An exceptionally long CA-repeat in the core promoter of SCGB2B2 links with the evolution of apes and Old World monkeys

Nikkhah, M Javan; Rezazadeh, Maryam; Khorshid, Hamid Reza Khorram; Biglarian, Akbar; Ohadi, Mina

doi:10.1016/j.gene.2015.09.070

Cited by 26 publications

(16 citation statements)

References 39 publications

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“…Promoter CA-repeats are associated with inter-and intra-species variations in gene expression, quantitative traits and disease phenotypes [8,31,32]. The human NHLH2 gene "exceptionally long" CA-repeat is located at position -4 of the TSS of an intron-less transcript, and is the longest CA-repeat detected across human proteincoding core promoter intervals.…”

Section: Discussionmentioning

confidence: 99%

“…The human NHLH2 gene "exceptionally long" CA-repeat is located at position -4 of the TSS of an intron-less transcript, and is the longest CA-repeat detected across human proteincoding core promoter intervals. Only one other gene, namely SCGB2B2, contains a functional CA-repeat of similar length [3], whose expansion links to the evolution of apes and Old World monkeys [8]. Interestingly, evolutionary analysis of the NHLH2 CA-repeat revealed that this STR became longer and more complex from nonprimates to basic primates, the New/Old World monkeys, and great apes, reaching maximum length in human.…”

Section: Discussionmentioning

confidence: 99%

“…1). The NHLH2 CA-repeat, along with the CA-repeat in the SCGB2B2 gene, is the longest human CA-STR identified in a human protein-coding gene core promoter [8].…”

Section: Introductionmentioning

confidence: 99%

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Natural Selection at the NHLH2 Core Promoter Exceptionally Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset Neurocognitive Disorder

Afshar¹,

Adelirad²,

Kowsari³

et al. 2020

Gerontology

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Background: Approximately 2% of the human core promoter short tandem repeats (STRs) reach lengths of ≥6 repeats, which may in part be a result of adaptive evolutionary processes and natural selection. A single-exon transcript of the human nescient helix loop helix 2 (NHLH2) gene is flanked by the longest CA-repeat detected in a human protein-coding gene core promoter (Ensembl transcript ID: ENST00000369506.1). NHLH2 is involved in several biological and pathological pathways, such as motivated exercise, obesity, and diabetes. Methods: The allele and genotype distribution of the NHLH2 CA-repeat were investigated by sequencing in 655 Iranian subjects, consisting of late-onset neurocognitive disorder (NCD) as a clinical entity (n = 290) and matched controls (n = 365). The evolutionary trend of the CA-repeat was also studied across vertebrates. Results: The allele range was between 9 and 25 repeats in the NCD cases, and 12 and 24 repeats in the controls. At the frequency of 0.56, the 21-repeat allele was the predominant allele in the controls. While the 21-repeat was also the predominant allele in the NCD patients, we detected significant decline of the frequency (p < 0.0001) and homozygosity (p < 0.006) of this allele in this group. Furthermore, 12 genotypes were detected across 16 patients (5.5% of the entire NCD sample) and not in the controls (disease-only genotypes; p < 0.0003), consisting of at least one extreme allele. The extreme alleles were at 9, 12, 13, 18, and 19 repeats (extreme short end), and 23, 24, and 25 repeats (extreme long end), and their frequencies ranged between 0.001 and 0.04. The frequency of the 21-repeat allele significantly dropped to 0.09 in the disease-only genotype compartment (p <

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Natural Selection at the NHLH2 Core Promoter Exceptionally Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset Neurocognitive Disorder

Afshar¹,

Adelirad²,

Kowsari³

et al. 2020

Gerontology

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“…Sonay et al . studied STRs in both human and nonhuman great ape genomes and showed that STRs contribute significantly to the diversity and divergence of gene expression among species13181920. These findings indicate that STRs are essential elements in molecular evolution and underscore their functional potential.…”

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confidence: 87%

The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model

Chen

Huang

et al. 2016

Sci Rep

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Functional short tandem repeats (STR) are polymorphic in the population, and the number of repeats regulates the expression of nearby genes (known as expression STR, eSTR). STR in IGF1 promoter has been extensively studied for its association with IGF1 concentration in blood and various clinical traits and represents an important eSTR. We previously used an in-vitro luciferase reporter model to examine the interaction between STRs and SNPs in IGF1 promoter. Here, we further explored the mechanism how the number of repeats of the STR regulates gene transcription. An inverse correlation between the number of repeats and the extent of transactivation was found in a haplotype consisting of three promoter SNPs (C-STR-T-T). We showed that these adjacent SNPs located outside the STR were required for the STR to function as eSTR. The C allele of rs35767 provides a binding site for CCAAT/enhancer-binding-protein δ (C/EBPD), which is essential for the gradational transactivation property of eSTR and FOXA3 may also be involved. Therefore, we propose a mechanism in which the gradational transactivation by the eSTR is caused by the interaction of one or more transcriptional complexes located outside the STR, rather than by direct binding to a repeat motif of the STR.

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“…Genome-scale findings of the evolutionary trend of a number of STRs has begun to unfold their implications in respect with speciation and species-specific characteristics/phenotypes (Yuan et al 2018;Emamalizadeh et al 2017;Abe and Gemmell 2016;Bushehri et al 2016;Namdar-Aligoodarzi et al 2016;Nikkhah et al 2016;Bilgin Sonay et al 2015;Rezazadeh et al 2014;Khademi et al 2017;Mohammadparast et al 2014;Ohadi et al 2012;King et al 2012). The hypermutable nature of STRs and their large unascertained reservoir of functionality make them an ideal source of evolutionary adaptation, speciation, and disease (Hannan et al 2018;Bagshaw et al 2017;Press et al 2017;Ohadi et al2015;Valipour et al 2013;Heidari et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Link Between Short tandem Repeats and Translation Initiation Site Selection

Arabfard

Kavousi

Delbari

et al. 2018

Preprint

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Recent work in yeast and humans suggest that evolutionary divergence in cis-regulatory sequences impact translation initiation sites (TISs). Cis-elements can also affect the efficacy and amount of protein synthesis. Despite their vast biological implication, the landscape and relevance of short tandem repeats (STRs)/microsatellites to the human protein-coding gene TISs remain largely unknown. Here we characterized the STR distribution at the 120 bp cDNA sequence upstream of all annotated human protein-coding gene TISs based on the Ensembl database. Furthermore, we performed a comparative genomics study of all annotated orthologous TIS-flanking sequences across 47 vertebrate species (755,956 transcripts), aimed at identifying human-specific STRs in this interval. We also hypothesized that STRs may be used as genetic codes for the initiation of translation. The initial five amino acid sequences (excluding the initial methionine) that were flanked by STRs in human were BLASTed against the initial orthologous five amino acids in other vertebrate species (2,025, in order to compare the number of events in which human-specific and non-specific STRs occurred with homologous and non-homologous TISs (i.e. ≥50% and <50% similarity of the five amino acids). We characterized human-specific STRs and a bias of this compartment in comparison to the overall (human-specific and non-specific) distribution of STRs (Mann Whitney p=1.4 x 10 -11 ). We also found significant enrichment of non-homologous TISs flanked by human-specific STRs (p<0.00001). In conclusion, our data indicate a link between STRs and TIS selection, which is supported by differential evolution of the human-specific STRs in the TIS upstream flanking sequence.

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An exceptionally long CA-repeat in the core promoter of SCGB2B2 links with the evolution of apes and Old World monkeys

Cited by 26 publications

References 39 publications

Natural Selection at the NHLH2 Core Promoter Exceptionally Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset Neurocognitive Disorder

Natural Selection at the NHLH2 Core Promoter Exceptionally Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset Neurocognitive Disorder

The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model

Link Between Short tandem Repeats and Translation Initiation Site Selection

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