24 July 2024
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Understanding Gene Regulatory Divergence in Species

Genes play a crucial role in determining the characteristics of living organisms, from physical appearance to susceptibility to diseases. However, the expression of genes, controlled by regulatory elements in the DNA, can vary significantly between species. A recent study sheds light on the mechanisms of gene regulatory divergence between closely related animal species, uncovering the complex interplay of cis and trans regulatory elements in driving these differences.

Unraveling the Complexity of Gene Regulation

Traditionally, differences between species have been attributed to changes in the DNA sequence (cis), which directly impact the structure or function of proteins. However, the study by molecular biologist Emily Hodges and her colleagues highlights that alterations in gene expression can also stem from changes in the regulatory elements of the DNA. These regulatory elements, such as enhancers, act as switches that control the expression of target genes.

Enhancer function can be modified by DNA sequence changes within a single enhancer (cis) or by alterations in the cellular environment that affect multiple enhancers (trans). Transcription factors, which are mobile proteins that regulate gene expression, can bind to enhancers on different chromosomes, influencing gene expression across the genome. Understanding the balance between cis and trans regulatory mechanisms is essential for comprehending the evolution of gene regulation in different species.

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Insights from the Study

The research conducted by the labs of Emily Hodges and Tony Capra utilized a cutting-edge technique called ATAC-STARR-seq to dissect the contributions of cis and trans regulatory mechanisms to gene regulatory divergence between humans and rhesus macaques. By examining the effects of DNA sequence changes and cellular environment variations on gene expression, the researchers identified a significant role for trans changes in driving gene regulatory activity between species.

Contrary to previous beliefs that cis regulatory changes predominantly drive regulatory divergence, the study revealed that trans regulatory changes play a critical role in shaping gene expression differences between species. This groundbreaking finding challenges existing paradigms in the field and underscores the importance of considering the impact of cellular environment on gene regulation evolution.

Implications for Human Health and Disease

The implications of understanding gene regulatory divergence extend beyond evolutionary biology to human health and disease. Emily Hodges plans to expand the study’s findings to investigate how cis and trans regulatory mechanisms contribute to variations in human disease risk. In diseases like cancer, where genetic mutations, epigenetic modifications, and cellular environment interactions play a significant role, unraveling the complexities of gene regulation can provide valuable insights into disease mechanisms and potential therapeutic strategies.

The study highlights the intricate relationship between cis and trans regulatory elements in driving gene regulatory divergence between species. By unraveling the mechanisms underlying these differences, researchers are paving the way for a deeper understanding of genetic evolution, human health, and disease susceptibility.

Links to additional Resources:

1. www.nature.com 2. www.science.org 3. www.cell.com

Related Wikipedia Articles

Topics: Gene regulatory divergence, DNA regulatory elements, Transcription factors

Trans-regulatory element
Trans-regulatory elements (TRE) are DNA sequences encoding upstream regulators (ie. trans-acting factors), which may modify or regulate the expression of distant genes. Trans-acting factors interact with cis-regulatory elements to regulate gene expression. TRE mediates expression profiles of a large number of genes via trans-acting factors. While TRE mutations affect gene...
Read more: Trans-regulatory element

Cis-regulatory element
Cis-regulatory elements (CREs) or cis-regulatory modules (CRMs) are regions of non-coding DNA which regulate the transcription of neighboring genes. CREs are vital components of genetic regulatory networks, which in turn control morphogenesis, the development of anatomy, and other aspects of embryonic development, studied in evolutionary developmental biology. CREs are found...
Read more: Cis-regulatory element

Transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure...
Read more: Transcription factor

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