SVA Elements: A Hominid-specific Retroposon Family

SVA is a composite repetitive element named after its main components, SINE, VNTR and Alu. We have identified 2762 SVA elements from the human genome draft sequence. Genomic distribution analysis indicates that the SVA elements are enriched in G+C-rich regions but have no preferences for inter- or intragenic regions. A phylogenetic analysis of the elements resulted in the recovery of six subfamilies that were named SVA_A to SVA_F. The composition, age and genomic distribution of the subfamilies have been examined. Subfamily age estimates based upon nucleotide divergence indicate that the expansion of four SVA subfamilies (SVA_A, SVA_B, SVA_C and SVA_D) began before the divergence of human, chimpanzee and gorilla, while subfamilies SVA_E and SVA_F are restricted to the human lineage. A survey of human genomic diversity associated with SVA_E and SVA_F subfamily members showed insertion polymorphism frequencies of 37.5% and 27.6%, respectively. In addition, we examined the amplification dynamics of SVA elements throughout the primate order and traced their origin back to the beginnings of hominid primate evolution, approximately 18 to 25 million years ago. This makes SVA elements the youngest family of retroposons in the primate order.

Introduction

Transposons and transposon-like repetitive elements collectively occupy about 44% of the human genome. Alu and L1 (long interspersed element-1) elements account for ∼30% of the genome sequence and are the most abundant transposable elements in humans,¹ while human endogenous retroviruses (HERVs) represent another ∼1% of the human genome. In addition to the major retrotransposon families, there are smaller families of transposons such as SVA, which are receiving increased attention lately due to their recent retrotransposition activity in the human genome.2, 3

The SVA element was originally named SINE-R, with the R indicating its retroviral origin.⁴ In 1994, Shen et al. identified a new composite retroposon when they studied the structure of the RP gene.⁵ This new retroposon consisted of the SINE-R element together with a stretch of sequence that shares sequence similarity with Alu sequences. Thus, it was named “SVA” after its main components, SINE, VNTR and Alu.⁵

SVA elements contain the hallmarks of retrotransposons, in that they are flanked by target site duplications (TSDs), terminate in a poly(A) tail and they are occasionally truncated and inverted during their integration into the genome.² In addition, they can transduce 3′ sequences during their movement. Therefore, it has been proposed that SVA elements are non-autonomous retrotransposons that are mobilized by L1 encoded proteins in trans.²

SVA elements remain active in the human genome, as demonstrated by their involvement in the creation of various diseases. To date, at least four diseases have been reported related to SVA insertions.2, 6, 7, 8, 9, 10 This makes SVA the third known category of retrotransposons currently expanding in the human lineage, along with L1 and Alu elements.11, 12

To assess the distribution and impact of SVA elements in the human genome, we examined all the SVA elements in the human genome reference sequence.¹ Six SVA subfamilies were identified and characterized. For the two human-specific subfamilies, the associated insertion presence/absence human genomic diversity was analyzed. Furthermore, we traced the origin of the entire SVA family back to the beginning of the hominid primate radiation and determined the copy number of SVA elements in different non-human primate genomes. The overall distribution of SVA elements showed a significant correlation with genomic G+C content and gene density.