Do microRNA cause Lamarckian evolution?

I was perusing Pubmed Centeral to look for something interesting to read while waiting in between interviews yesterday and I came across this article titled, “Lamarckian evolution explains human brain evolution and psychiatric disorders.” Intriguing concept. Fun illustrative example and thought exercise. My short answer is: Only by an extraordinarily loose interpretation of Lamarckian evolution and by narrowing the scope of natural selection unnecessarily, and if a just-so set of experimental observations proves that brain plasticity leads to epigenetic or RNA changes in testes and ovaries. So I think the arguments of the paper are weak, but still worth thinking about for anyone interested in evolution of the human brain and its quirks. To look at this, let’s review the basics.

Mechanism for transmitting acquired traits. Activity and experience-dependent changes to brain cause exosomes containing microRNA released into the circulation; which is then passed on to offspring, influencing brain development and behavior/cognition. In my opinion, implausible mechanism of evolution.
Mechanism for transmitting acquired traits. Activity and experience-dependent changes to brain cause exosomes containing microRNA released into the circulation; which is then passed on to offspring, influencing brain development and behavior/cognition. In my opinion, this is an implausible mechanism of evolution of the human brain.

Evolution is the change in inherited characteristics over successive generations. It occurs at all levels of biological organization. At the species level over geologic history, this is  sufficient change that populations are so different they cannot produce viable offspring. At the population level, it can be the proportions of types of a gene (e.g., genes coding for eye color — changes in the proportion of blue vs. brown, etc.); emergence and loss of new genes in a population (e.g., via gene duplication & mutation giving rise to new functionality or deletion of genes; or even duplication, deletion, merging of whole chromosomes). At generational/family level, it could be bacteria with antibiotic resistance plasmids being transmitted, or even viruses (e.g., HIV) acquiring drug resistance mutations.

Natural Selection (Mendel, Darwin, Huxley) is a theory about the mechanism of evolution and, in its modern incarnation, it posits that mutations, deletions, duplications in a genome are passed on to successive generations. For each generation, more offspring are produced than there are resources to survive. Therefore, those that survive to reproduce are those with the set of genes which give rise to the “fittest” phenotype. Variations on this are mass extinction events making spaces for new niches & speciation, founder effects in which a small number of individuals colonize an isolated area and generations arising from the isolated population drift from the original population (e.g., on an island).

Heritability of Acquired Characteristics (Lamarck) is a theory about the mechanism of evolution in which a parent’s use of a particular trait generate adaptations which are passed on to the next generation. A classic example is the giraffe. A giraffe-like animal stretched its neck to reach branches, and its offspring had long necks as a result of the parent stretching, and so on for many generations so that now they are born with super long necks. In humans, this would be, for example a blacksmith uses his arms and gets strong, so he will have strong offspring who will grow up to be blacksmiths. Or an educated nobleman will have children who are born with inherent wisdom as a result of his parents’ education. You can see how this would be problematic. Also, there is no mechanism by which this would happen.

This paper by Guy Barry argues that Lamarckian evolution explains the expanded neocortex in humans and also psychiatric disorders. He makes several claims, links them together, and makes a few predictions. So let’s look at the claims.

First, the human brain is plastic. That is, it changes in structure and organization in an activity-dependent manner and in response to the environment. This is most definitely true. However, I think he over-emphasizes the brain’s ability to change in an activity dependent manner, stating, “Other tissues are concomitantly undergoing adaptive responses, albeit at normally lower levels …” I think this grossly understates the ability of nearly all tissues to change in response to activity. The changes in vasculature alone during intense and prolonged cardiovascular exercise is huge, generating hundreds or thousands of new capillaries all over the body, near the surface of the skin to help regulate temperature, within muscles to deliver oxygen and remove carbon dioxide, in the lungs to increase the surface area for gas exchange. This is not done because the blood vessel “thinks,” it’s a pre-programmed biochemical response whose in structures are embedded in the DNA (of every cell). In response to lower O2 and higher CO2, along with other chemicals like NO, reduced ATP availability, and even increased mechanical torsion on the cell. A biochemical cascade is started in a vascular endothelia cell causing it to divide, and the cells around it to divide, and form a tube, branching out from an existing one, making a new capillary. Nearly every cell type in every tissue undergoes activity-dependent adaptations and changes. In the brain, synapses are formed and broken … thousands and thousands of them are constantly made and broken down, strengthened, weakened; new neurites are extended to form new connections; and new brain cells are born, migrate, and (possibly) integrate from the subgranular zone of the hippocampus. During experiences, like, say … a stressful event, hormones are released, memories are encoded, associations between objects and emotions are strengthened. The hormones do affect the whole body as well as the brain. This is true. But I think he’s assigning unjustified importance to the brain’s adaptability over other organs and tissues.

Second, brain cells, which have undergone activity-dependent changes, transmit information to testes and ovaries which then pass this information on to the next generation. There are a few plausible (but improbable) mechanisms by which this could happen.

  1. Experiences like chronic stress, starvation, injury, or trauma, cause hormonal changes which lead to epigenetic changes in sperm and eggs.  These epigenetic changes include methylation of DNA or modification of histones.  These are actually chemical processes that change the shape of the DNA structure locally around specific genes, which then affects how the genes that are later transcribed. The problem with this is only the methylation patterns will persist after several cellular generations, and so may affect very early developmental patterns (including possibly the brain, and there is some supporting evidence in schizophrenia for this to happen), are unlikely to be further transmitted. The histone modifications won’t even persist for a cellular generation because during DNA replication, all the DNA is exposed and during mitosis, all the DNA is tightly packaged in histones; the modifications of the histones aren’t preserved between the parent and daughter strands.
  2. Small, non-coding RNAs (microRNA), are secreted in extracellular microsomes (exosomes) which circulate in the blood. The microRNA in the exosomes somehow makes its way to the testes and ovaries, and transmits activity-dependent (or experience-dependent) information which persists to the next generation. This is interesting, but there’s no evidence for it. There is evidence for microRNA in exosomes circulating in the blood. And there’s evidence of microRNA in exosomes in the brain, where the donor cell is an astrocytes and the recipient is a neuron. But, as far as I am aware, exosomes containing microRNA originating from the brain has never been observed in circulation. This would be potentially ground-breaking, if it were found.

The final claim is that the transmitted information from the experience (e.g., “stress” leading to methylation) causes brain changes in the offspring during development, and this persists in all subsequent generations. This has also never been shown. Stressful situations, and conditioned fear to odor in pregnant mice has been shown to be transmitted to her litter. But this has never been shown in either a non-pregnant state or to occur in transmitting information from the male parent to offspring. I think this is a case of the mother’s womb acting as an environment to the developing offspring. Secondly, there is no mechanism by which it would be transmitted to subsequent generations. Thirdly, the “stressful” conditions which are transmitted to the offspring do not confer expanded neocortex and frontal lobe to the offspring, it transmits psychiatric and metabolic abnormalities.

The prediction made by in this paper is that these weaknesses will be addressed. We will find exosomes originating in the brain which transfer microRNA to either testes or ovaries. The content and number of them will vary by activity and experience.

Only by a view that Lamarckian evolution is limited to influencing phenotype of one generation could this view be true. Also, if the traits are transmitted to the next generation. Let’s assume the prediction comes true, natural selection will still act on the offspring. If an acquired trait (e.g., post traumatic stress disorder) is transmitted via microRNA or epigenetics, the selective pressure of the environment will still act on whether or not the offspring reproduces.

All in all, this is an interesting thought exercise. While the idea is pretty far out there and doesn’t conform to what is known about microRNA, exosomes, the brain, and evolution…. it is still an interesting thought exercise to consider how and why ideas might fall flat.

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