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Multiplexed Analysis of Retinal Gene Expression and Chromatin Accessibility Using scRNA-Seq and scATAC-Seq

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Apprehending multicellularity: regulatory networks, genomics, and evolution.

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¹National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA. aravind@ncbi.nlm.nih.gov

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Summary

Biological regulatory networks evolve through historical processes, not engineering. Comparative genomics reveals how gene changes and non-coding DNA shape these networks, influencing organism complexity.

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Area of Science:

Evolutionary biology
Genomics
Systems biology

Background:

The genomic revolution offers insights into the architecture of biological regulatory networks.
Understanding these networks is crucial as they arise from historical contingencies, not deliberate design.
A network perspective combined with evolutionary data illuminates how life processes are shaped.

Purpose of the Study:

To provide a synthetic overview of the natural history of regulatory networks in multicellular organisms.
To explore the evolutionary forces that have shaped the architecture of these networks.
To examine how novel innovations and pre-existing components assemble into complex regulatory systems.

Main Methods:

Application of graph theory to understand regulatory network organization.
Analysis of comparative genomics data to identify effects of gene duplication, loss, and non-coding DNA.
Case study of the conserved Notch subnetwork across Metazoa.

Main Results:

Gene lineage-specific expansions, gene loss, and non-coding DNA significantly impact network architecture.
Interactions between transcription factor expansions and cis-regulatory elements contribute to morphological complexity.
The Notch subnetwork exemplifies evolutionary assembly from new and repurposed components.

Conclusions:

Regulatory networks are shaped by evolutionary history and contingency.
Comparative genomics and network analysis are powerful tools for understanding biological system evolution.
Complex regulatory systems like the Notch pathway evolve through incremental addition and modification of components.