratios of divergence between the species to polymorphisms. M–K tests and Ka/Ks ratios indicate strong positive selection acted on jgw shortly after it originated. C) Selection acted on all Adh-derived chimeric genes in Drosophila (63), as indicated by elevated Ka/Ks ratios.

Figure 6

The essential effects of new genes on development. A) Development was terminated at the final stage of development when three different genes were knocked down using RNA interference (RNAi). B) YLL1 originated in the common ancestor of the D. melanogaster subgroup species 6~10 MYA, yet showed lethal effects in the pupal stage when silenced by RNAi, mutated by EMS or disrupted by P-element (29).

Figure 7

New genes integrated into and reshaped gene networks. A) Yeast new genes that originated through duplication-based (blue) and non-duplication-based (red) mechanisms since the recent whole genome duplication (<100 MYA) were integrated into the physical interaction network (17). The orange box highlights a module composed of two new genes involved in the pathway to form and process actin. DID4 (green box) interacts with 13 new genes within a few steps. B) New genes form hubs in protein-protein interaction networks (29). C) The D. melanogaster-D. simulans-specific gene Zeus quickly accumulated more than 100 amino acid substitutions in its nucleotide binding domains under positive selection. Consequently, it evolved into a new DNA binding motif that evolved hundreds of new gene links to rewire the gene networks that control reproduction (27).