Short interspersed elements (SINEs) are a major source of canine genomic diversity

Abstract

SINEs are retrotransposons that have enjoyed remarkable reproductive success during the course of mammalian evolution, and have played a major role in shaping mammalian genomes. Previously, an analysis of survey-sequence data from an individual dog (a poodle) indicated that canine genomes harbor a high frequency of alleles that differ only by the absence or presence of a SINEC_Cf repeat. Comparison of this survey-sequence data with a draft genome sequence of a distinct dog (a boxer) has confirmed this prediction, and revealed the chromosomal coordinates for >10,000 loci that are bimorphic for SINEC_Cf insertions. Analysis of SINE insertion sites from the genomes of nine additional dogs indicates that 3%-5% are absent from either the poodle or boxer genome sequences—suggesting that an additional 10,000 bimorphic loci could be readily identified in the general dog population. We describe a methodology that can be used to identify these loci, and could be adapted to exploit these bimorphic loci for genotyping purposes. Approximately half of all annotated canine genes contain SINEC_Cf repeats, and these elements are occasionally transcribed. When transcribed in the antisense orientation, they provide splice acceptor sites that can result in incorporation of novel exons. The high frequency of bimorphic SINE insertions in the dog population is predicted to provide numerous examples of allele-specific transcription patterns that will be valuable for the study of differential gene expression among multiple dog breeds.

Transposable elements and an epigenetic basis for punctuated equilibria

“…The canine genome is replete with SINEs, and dog breeds display remarkable diversity in insertions of the SINE_Cf family, with an estimated 10,000 loci bimorphic for insertions. (112) Even more striking is TE-based genomic divergence between inbred mouse strains. In a study of five strains, 10,000 genomic variants were identified, 85% of which were attributable to recent mobilization of predominantly LINE-1 TEs.…”

The birth of new exons: Mechanisms and evolutionary consequences

“…Similarly, 65% of new exons in rodents are derived from repetitive elements (Zhang and Chasin 2006). In the canine genome, the SINEC_Cf repeats were shown to contribute multiple exons through exonization (Wang and Kirkness 2005). New exons originating from repeat sequences were also identified in cow and zebrafish genomes (Alekseyenko et al 2007).…”

“…Following the sequencing of the human genome as well as millions of expressed sequence tags (ESTs), hundreds of additional such events were found (Nekrutenko and Li 2001;Sorek et al 2002). With the accumulation of many recently sequenced vertebrate genomes, reports on exonizations become more abundant and now include thousands of new exons in rodents , dogs (Wang and Kirkness 2005), and multiple other vertebrate genomes such as cow and fish (Alekseyenko et al 2007;Krull et al 2007). …”

Genome sequence, comparative analysis and haplotype structure of the domestic dog

“…Of ,87,000 young SINEC_Cf elements (defined by low divergence from the consensus sequence), nearly 8% are heterozygous within the draft genome sequence of the boxer. Moreover, comparison of the boxer and standard poodle genome sequences reveals more than 10,000 insertion sites that are bimorphic, with thousands more certain to be segregating in the dog population 16,39 . In contrast, the number of polymorphic SINE insertions in the human genome is estimated to be fewer than 1,000 (ref.…”

“…SINE insertions can be mutagenic through direct disruption of coding regions or through indirect effects on regulation and processing of messenger RNAs 39 . Such SINE insertions have already been shown to be responsible for two diseases in dog: narcolepsy and centronuclear myopathy 41,42 .…”