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GRN Kernels, Character Identity Networks (ChIN), and Deep Homology

GRN Kernels, Character Identity Networks (ChIN), and Deep Homology

The kernel concept

The development of embryos in different species seems to follow similar patterns. For example, we can observe that human embryos have a tail around 30-35 weeks into the pregnancy (Figure 12).

Many species are visually close to indistinguishable from each other in the early stages of development (Video 1).

The observed similarities in embryo development have led to different various hypotheses and theories. One notable approach uses the kernel concept. This concept treats genomes as a blueprint for embryo development.

Video 1. Embryonic development - embryogenesis

The kernel concept uses four separate gene regulatory components: 1. The kernel, 2. plug-ins, 3. input-output (I/O) switches, and 4. differentiation gene batteries (Figure 13).

Kernels are the core regulatory subunits that define the central fundamental developmental patterns. They are resistant to changes and rewiring and are therefore evolutionarily strongly conserved.

The strongly conserved kernels may be responsible for the stable animal body plans that we can track back over 500 million years.

In Figure 14, we can see an example of a kernel that regulates the development of endomesoderm and is conserved in both Sea urchins and Starfishes.

Figure 13. Schematic illustration of a gene regulatory network (GRN) kernel, plug-ins, I/O switches, and gene differentiation batteries.
Figure 13. Schematic illustration of a gene regulatory network (GRN) kernel, plug-ins, I/O switches, and gene differentiation batteries.
Figure 14. Gene regulatory network (GRN) kernel regulating the development of endomesoderm. The kernel is conserved in Starfish and Sea urchin.
Figure 14. Gene regulatory network (GRN) kernel regulating the development of endomesoderm. The kernel is conserved in Starfish and Sea urchin.

Plug-ins are similarly, as kernels, small structurally conserved regulatory sub-circuitries. However, they do not specify the development of body parts.

Plug-ins are insertable modules into various gene regulatory schemes and, for example, affecting a limited set of transcription factors.

Input/output (I/O) switches regulate various other sub-networks and are the subject of evolutionary changes in the embryonal development processes. In many cases, the changes can be trivial, such as the size of body parts.

The determination of a body part size may only require a specific way to connect a body part patterning gene with cell cycle genes. A few examples are Drosophila haltere wing patterning, hox gene specifying the vertebrate morphology, and the fore-wing vs. hind-wing patterning.

Differentiation gene batteries are the executive branch consisting of specific groups of protein-coding genes. The gene batteries produce distinct proteins needed by each cell type and do not regulate any other genes or exercise other controls.

They are active at the end of the developmental processes and controlled by receiving cell-type-specific signals. The expression of specific differentiation gene batteries is a terminal process of differentiation.

The differentiation gene batteries may evolve by changes in their coding sequences, loosing, and gaining genes.

The character identity network (ChIN) concept

Before we dive into the character identity network, we need to define two things: 1. Character identity, and 2. character state. It is essential to understand the difference between these because they represent two separate evolutionary relationships.

While the character identity remains the same, it can appear in different forms as character states. Butterflies appendices have developed into four wings used for flying (Figure 15).

In cranefly, the other pair of appendices have developed into halteres, that insects use to sense the body position during a flight (Figure 16). Beetles' one of the appendix pairs have developed into wing covers, elytra (Figure 16).

An organ with one character identity can appear in different architectures, i.e., character states, as in the cases of the appendices of butterflies, craneflies, and beetles.

Figure 15. A butterfly has four wings, fore wings, and hind wings.
Figure 16. In a cranefly, the second pair of appendices developed as halteres, the two club-shaped organs. (Source: Nono64, CC BY-SA 3.0 )
Figure 17. In beetles, the second pair of appendices developed as wing covers (elytra). (Source: Clinton & Charles Robertson from Del Rio, Texas & College Station, TX, USA - Ladybird Beetle Taking Flight, CC BY-SA 2.0 )

A core gene regulatory networks cause a developmental individualization of different body parts by utilizing a variety of effector genes.

These core gene regulatory networks are character identity networks (ChINs) that preserve the identity of a character but allow a set of effector genes to produce a variety of character states. Different realizations, i.e., different phenotypes of the same body part.

Character identity networks, as the name says, preserve the identity of an organ or a body part. This way, the hind wings of the butterfly (Figure 15) and the halteres of the cranefly (Figure 16) are homologous because the origin of each individualized body part is the same in both species (Figure 18).

The ChIN concept has three organizational levels: 1. positional information through cell-cell signaling, 2. ChINs, and 3. realizer genes (Figure 18.)

1. Cell-cell signaling gives positional information to ChINs and activates them at specific locations. The signaling genes can be variable between species (Figure 18a).

2. The ChIN networks, activated by the cell-cell signaling, are well conserved in various species. The ChINs consist mostly of transcription factors, transcription co-factors, and long non-coding RNAs. ChINs specify the character identity and can regulate different realizer genes as target genes in various species, but do not necessarily determine the set of realizer genes (Figure 18b).

3. The realizer genes are genes that produce proteins and enzymes for a specific cell type, the workforce of the cells. This set of genes bear similarity to the differentiation gene batteries in the kernel concept. The disassociation of ChINs from the realizer genes explains how the phenotype or a character state can be a separate entity from the character identity (Figure 18c).

In Figure 19, is a real-world example of a ChIN of hepatocytes. Notice the positive feedback loop, which is characteristic in all ChINs. For the ChINs to work, all the transcription factors within a ChIN need to co-operate.

The necessity of the transcription factor co-operation may also be a reason for them to be well conserved. A single change in one of the factors is likely to damage the co-operation; Thus, keeping the ChINs conserved and preserving the character identity.

Charles Darwin well explained how a multitude of structures in various organisms arises through descent with modifications. However, how unique structures and phenotypes arise has been under debate for a long time. The character identity network (ChIN) concept could explain the rise of unique structures by an introduction of unique ChINs.

Figure 18. An illustration of the concept of character identity networks, consisting of three levels: a) Cell-cell signaling, positional information, b) character identity network, a conserved identity, and c) realizer genes that do the actual work in each cell type.
Figure 19. Cell identity network (ChIN) of hepatocytes and the realizer genes.

The Deep Homology Concept

Shubin, Tabin, and Carroll coined the term deep homology in 1997. Deep homology term covers conserved gene networks in the developmental differentiation processes in separate species.

We can see an example of deep homology in Figure 20, which illustrates the expression patterns of hox genes, specifying the body plans. On the left, the expression patterns are color-coded for C. elegans, D. melanogaster, B. floridae, M. musculus, and human. On the right, the chromosomal organization of the hox genes.

Figure 21 shows a phylogeny-based classification of the hox protein-coding genes for D. melanogaster and M. musculus with a hypothetical common ancestor. The color-coding is the same as in Figure 20.

Both Kernel and ChIN are deep homology concepts, each attempting to describe the mechanisms and categorize them.

Figure 20. Left: The expression patterns of hox genes. Right: The chromosomal organization of the hox genes. source: Hueber SD, Weiller GF, Djordjevic MA, Frickey T (2010)
Figure 21. A phylogeny-based classification of the hox protein-coding genes. source: Hueber SD, Weiller GF, Djordjevic MA, Frickey T (2010)

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