In Defence of Lamarck: an Application of Epigenetics

 by Natalie Moras

Statue of Jean-Baptiste Lamarck, Paris

During GCSE Biology, students are told that Lamarck’s proposal of passing down characteristics developed within one’s lifetime was false, but is this a lie?

We were taught that Darwinian evolution is more accurate instead. For Darwinian evolution by natural selection to occur, three requirements must be met:

1. Traits must vary amongst organisms within the population (if all the organisms had identical traits, then there would be nothing for natural selection to differentially act upon);

2. These variable traits must be heritable;

3. These variable heritable traits must lead to increases in reproduction.

If these three requirements are met, evolution by natural selection must occur. The heritable variations that lead to reduced reproduction will decrease in frequency over time, whereas those that increase reproduction will increase in frequency over time. The way traits are selected as 'positive' for reproduction is if they are well suited to the surrounding environment the organism is within.

In 1802, Jean Baptiste Lamark proposed that the environment in which an organism is placed modifies its traits and that these modifications can be passed onto offspring. 

Let’s compare the two ideals. A Darwinian natural selection hypothesis proposes that a trait that is heritable varies between individuals and those with the variations of the trait that hold the most reproductive advantages, by enabling the highest success in offspring production, passing these traits down through the alleles that code for the trait. A Lamarkian hypothesis proposes that the individuals who developed a certain trait within their lifetimes to be even more beneficial to survival, would eventually produce offspring that would inherit the advantages of the trait that was improved during the parent’s lifetime, and that this could be passed down further to future generations. We were taught that acquired characteristics do not change sequences of DNA and thus cannot be inherited by future generations; therefore rendering Lamark’s theory invalid. 

Introducing epigenetics: referring to changes in organisms caused by modification of gene regulation and expression rather than alteration of the genetic code itself.

Hence, the environment cannot change the genes we have but we now know it can alter our epigenetics. This can involve the methylation of DNA and the modification of histone proteins. The modifications are attached to DNA, and do not change the sequence of DNA building blocks. These can alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression. These processes are crucial to normal development and differentiation of distinct cell lineages in adult organisms. They can be modified by exogenous influences and can thereby contribute to environmental alterations of phenotype. In particular, epigenetic programming has a crucial role in the regulation of pluripotency genes, which become inactivated during differentiation.

Because epigenetic changes help determine whether genes are turned on or off, they influence the production of proteins in cells. This regulation helps ensure that each cell produces only proteins that are necessary for its function. In DNA methylation, methyl groups are attached to the position of cytosine on genes. When these methyl groups are present on a gene, that gene is silenced. Therefore, no protein is produced from that gene. Histone modification differs. Histones are structural proteins that DNA wraps around, giving chromosomes their shape. Histones are modifiable by the addition or removal of chemical groups (like methyl groups or acetyl groups). This affects how tightly the DNA wraps around the histones and therefore whether a gene can be expressed. 

It is important to recognise that in the epigenetic process errors can occur which ultimately lead to disadvantages in organisms. If the wrong gene is present or there is a failure to add a chemical group to a particular gene or histone, there can be abnormal gene activity or inactivity. A common cause of genetic disorders is altered gene activity (including that which is caused by epigenetic errors). Various conditions have been found to correlate to epigenetic errors: cancers, metabolic disorders and degenerative disorders. 

Dias and Ressler carried out experiments to show the potential power of trans generational epigenetic changes. Specifically how trauma can affect behaviour and neuroanatomy in later generations. This was done in a mice experiment.

Kerry Ressler and Brian Dias decided to study epigenetic inheritance in laboratory mice conditioned to fear the smell of acetophenone (a chemical with a seventh comparable to cherries and almonds). They wafted the scent around a small chamber of male mice while administering electric shocks to them. Eventually, they associated the smell with pain. They even shuddered in the presence of acetophenone when they were not shocked. When their offspring were presented with acetophenone they exhibited an increased sensitivity to it, like their fathers, despite never coming into contact with the smell or ever being shocked - they shuddered more markedly than descendants of mice that had been conditioned to be startled by a different smell or that had gone through no conditioning at all. Additionally, a third generation of mice (conceived by IVF with sperm from males sensitised to acetophenone) also displayed the same reaction when exposed to the chemical despite never being shocked before.

The mice that were sensitised to acetophenone, as well as their descendants, had more neurons that produce a receptor protein known to detect acetophenone compared with control mice and their progeny. The structures that receive signals from the neurons that detect the chemical and send smell signals to other parts of the brain (such as those involved in processing fear) were also larger in these mice.

It was proposed that DNA methylation explains the inherited effect. In the fearful mice, the acetophenone-sensing gene of sperm cells had fewer methylation marks, which could have led to greater expression of the odorant-receptor gene during development. Ressler furthers this in stating that sperm cells themselves express odorant receptor proteins, and that some odorants find their way into the bloodstream, offering a potential mechanism, as do small, blood-borne fragments of RNA (microRNAs) that control gene expression.

However, the mice's reactions and their link to DNA is not as convincing for all experts. Timothy Bestor, who studied epigenetic modifications as a molecular biologist at Columbia University in New York, states, "The claims they make are so extreme they kind of violate the principle that extraordinary claims require extraordinary proof." This is because he finds that DNA methylation is unlikely to influence the production of the protein that detects acetophenone. He finds that most genes that are known to be controlled by methylation have modifications in the promoter region, which precedes the gene in the DNA sequence but in contrast the acetophenone-detecting gene lacks the presence of nucleotides in the promoter that can be methylated.

Thus, transgenerational epigenetic changes could be an important mechanism to prime subsequent generations to have a particular sensitivity to features of the environment that could likely be important during their lifespans. This can thus affect their survival and reproduction, by improving the likelihood of both. However, this may not be the case in every scenario.

In conclusion, epigenetics can affect the variation of traits and these traits can be heritable. If these traits prove to be advantageous by causing subsequent generations to possess a particular sensitivity to important environmental cues (as Dias and Ressler displayed), then epigenetic modifications satisfy the three criteria for Darwinian evolution by natural selection to occur. The changes may not be as durable as cumulative changes in allele frequencies but there is a role for epigenetics in the evolutionary process, in a perspective called ‘Neo-Lamarckism’.