May 6, 2024
Gene duplication is a fundamental evolutionary mechanism that contributes to biological complexity and diversity (Fortna et al., 2004). Traditionally, research has focused on the duplication of gene sequences (Zhang, 1914). However, evidence suggests that the duplication of regulatory elements may also play a significant role in the evolution of genomic functions (Teichmann and Babu, 2004; Hallin and Landry, 2019). In this work, the evolution of regulatory relationships belonging to gene-specific-substructures in a GRN are modeled. In the model, a network grows from an initial configuration by repeatedly choosing a random gene to duplicate. The likelihood that the regulatory relationships associated with the selected gene are retained through duplication is determined by a vector of probabilities. Occurrences of gene-family-specific substructures are counted under the gene duplication model. In this thesis, gene-family-specific substructures are referred to as subnetwork motifs. These subnetwork motifs are motivated by network motifs which are patterns of interconnections that recur more often in a specialized network than in a random network (Milo et al., 2002). Subnetwork motifs differ from network motifs in the way that subnetwork motifs are instances of gene-family-specific substructures while network motifs are isomorphic substructures. These subnetwork motifs are counted under Full and Partial Duplication, which differ in the way in which regulation relationships are inherited. Full duplication occurs when all regulatory links are inherited at each duplication step, and Partial Duplication occurs when regulation inheritance varies at each duplication step. Moments for the number of occurrences of subnetwork motifs are determined in each model. The results presented offer a method for discovering subnetwork motifs that are significant in a GRN under gene duplication.
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April 28, 2007
Background: Duplication of genes is important for evolution of molecular networks. Many authors have therefore considered gene duplication as a driving force in shaping the topology of molecular networks. In particular it has been noted that growth via duplication would act as an implicit way of preferential attachment, and thereby provide the observed broad degree distributions of molecular networks. Results: We extend current models of gene duplication and rewiring by inc...
December 19, 2017
The biological processes of cellular decision making and differentiation involve a plethora of signalling pathways and gene regulatory circuits. These networks, in their turn, exhibit a multitude of motifs playing crucial parts in regulating network activity. Here, we compare the topological placement of motifs in gene regulatory and signalling networks and find that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.
August 31, 2002
Are biological networks different from other large complex networks? Both large biological and non-biological networks exhibit power-law graphs (number of nodes with degree k, N(k) ~ k-b) yet the exponents, b, fall into different ranges. This may be because duplication of the information in the genome is a dominant evolutionary force in shaping biological networks (like gene regulatory networks and protein-protein interaction networks), and is fundamentally different from the...
October 4, 2005
We study a class of growth algorithms for directed graphs that are candidate models for the evolution of genetic regulatory networks. The algorithms involve partial duplication of nodes and their links, together with innovation of new links, allowing for the possibility that input and output links from a newly created node may have different probabilities of survival. We find some counterintuitive trends as parameters are varied, including the broadening of indegree distribut...
Developing and maintaining life requires a lot of computation. This is done by gene regulatory networks. But we have little understanding of how this computation is organized. I show that there is a direct correspondence between the structural and functional building blocks of regulatory networks, which I call regulatory motifs. I derive a simple bound on the range of function that these motifs can perform, in terms of the local network structure. I prove that this range is a...
January 12, 2018
Gene regulatory networks are powerful abstractions of biological systems. Since the advent of high-throughput measurement technologies in biology in the late 90s, reconstructing the structure of such networks has been a central computational problem in systems biology. While the problem is certainly not solved in its entirety, considerable progress has been made in the last two decades, with mature tools now available. This chapter aims to provide an introduction to the basic...
July 26, 2021
Research shows that gene duplication followed by either repurposing or removal of duplicated genes is an important contributor to evolution of gene and protein interaction networks. We aim to identify which characteristics of a network can arise through this process, and which must have been produced in a different way. To model the network evolution, we postulate vertex duplication and edge deletion as evolutionary operations on graphs. Using the novel concept of an ancestra...
July 27, 2021
In this paper, we conduct theoretical analyses on inferring the structure of gene regulatory networks. Depending on the experimental method and data type, the inference problem is classified into 20 different scenarios. For each scenario, we discuss the problem that with enough data, under what assumptions, what can be inferred about the structure. For scenarios that have been covered in the literature, we provide a brief review. For scenarios that have not been covered in li...
November 30, 2010
Over the past decade, a number of researchers in systems biology have sought to relate the function of biological systems to their network-level descriptions -- lists of the most important players and the pairwise interactions between them. Both for large networks (in which statistical analysis is often framed in terms of the abundance of repeated small subgraphs) and for small networks which can be analyzed in greater detail (or even synthesized in vivo and subjected to expe...
January 29, 2020
Analysis of the structure of biological networks often uses statistical tests to establish the over-representation of motifs, which are thought to be important building blocks of such networks, related to their biological functions. However, there is disagreement as to the statistical significance of these motifs, and there are potential problems with standard methods for estimating this significance. Exponential random graph models (ERGMs) are a class of statistical model th...