Source gene composition and gene conversion of the AluYh and AluYi lineages of retrotransposons

Abstract

Background: Alu elements are a family of SINE retrotransposons in primates. They are classified into subfamilies according to specific diagnostic mutations from the general Alu consensus. It is now believed that there may be several retrotranspositionally-competent source genes within an Alu subfamily. In this study, subfamilies falling on the AluYi and AluYh lineages, and the AluYg6 subfamily, are assessed for the presence of secondary source genes, and the influence of gene conversion on the AluYh and AluYi lineages is also described.

Results: The AluYh7 and AluYi6 subfamilies appear to contain multiple source genes. The novel subfamilies AluYh3a1 and AluYh3a3 are described, for which there is no convincing evidence to suggest the presence of secondary sources. The mutational substructure of AluYh3a3 can be explained completely by inference of single master gene. A complete backwards gene conversion event appears to have inactivated the AluYh3a3 master gene in humans. Polymorphism data suggest a larger number of secondary source elements may be active in the AluYg6 family than previously thought.

Conclusion: It is clear that there is considerable variation in the number of source genes present in each of the young Alu subfamilies. This can range from a single master source gene, as for AluYh3a3, to as many as 14 source elements in AluYi6.

Figure 1

Alignment of the AluYh7, AluYh3a1 and AluYh3a3 consensus sequences with AluY. Diagnostic mutations from AluY can be seen for each subfamily. Mutations from AluY shared by all three subfamilies on the AluYh lineage are shown in black boxes. The further mutations accumulated by the AluYh7 subfamily are shown in blue boxes. The mutation possessed by AluYh3a1 and AluYh3a3 is shown in a red box, and the further two mutations in AluYh3a3 are shown in green boxes.

Figure 2

Relationships between the subfamilies on the AluYh lineage. Diagnostic mutations for each new subfamily are shown on the arrow leading to that subfamily. The copy numbers of each of these subfamilies are listed in table 1.

Figure 3

Alignment of the chimpanzee AluYh3a1 element DC7 and the AluSq element present at the orthologous position in the human genome. Diagnostic positions for AluYh3a1 are shown in blue boxes, the characteristic deletion of AluSq is shown in a red box. This case represents an example of complete gene conversion replacing an Alu element from an old subfamily with one from a younger subfamily.

Figure 4

Alignment of chimpanzee AluYh3a1 element DC39 and the human orthologue. A partial gene conversion event has introduced diagnostic mutations into the human element, shown in blue boxes. A transversion mutation is shared between orthologues outside the putative gene conversion tract, shown in the red box. It is possible that one of these elements has been introduced by complete gene conversion, with subsequent parallel mutation at position 25.

Figure 5

Alignment of AluYh3a3 elements in the chimpanzee, with the AluYh3a1 consensus. A progressive accumulation of mutations can be seen in the putative master gene, DB3, supporting the master gene model of proliferation of this subfamily.

Figure 6

Progressive accumulation of mutations in the AluYh3a3 master gene. The master gene model of proliferation accounts for the sharing of mutations by several groups of elements in the AluYh3a3 subfamily in chimpanzees. A complete gene conversion event appears to have inactivated the master gene along the human lineage.

Figure 7

Inferred relationships between AluYi6 derivative subfamilies. Diagnostic mutations for each putative subfamily are shown in each box. The copy numbers of each of these putative subfamilies are listed in table 2. Blue dotted lines indicate the presence of a subfamily in chimpanzees. The mutation shown in red is a back mutation to the ancestral nucleotide at an AluYi6 diagnostic site.