Simple repeat evolution includes dramatic primary sequence changes that conserve folding potential

Riley, Donald E.; Jeon, Joon Seong; Krieger, John N.

doi:10.1016/j.bbrc.2007.01.200

Cited by 8 publications

(10 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Coding microsatellites may be subject to purifying selection as they might be important for protein structure and protein–protein interactions (Hancock and Simon 2005) or to indirect selection as a source of adaptive evolution (Wren et al 2000; Fondon and Garner 2004; Riley and Krieger 2009a). In 3′-UTRs, some microsatellites have been shown to be selected for their folding potential rather than their primary sequence (Riley et al 2007). Although it is not clear what the function of most nonexonic microsatellites is, there is clear evidence that at least some are acting as regulators of gene expression (Kashi and King 2006; Vinces et al 2009), suggesting that noncoding microsatellites could also be indirectly selected for mutability.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, further investigation is needed to tease out structural changes among orthologous microsatellites, for example, how compound structures arise in genomes (Kofler et al 2008), whether there are motif changes (Riley et al 2007; Riley and Krieger 2009b), and whether there are interspecies and intraspecies variations in length and/or mutability (Laidlaw et al 2007; Kelkar et al 2008). Moreover, as a consequence of the complexity and heterogeneity of microsatellite mutational dynamics, there is to date no theoretical development to estimate the life expectancy, thus the turnover, of microsatellites above the species level (Stephan and Kim 1998).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Conservation of Human Microsatellites across 450 Million Years of Evolution

Buschiazzo

Gemmell

2010

Genome Biology and Evolution

View full text Add to dashboard Cite

The sequencing and comparison of vertebrate genomes have enabled the identification of widely conserved genomic elements. Chief among these are genes and cis-regulatory regions, which are often under selective constraints that promote their retention in related organisms. The conservation of elements that either lack function or whose functions are yet to be ascribed has been relatively little investigated. In particular, microsatellites, a class of highly polymorphic repetitive sequences considered by most to be neutrally evolving junk DNA that is too labile to be maintained in distant species, have not been comprehensively studied in a comparative genomic framework. Here, we used the UCSC alignment of the human genome against those of 11 mammalian and five nonmammalian vertebrates to identify and examine the extent of conservation of human microsatellites in vertebrate genomes. Out of 696,016 microsatellites found in human sequences, 85.39% were conserved in at least one other species, whereas 28.65% and 5.98% were found in at least one and three nonprimate species, respectively. An exponential decline of microsatellite conservation with increasing evolutionary time, a comparable distribution of conserved versus nonconserved microsatellites in the human genome, and a positive correlation between microsatellite conservation and overall sequence conservation, all suggest that most microsatellites are only maintained in genomes by chance, although exceptionally conserved human microsatellites were also found in distant mammals and other vertebrates. Our findings provide the first comprehensive survey of microsatellite conservation across deep evolutionary timescales, in this case 450 Myr of vertebrate evolution, and provide new tools for the identification of functional conserved microsatellites, the development of cross-species microsatellite markers and the study of microsatellite evolution above the species level.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Conservation of Human Microsatellites across 450 Million Years of Evolution

Buschiazzo

Gemmell

2010

Genome Biology and Evolution

View full text Add to dashboard Cite

show abstract

“…One explanation for such a threshold level may be a selection pressure to retain stabile conformations. Such a selection pressure has been suggested to be important for preserving folding potential in repeated di-nucleotides [21,36] and tri-nucleotides [37]. In this respect, nothing is currently known for pentanucleotides.…”

Section: Discussionmentioning

confidence: 99%

“…Mutation patterns may also depend on the genomic context such as the particular location on a chromosome and functional potential of the transcribed product [9,16-18], as well as the effectiveness of mismatch repair enzymes [19,20]. Moreover, mutation rates in microsatellites are also affected by stabilization patterns and potential secondary structures [13,21]. …”

Section: Introductionmentioning

confidence: 99%

Microsatellite evolution: Mutations, sequence variation, and homoplasy in the hypervariable avian microsatellite locus HrU10

et al. 2008

View full text Add to dashboard Cite

BackgroundMicrosatellites are frequently used genetic markers in a wide range of applications, primarily due to their high length polymorphism levels that can easily be genotyped by fragment length analysis. However, the mode of microsatellite evolution is yet not fully understood, and the role of interrupting motifs for the stability of microsatellites remains to be explored in more detail. Here we present a sequence analysis of mutation events and a description of the structure of repeated regions in the hypervariable, pentanucleotide microsatellite locus HrU10 in barn swallows (Hirundo rustica) and tree swallows (Tachycineta bicolor).ResultsIn a large-scale parentage analysis in barn swallows and tree swallows, broods were screened for mutations at the HrU10 locus. In 41 cases in the barn swallows and 15 cases in the tree swallows, mutations corresponding to the loss or gain of one or two repeat units were detected. The parent and mutant offspring alleles were sequenced for 33 of these instances (26 in barn swallows and 7 in tree swallows). Replication slippage was considered the most likely mutational process. We tested the hypothesis that HrU10, a microsatellite with a wide allele size range, has an increased probability of introductions of interruptive motifs (IMs) with increasing length of the repeated region. Indeed, the number and length of the IMs was strongly positively correlated with the total length of the microsatellite. However, there was no significant correlation with the length of the longest stretch of perfectly repeated units, indicating a threshold level for the maximum length of perfectly repeated pentanucleotide motifs in stable HrU10 alleles. The combination of sequence and pedigree data revealed that 15 barn swallow mutations (58%) produced alleles that were size homoplasic to other alleles in the data set.ConclusionOur results give further insights into the mode of microsatellite evolution, and support the assumption of increased slippage rate with increased microsatellite length and a stabilizing effect of interrupting motifs for microsatellite regions consisting of perfect repeats. In addition, the observed extent of size homoplasy may impose a general caution against using hypervariable microsatellites in genetic diversity measures when alleles are identified by fragment length analysis only.

show abstract

“…Unlike repeats which disrupt the reading frame, and have a strong effect on replication and transcription stability[31], the tri-nucleotide repeats might be constrained in a different way. It seems that repeats located in the promoter region[32] have a stronger influence on transcription than do AARs, even those near the transcription start.…”

Section: Discussionmentioning

confidence: 99%

The expansion of amino-acid repeats is not associated to adaptive evolution in mammalian genes

2009

View full text Add to dashboard Cite

BackgroundThe expansion of amino acid repeats is determined by a high mutation rate and can be increased or limited by selection. It has been suggested that recent expansions could be associated with the potential of adaptation to new environments. In this work, we quantify the strength of this association, as well as the contribution of potential confounding factors.ResultsMammalian positively selected genes have accumulated more recent amino acid repeats than other mammalian genes. However, we found little support for an accelerated evolutionary rate as the main driver for the expansion of amino acid repeats. The most significant predictors of amino acid repeats are gene function and GC content. There is no correlation with expression level.ConclusionsOur analyses show that amino acid repeat expansions are causally independent from protein adaptive evolution in mammalian genomes. Relaxed purifying selection or positive selection do not associate with more or more recent amino acid repeats. Their occurrence is slightly favoured by the sequence context but mainly determined by the molecular function of the gene.

show abstract

Simple repeat evolution includes dramatic primary sequence changes that conserve folding potential

Cited by 8 publications

References 23 publications

Conservation of Human Microsatellites across 450 Million Years of Evolution

Conservation of Human Microsatellites across 450 Million Years of Evolution

Microsatellite evolution: Mutations, sequence variation, and homoplasy in the hypervariable avian microsatellite locus HrU10

The expansion of amino-acid repeats is not associated to adaptive evolution in mammalian genes

Contact Info

Product

Resources

About