Short tandem repeats, segmental duplications, gene deletion, and genomic instability in a rapidly diversified immune gene family

Abstract

BackgroundGenomic regions with repetitive sequences are considered unstable and prone to swift DNA diversification processes. A highly diverse immune gene family of the sea urchin (Strongylocentrotus purpuratus), called Sp185/333, is composed of clustered genes with similar sequence as well as several types of repeats ranging in size from short tandem repeats (STRs) to large segmental duplications. This repetitive structure may have been the basis for the incorrect assembly of this gene family in the sea urchin genome sequence. Consequently, we have resolved the structure of the family and profiled the members by sequencing selected BAC clones using Illumina and PacBio approaches.ResultsBAC insert assemblies identified 15 predicted genes that are organized into three clusters. Two of the gene clusters have almost identical flanking regions, suggesting that they may be non-matching allelic clusters residing at the same genomic locus. GA STRs surround all genes and appear in large stretches at locations of putatively deleted genes. GAT STRs are positioned at the edges of segmental duplications that include a subset of the genes. The unique locations of the STRs suggest their involvement in gene deletions and segmental duplications. Genomic profiling of the Sp185/333 gene diversity in 10 sea urchins shows that no gene repertoires are shared among individuals indicating a very high gene diversification rate for this family.ConclusionsThe repetitive genomic structure of the Sp185/333 family that includes STRs in strategic locations may serve as platform for a controlled mechanism which regulates the processes of gene recombination, gene conversion, duplication and deletion. The outcome is genomic instability and allelic mismatches, which may further drive the swift diversification of the Sp185/333 gene family that may improve the immune fitness of the species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3241-x) contains supplementary material, which is available to authorized users.

Xq22 deletions and correlation with distinct neurological disease traits in females: Further evidence for a contiguous gene syndrome

“…Such motifs have been associated with genomic instability in several previous studies (Bacolla & Wells, ; Boyer, Grgurevic, Cazaux, & Hoffmann, ; Chen et al, ; Madireddy & Gerhardt, ; Oren et al, ; Wang & Vasquez, ; Wells, ; Wojciechowska, Napierala, Larson, & Wells, ; Zhao, Bacolla, Wang, & Vasquez, ). In particular, STRs, and IRs (including palindromic or potential cruciform forming sequences) have been found to be enriched near recurrent and nonrecurrent deletion CNV breakpoints (Akgun et al, ; Chen et al, ; Oren et al, ). We investigated RepX‐i1010 and the GI‐hotspot for seven non‐B DNA motifs including G‐Quadruplex forming sequences, STRs, A‐phased repeats, mirror repeats (MR), IRs, direct repeats (DRs), and Z‐DNA forming sequences (Cer et al, ; Wells, ).…”

Stable recombinant production of codon‐scrambled lubricin and mucin in human cells

“…The fidelity of nearly all DNA processing steps can be compromised by slippage and other errors linked to repetitive sequences (López Castel, Cleary, & Pearson, 2010). Consequently, repeats can mutate by addition or loss of their unit nucleotide sequence up to 100000 times more frequently than point mutations in nonrepetitive regions (Oren et al, 2016). The variation in tandem repeat numbers for Muc1 and other mucins in humans and mammals provides an evolutionary argument that these genomic DNAs may be mutational hotspots (Gemayel, Vinces, Legendre, & Verstrepen, 2010).…”

Multitasking Immune Sp185/333 Protein, rSpTransformer-E1, and Its Recombinant Fragments Undergo Secondary Structural Transformation upon Binding Targets

“…10). First, the genes make up a family of tightly clustered genes that appear to undergo duplications and deletions (9,23) plus some preliminary evidence of recombination within the tandem repeats in the second exon ( Fig. 1A) (24).…”