Deeply conserved chordate noncoding sequences preserve genome synteny but do not drive gene duplicate retention

ABSTRACT By high-resolution, restriction mapping of mitochondrial DNAs purified from 112 human individuals, we have identified 14 length variants caused by small additions and deletions (from about 6 to 14 base pairs in length). Three of the 14 length differences are due to mutations at two locations within the D loop, whereas the remaining 11 occur at seven sites that are probably within other noncoding sequences and at junctions between coding sequences. In five of the nine regions of length polymorphism, there is a sequence of five cytosines in a row, this sequence being comparatively rare in coding DNA. Phylogenetic analysis indicates that, in most of the polymorphic regions, a given length mutation has arisen several times independently in different human lineages. The average rate at which length mutations have been arising and surviving in the human species is estimated to be many times higher for noncoding mtDNA than for noncoding nuclear DNA. The mystery of why vertebrate mtDNA is more prone than nuclear DNA to evolve by point mutation is now compounded by the discovery of a similar bias toward rapid evolution by length mutation.

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Molecular characteristics of S-RNase alleles as the determinant of self-incompatibility in the style of Fragaria viridis

Horticulture Research ◽

10.1038/s41438-021-00623-x ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Jianke Du ◽

Chunfeng Ge ◽

Tingting Li ◽

Sanhong Wang ◽

Zhihong Gao ◽

...

Keyword(s):

Diploid Species ◽

The Self ◽

Molecular Characteristics ◽

Self Incompatibility ◽

Intraspecific Hybridization ◽

Noncoding Sequences ◽

Family Analysis ◽

The Family ◽

Genotype Identification ◽

Rnase T2

AbstractStrawberry (Fragaria spp.) is a member of the Rosoideae subfamily in the family Rosaceae. The self-incompatibility (SI) of some diploid species is a key agronomic trait that acts as a basic pollination barrier; however, the genetic mechanism underlying SI control in strawberry remains unclear. Two candidate S-RNases (Sa- and Sb-RNase) identified in the transcriptome of the styles of the self-incompatible Fragaria viridis 42 were confirmed to be SI determinants at the S locus following genotype identification and intraspecific hybridization using selfing progenies. Whole-genome collinearity and RNase T2 family analysis revealed that only an S locus exists in Fragaria; however, none of the compatible species contained S-RNase. Although the results of interspecific hybridization experiments showed that F. viridis (SI) styles could accept pollen from F. mandshurica (self-compatible), the reciprocal cross was incompatible. Sa and Sb-RNase contain large introns, and their noncoding sequences (promotors and introns) can be transcribed into long noncoding RNAs (lncRNAs). Overall, the genus Fragaria exhibits S-RNase-based gametophytic SI, and S-RNase loss occurs at the S locus of compatible germplasms. In addition, a type of SI-independent unilateral incompatibility exists between compatible and incompatible Fragaria species. Furthermore, the large introns and neighboring lncRNAs in S-RNase in Fragaria could offer clues about S-RNase expression strategies.

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Functional mapping of androgen receptor enhancer activity

Genome Biology ◽

10.1186/s13059-021-02339-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Chia-Chi Flora Huang ◽

Shreyas Lingadahalli ◽

Tunc Morova ◽

Dogancan Ozturan ◽

Eugene Hu ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Binding Sites ◽

Gene Promoters ◽

Strongly Correlated ◽

Enhancer Activity ◽

Drive Gene Expression ◽

In Vitro Cell Lines ◽

Drive Gene

Abstract Background Androgen receptor (AR) is critical to the initiation, growth, and progression of prostate cancer. Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there are 10–100× more binding sites than differentially expressed genes. It is unclear how or if these excess binding sites impact gene transcription. Results To characterize the regulatory logic of AR-mediated transcription, we generated a locus-specific map of enhancer activity by functionally testing all common clinical AR binding sites with Self-Transcribing Active Regulatory Regions sequencing (STARRseq). Only 7% of AR binding sites displayed androgen-dependent enhancer activity. Instead, the vast majority of AR binding sites were either inactive or constitutively active enhancers. These annotations strongly correlated with enhancer-associated features of both in vitro cell lines and clinical prostate cancer samples. Evaluating the effect of each enhancer class on transcription, we found that AR-regulated enhancers frequently interact with promoters and form central chromosomal loops that are required for transcription. Somatic mutations of these critical AR-regulated enhancers often impact enhancer activity. Conclusions Using a functional map of AR enhancer activity, we demonstrated that AR-regulated enhancers act as a regulatory hub that increases interactions with other AR binding sites and gene promoters.

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Conserved noncoding sequences are selectively constrained and not mutation cold spots

Nature Genetics ◽

10.1038/ng1710 ◽

2005 ◽

Vol 38 (2) ◽

pp. 223-227 ◽

Cited By ~ 147

Author(s):

Jared A Drake ◽

Christine Bird ◽

James Nemesh ◽

Daryl J Thomas ◽

Christopher Newton-Cheh ◽

...

Keyword(s):

Noncoding Sequences ◽

Conserved Noncoding Sequences ◽

Cold Spots

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Copy-Number Variations, Noncoding Sequences, and Human Phenotypes

Annual Review of Genomics and Human Genetics ◽

10.1146/annurev-genom-082410-101404 ◽

2011 ◽

Vol 12 (1) ◽

pp. 53-72 ◽

Cited By ~ 40

Author(s):

Eva Klopocki ◽

Stefan Mundlos

Keyword(s):

Copy Number ◽

Copy Number Variations ◽

Noncoding Sequences

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Conserved Noncoding Sequences Boost ADR1 and SP1 Regulated Human Swiprosin-1 Promoter Activity

Scientific Reports ◽

10.1038/s41598-018-34802-z ◽

2018 ◽

Vol 8 (1) ◽

Author(s):

Ramesh P. Thylur ◽

Sung Yong Ahn ◽

Eunhea Jung ◽

Chang-Duk Jun ◽

Young-Min Hyun

Keyword(s):

Promoter Activity ◽

Noncoding Sequences ◽

Conserved Noncoding Sequences

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Identification of a DNA segment that is necessary and sufficient for alpha-specific gene control in Saccharomyces cerevisiae: implications for regulation of alpha-specific and a-specific genes.

Molecular and Cellular Biology ◽

10.1128/mcb.8.1.309 ◽

1988 ◽

Vol 8 (1) ◽

pp. 309-320 ◽

Cited By ~ 40

Author(s):

E E Jarvis ◽

D C Hagen ◽

G F Sprague

Keyword(s):

Saccharomyces Cerevisiae ◽

Binding Site ◽

Transcript Level ◽

Cell Types ◽

Specific Gene ◽

Alpha Cells ◽

Transcription Activator ◽

Noncoding Sequences ◽

Necessary And Sufficient ◽

Activation Sequence

STE3 mRNA is present only in Saccharomyces cerevisiae alpha cells, not in a or a/alpha cells, and the transcript level increases about fivefold when cells are treated with a-factor mating pheromone. Deletions in the 5' noncoding region of STE3 defined a 43-base-pair (bp) upstream activation sequence (UAS) that can impart both modes of regulation to a CYC1-lacZ fusion when substituted for the native CYC1 UAS. UAS activity required the alpha 1 product of MAT alpha, which is known to be required for transcription of alpha-specific genes. A chromosomal deletion that removed only 14 bp of the STE3 UAS reduced STE3 transcript levels 50- to 100-fold, indicating that the UAS is essential for expression. The STE3 UAS shares a 26-bp homology with the 5' noncoding sequences of the only other known alpha-specific genes, MF alpha 1 and MF alpha 2. We view the homology as having two components--a nearly palindromic 16-bp "P box" and an adjacent 10-bp "Q box." A synthetic STE3 P box was inactive as a UAS; a perfect palindrome P box was active in all three cell types. We propose that the P box is the binding site for a transcription activator, but that alpha 1 acting via the Q box is required for this activator to bind to the imperfect P boxes of alpha-specific genes. Versions of the P box are also found upstream of a-specific genes, within the binding sites of the repressor alpha 2 encoded by MAT alpha. Thus, the products of MAT alpha may render gene expression alpha or a-specific by controlling access of the same transcription activator to its binding site, the P box.

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