Integration as Evolutionary Signature
Following on from the previous article 'Last of the MTHFRs: Compatibility as an Evolutionary Signature', this article looks further into integration and the expansion of biology within humanity itself
EVOLUTIONBIOLOGYMETABOLISM
Alexandra Chambers
8/10/20265 min read
Life has not expanded only by producing novelty from within itself. Again and again, biological systems have acquired, preserved or incorporated difference - sometimes from divergent members of the same species, sometimes from entirely different organisms, and sometimes from viruses or bacteria that once existed outside the organism altogether. The result is a striking evolutionary pattern: Difference is encountered, some of it disappears, and some remains separate but becomes mutually functional. Some becomes fully incorporated into the genome. In extraordinary cases, something that was once an entirely independent organism becomes an indispensable part of the cell itself.
Human biology itself contains extraordinarily old variation. As explored in previous articles, modern populations retain genomic material inherited through admixture with Neanderthals, Denisovans and potentially other archaic human populations. Much introgressed material was subsequently removed, while other segments persisted. The important observation is that some divergent biological information entered another genomic architecture and remained sufficiently compatible with reproduction, development and biological function to continue for tens of thousands of years.
Persistence tells us that integration occurred, but evolution has integrated far more than human diversity. The principle becomes much more striking when we move beyond different human lineages. Some of the most fundamental systems in human biology originated in organisms that were once completely external to our ancestors. The clearest example is the mitochondrion.
Mitochondria descend from bacteria that entered into an ancient cellular relationship more than a billion years ago. What began as an encounter between distinct forms of life eventually became such profound interdependence that the former bacterium became part of the cellular architecture of complex life. Most of its former genetic independence disappeared. Some genetic material was transferred to the host nuclear genome. Metabolic systems became interdependent. Communication evolved between mitochondrial and nuclear genomes. Eventually the relationship became inseparable.
Humans do not just coexist with descendants of those ancient bacteria; we are built around them. Almost every metabolically active cell in the human body depends upon an ancient biological integration between organisms that were once distinct. That changes the way biological individuality can be understood. The human organism contains the legacy of successful relationships with other biology. Evolution can transform invasion into regulation and foreign biology can become inherited biology.
Not all successful biological integration requires genomic incorporation. The human microbiome demonstrates ecological integration. Bacteria within the gut remain separate organisms with their own genomes, yet human physiology operates in continuous biochemical exchange with them. Microbial communities metabolise dietary substrates human enzymes cannot process alone. They produce compounds that interact with intestinal epithelial cells, immune pathways and metabolic systems. They participate in the development and regulation of the biological environment in which human cells function. The microbes have not become human cells. Yet neither can human physiology be completely understood as though they were irrelevant outsiders.
This gives us several levels of biological integration:
A bacterium can remain distinct while becoming metabolically embedded in our ecology.
A viral sequence can enter the genome and become regulatory machinery.
A protein can become part of placental development.
A bacterium can become an organelle.
Different biological entities can therefore remain separate, become partially integrated, become genetically incorporated or ultimately become almost inseparable from the organism itself. Integration exists on a continuum. Evolutionary expansion has repeatedly involved the acquisition of capacities that did not originate inside the existing biological system.
Mitochondria brought metabolic capacities.
Microorganisms contribute biochemical capacities.
Archaic admixture introduced genomic variation from divergent human populations.
Ancient polymorphisms preserved different solutions within the same continuing lineage.
The recurring pattern is:
Difference → encounter → interaction → accommodation → integration → expanded biological capacity
This does not mean every biological encounter is beneficial. Microbes can become pathogenic, and biological incompatibility exists everywhere. That is precisely why successful integration matters. The evolutionary significance lies not in difference alone but in difference that can become functionally incorporated without destroying the system that receives it.
Diversity within compatibility becomes a mechanism through which biological systems can expand. This principle does not stop at the boundary of the human body. Every organism evolved within an ecology. Food, microorganisms, sunlight, minerals, plants, animals, seasonal cycles and innumerable biochemical exposures formed the environment within which human regulatory systems developed.
Human biology did not evolve separately from that ecology; it evolved through it. Biological regulation is continuously responsive to environmental information. This becomes especially important when considering mitochondria and the epigenome. Mitochondrial metabolism generates and regulates molecules required by enzymes involved in chromatin modification. Changes in mitochondrial metabolism can therefore influence histone modification, DNA methylation, chromatin accessibility and gene expression. The mitochondrion - itself the product of an ancient bacterial integration - participates in the signalling through which the nuclear genome responds to cellular conditions. This produces an extraordinary evolutionary continuity:
Ancient environmental biology became integrated into the cell, and that integrated system now helps regulate how the genome responds to the environment.
What happens when the environment changes faster than biology?
Industrial and technological environments have introduced enormous numbers of exposures that were absent, rare or structurally different throughout most of human evolutionary history. That does not justify a simplistic division in which everything natural is beneficial and everything synthetic is harmful. This framework is a place for nuance where context is rigorously examined. Natural and organic substances can be profoundly toxic, and synthetic interventions can be lifesaving.
The biologically important distinction may instead be evolutionary familiarity and integration.
Human regulatory systems developed within particular ecological relationships. Those systems now encounter combinations, concentrations, timings and types of exposure for which there may have been little evolutionary opportunity for accommodation.
This creates the possibility of evolutionary mismatch at the level of biological regulation.
Mitochondria may be particularly revealing. Their bacterial ancestry means that some compounds designed to interfere with bacterial biology can also interfere with mitochondrial processes. More broadly, mitochondrial dysfunction can alter redox signalling, metabolite availability, inflammatory pathways and nuclear gene regulation. The consequences therefore would not remain confined to the mitochondrion.
A plausible biological chain would be:
Environmental disruption → mitochondrial disturbance → altered metabolism and signalling → altered epigenetic regulation → altered gene expression → changed cellular and organismal phenotype
The epigenome is one of the interfaces through which environmental experience becomes biological regulation. Disrupting that interface does not necessarily alter the DNA sequence itself, but it can alter how that sequence is used. This creates a tension at the centre of modern human biology. Our fundamental systems are products of deep evolutionary integration, but the environment surrounding those systems is changing rapidly. If biological complexity was constructed through long periods of successful accommodation between organisms and ecology, then increasingly novel environments may place stress upon regulatory relationships that took immense evolutionary timescales to develop. The question therefore becomes larger than whether individual substances are toxic.
What happens when the rate and character of environmental change exceed the capacity of ancient integrated biological systems to remain coherent? The answer may be disease. Disruption of the relationship between genome, mitochondria, microbiome, immune system, metabolism, epigenome and ecology. Many apparently separate biological disturbances become different manifestations of lost integration. This is why I distinguish biological persistence from what I would describe as organic evolutionary expansion.
Persistence alone tells us that something continues. It does not tell us what the continuing system is becoming. Biological history demonstrates something richer than survival. Life has repeatedly expanded through the successful integration of difference. The surrounding ecosystem became inseparable from the regulatory biology of the organism living within it. Evolution, viewed through this lens, is therefore not merely the replacement of old biology by new biology. Much of its extraordinary complexity has come from carrying biological history forward, integrating difference and building new capacity upon what remains compatible.
This leads to the central proposition: Diversity provides biological possibility. Compatibility allows that diversity to remain. Integration converts it into biological capacity. This may be the most fundamental mechanism of organic evolution.
The concern for modern humanity is not technology itself, nor the existence of synthetic biology or synthetic environments. However, If the ecological and biochemical conditions supporting our oldest regulatory systems are progressively disrupted, humanity could become increasingly technologically capable while simultaneously becoming biologically less integrated. That would not represent the end of adaptation; humans may continue adapting. However, adaptation to a deteriorating biological environment is not biological expansion, or provolution as described in the Divergent Genomics framework.
It is the opposite.
Image: Richard Altmann, Die Elementarorganismen und ihre Beziehungen zu den Zellen (1890), Tafel I. Wellcome Collection. Public Domain.