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A DNA circuit that records molecular events.

ABSTRACT: Characterizing the relative onset time, strength, and duration of molecular signals is critical for understanding the operation of signal transduction and genetic regulatory networks. However, detecting multiple such molecules as they are produced and then quickly consumed is challenging. A MER can encode information about transient molecular events as stable DNA sequences and are amenable to downstream sequencing or other analysis. Here, we report the development of a de novo molecular event recorder that processes information using a strand displacement reaction network and encodes the information using the primer exchange reaction, which can be decoded and quantified by DNA sequencing. The event recorder was able to classify the order at which different molecular signals appeared in time with 88% accuracy, the concentrations with 100% accuracy, and the duration with 75% accuracy. This simultaneous and highly programmable multiparameter recording could enable the large-scale deciphering of molecular events such as within dynamic reaction environments, living cells, or tissues.

SUBMITTER: Zhang M

PROVIDER: S-EPMC10997190 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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A DNA circuit that records molecular events.

Zhang Mingzhi M Yancey Colin C Zhang Chao C Wang Junyan J Ma Qian Q Yang Linlin L Schulman Rebecca R Han Da D Tan Weihong W

Science advances 20240405 14

Characterizing the relative onset time, strength, and duration of molecular signals is critical for understanding the operation of signal transduction and genetic regulatory networks. However, detecting multiple such molecules as they are produced and then quickly consumed is challenging. A MER can encode information about transient molecular events as stable DNA sequences and are amenable to downstream sequencing or other analysis. Here, we report the development of a de novo molecular event re ...[more]

PMID: 38578999

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Project description:Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC) genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies.Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model). However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used to explore the genetic history of human populations, and that their analysis allows a more thorough investigation of human MHC molecular evolution.

Dataset Information

A DNA circuit that records molecular events.

Publications

A DNA circuit that records molecular events.

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