Darwin's theory of evolution by natural selection is incomplete without the contribution of antihero Lamarck
Much of modern biology is based on the theory of Charles Darwin about evolution as a process of natural selection, when nature chooses the strongest and most adapted organisms to reproduce, increase population and survive. This process is also called adaptation, and adaptive are those traits that help the body to survive better than others. As new modifications of organisms change and take root, species appear and develop. In the 1850s, when Darwin described the engine of natural selection, the underlying molecular mechanisms were not yet known. But advances in genetics and molecular biology of the last century have outlined the basic tenets of modern neo-Darwinian theory of how evolution works: DNA sequences mutate randomly,and those organisms whose DNA is best adapted to the environment multiply and dominate. These species prevail until environmental conditions begin to change and the engine of evolution starts up again.
But if we assume that other molecular mechanisms also play a role in the development of species, then this explanation of evolution turns out to be incomplete. The problem with Darwin's theory is that while species develop more adaptive properties (called phenotypes in biology), the rate at which random mutations occur in DNA sequences is too low to explain many of the observed changes. Scientists well aware of this problem suggest a number of compensatory genetic mechanisms: gene drift, when serious genetic changes occur within a small group of organisms, or epistasis, when one set of genes suppresses another. And these are just two of many examples.
But even with these mechanisms in mind, the rate of genetic mutation among complex organisms such as humans is significantly lower than the rate of change in a range of traits from metabolic regulation to disease resistance. The rapid manifestation of a variety of traits is difficult to explain only by the methods of classical genetics and neo-Darwinian theory. To quote the eminent evolutionary biologist Jonathan BL Bard, paraphrasing TS Eliot: "A shadow fell between phenotype and genotype."
The problematic points of Darwin's theory go beyond the theory of evolution and extend into other areas of biology and biomedicine. For example, if our traits are determined by heredity, then why do identical twins with the same set of genes tend to have different diseases? And why is it that only a small number (often less than 1%) of those suffering from specific diseases have common genetic mutations? If the rate of mutations is random and uniform, then why did the proportion of many diseases increase tenfold in just a couple of decades? Why do hundreds of types of environmental pollution change the circumstances of the onset of diseases, but not the DNA sequence of the diseased? In evolution and biomedicine, the rate of formation of deviations from phenotypic traits is much higher than the rate of genetic changes and mutations, but why?
Some answers can be found in the ideas of Jean-Baptiste Lamarck, published 50 years before the publication of Darwin's work. Lamarck's theory, long gone to the dustbin of history, argued, among other things, that "the environment modifies properties that are then inherited by new generations." Lamarck was professor of invertebrate zoology at the National Museum of Natural History in Paris, and in the late 18th and early 19th centuries he studied a variety of organisms, including insects and worms. It was he who introduced the words "biology" and "invertebrates" into the scientific lexicon, and he was also the author of several books on biology, invertebrates and evolution. Despite his distinguished scientific career, Lamarck, with his blasphemous evolutionary ideas, was denied by many contemporaries, as well as scientists for the next 200 years.
Initially, Lamarck was condemned as a religious heretic, and nowadays his name is remembered only as a joke, because of the conservatism of science, and especially Darwin's inviolable theory of evolution. At the end of his scientific journey, Lamarck himself changed his beliefs: even without confirmation from the field of molecular biology, he saw that random changes cannot become a full proof of his theory.
The question is this: if genetic mutations are not only affected by natural selection, then what are the molecular forces that shape the full set of changes in traits needed to complete the work of natural selection? One of the clues was found almost a century after Darwin presented his theory. In 1953, when James Watson and Francis Crick were unraveling the mysteries of DNA and the double helix, evolutionary biologist Conrad Waddington of the University of Edinburgh reported that external chemical stimuli or temperature changes during embryonic development could cause the appearance of various variants of the wing structure in Drosophila. The changes that the scientist's actions caused in organisms of one generation were subsequently passed on to the offspring. To explain this mechanism of rapid change, Waddington coined the modern term epigenetics. It should be noted that Waddington was aware of the significance of his discovery to the theory of evolution, even before Watson and Crick deduced data on the structure of DNA. Changes in the wing structure of one generation of Drosophila confirmed the original ideas of the heretic Lamarck. It turned out that the environment is able to directly influence the characteristics of the organism.that the environment can directly affect the characteristics of the organism.that the environment can directly affect the characteristics of the organism.
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Although Waddington described the general role of epigenetics, he knew no more about molecular elements and mechanisms than Darwin or Lamarck. But the deeper molecular biology decodes the way life functions, the more meaningful Waddington's - and Lamarck's concepts become. Indeed, the vast majority of environmental factors cannot directly affect the molecular sequence of DNA, but they regulate many epigenetic mechanisms that control the functions of DNA: they trigger or quench gene expression, dictate the ways of expression in cells of proteins - the product of our genes.
Today, there is a precise definition of epigenetics - it is a set of molecular factors that determine how DNA functions and which genes are manifested, regardless of the DNA sequence itself. Epigenetics includes a number of molecular processes that significantly affect the activity of the genome without changing the DNA sequence in the genes themselves.
One of the most common processes of this type is DNA methylation, when molecular components called methyl groups (made up of methane) are attached to DNA, which turn genes on and off and regulate gene expression. It has been shown that environmental factors, such as temperature and emotional stress, can alter the course of DNA methylation, and changes can become part of a permanent program and begin to be inherited by subsequent generations. This process is known as epigenetic inheritance.
Another important epigenetic process discovered in recent years is histone modification. Histones are proteins that attach to DNA and change its structure, and DNA, in turn, wraps around histones like beads on a string. The combination of DNA and histones is called chromatin structures, and the coils, loops, and ropes in chromatin are a response to environmental stress that can permanently alter gene expression.
More recently, scientists have documented the process of RNA methylation, in which methyl groups are attached to helper molecules, altering gene expression and protein production in subsequent generations. In addition, the action of so-called non-coding RNAs, small RNA molecules that bind to DNA, RNA and proteins, also alter gene expression regardless of the DNA sequence.
All of these mechanisms of epigenetics are critical and play an important role in the molecular regulation of DNA functions. It follows from this that the norms of biology are never built only on genetic or only on epigenetic processes. On the contrary, the processes of genetics and epigenetics are intertwined. One doesn't work without the other.
According to the laws of epigenetics, for a change to have an impact on evolution, it must be inherited by subsequent generations in the form of DNA sequences or gene mutations. But epigenetic inheritance does not correlate with many of Mendel's laws that apply to classical genetics or neo-Darwinian evolutionary theory. According to these rules, DNA sequences and genes function separately, like particles: during reproduction, "particles" from one parent are randomly combined with a pair from the other parent, which leads to the emergence of a new DNA sequence and a new manifestation of hereditary traits.
In contrast, epigenetic inheritance occurs when the germ line (sperm or egg) transmits epigenetic information from one generation to the next, even in the absence of direct long-term environmental factors. These factors, like environmental stress, are especially strong during embryonic development, for example, during the period when the reproductive organs of the fetus are transformed into testes in males and ovaries in females, in order to produce sperm and eggs at a later age. Indeed, environmental factors at this critical moment can induce permanent epigenetic changes through DNA methylation, histone modifications, and rearrangement of noncoding RNAs.
In 2000, my team at the University of Washington received evidence for this nongenetic form of inheritance, and it is quite convincing. The findings, which my group published in Science in 2005, showed that chemicals in the environment can promote the transmission of certain diseases in three generations of rats and beyond, even without prolonged exposure. Later, that is, in the past ten years, this phenomenon was documented by many laboratories for various species. One example is a report by Graham Burdge and his team at the University of Southampton, UK, on how overfeeding rats caused epigenetic metabolic disorders for three generations to come.
In another work, Sibum Sung and colleagues at the University of Texas at Austin found that drought and temperature fluctuations cause epigenetic evolution of plants, leading to generations of changes in growth and flowering. According to a number of studies, environmental stress can contribute to epigenetic changes that are passed on to subsequent generations and cause pathologies in them. A recent study by Gerlinde Metz and her colleagues at the University of Lethbridge in Canada showed that when pregnant rats were imprisoned or forced to swim, epigenetic damage occurred that threatened newborn babies. This generic stress triggered a chain of epigenetic inheritance of abnormalities over several generations along the line of the stressed female. The role of environmental stress in the epigenetic inheritance of diseases over several generations is now supported by several other studies.
Epigenetic inheritance under the influence of environmental factors is observed in plants, insects, fish, birds, rodents, pigs and humans. Hence, it is a very persistent phenomenon. It was shown that epigenetic transgenerational inheritance of various phenotypic traits and diseases occurs in most organisms in at least ten generations, and the most extensive studies have studied hundreds of plant generations. For example, even Carl Linnaeus in the 18th century noticed that flowering in plants can be caused by an increase in temperature, and later it turned out that this is due to modifications of DNA methylation in the first plant in the chain, and the trait persists for a hundred generations. In worms, the signs caused by changes in nutrition extend over 50 generations. In mammals,each generation of which lives longer, we have discovered deviations from the norm caused by the influence of toxins, spreading to the next ten generations. Most of these studies show that transgenerational traits continue rather than degenerate. Even in Waddington's experiment with flies, it was a question of 16 generations, and all had altered properties that continue to be passed from one generation to another to this day.which continue to be passed from one generation to another to this day.which continue to be passed from one generation to another to this day.
Changes in the environment are literally changing biology, and this is largely in line with Lamarck's assumption. Even if the exposure is short-lived, biological modifications that manifest themselves in certain traits or diseases are transmitted between generations.
The environment plays an essential role in evolution. In a Darwinian sense, it determines which individuals and species will survive in the unforgiving machine of natural selection. But a large number of environmental factors can also influence evolution and biology directly, that is, by means of epigenetics: the properties of the body can change under the influence of temperature or light, or in response to nutritional parameters such as a high-fat diet or calorie restriction. A variety of chemicals and toxins from plants and the environment in general can affect phenotypic changes and health.
One example that we studied in our laboratory involved chemical effects on variability of signs and disease. We examined the ability of the toxin vinclozolin, the most commonly used fungicide in agriculture, to influence traits through epigenetic changes. First, we exposed a pregnant female rat to this fungicide, after which we waited three generations for her offspring, no longer using the toxin. Almost all males showed a decrease in the number and viability of spermatozoa, and with age, cases of infertility. We also observed a number of other disease states in both males and females, three generations separated from direct exposure to the toxin. Among these conditions were abnormalities in the functions of the testicles, ovaries, kidneys, prostate, mammary glands and brain. Corresponding epigenetic changes in spermatozoa entail changes in DNA methylation and expression of noncoding RNAs.
Our study showed that exposure to the toxin vinclozolin led to sexual selection three generations ahead. To observe sexual selection, or mate preference, which has been considered the main driving force of evolution since Darwin presented his theory, females from other litters were given the opportunity to choose between male offspring of the exposed individual and other males. In the overwhelming majority of cases, females chose those who lacked epigenetic transgenerational changes, that is, males whose ancestors were not affected by the toxin. In other words, the influence of the fungicide forever changed the epigenetics of the sperm of the offspring, which, in turn, indicates the hereditary nature of the characteristics of sexual selection, which, as you know,seeks to reduce the spread of genes in a population and directly affects evolution on a microevolutionary scale.
In another recent study, we touched on the macroevolutionary scale of evolution - speciation. One of the classic examples of speciation is Darwin's finches in the Galapagos Islands. A group of finches of the same species produced sixteen new species, which differed in size and had variability in other traits, such as the structure of the beak. Our team decided to explore five different species. We followed DNA sequence mutations from one species to another, but the number of epigenetic changes in DNA methylation (epimutations) was higher and more correlated with the phylogenetic distance between species (pedigree). Although there is currently more emphasis on neo-Darwinian genetic concepts, our findings suggest that epigenetics plays a role in speciation and evolution of Darwin's finches.
The recognition of the role of epigenetics in evolution continues to grow. One interesting study compares Neanderthal and human DNA, and clearly shows that genetic differences are markedly less pronounced than epigenetic ones regarding changes in DNA methylation in genomes. In short, combining neo-Lamarckian and neo-Darwinian concepts into one theory provides a much more efficient molecular basis for evolution.
Evolution is influenced by both neo-Darwinian and neo-Lamarckian mechanisms, and they seem to be closely related. Indeed, since environmental epigenetics can increase the variability of traits within one population, it expands the possibilities of natural selection, in which adaptive traits dominate all others. Classical neo-Darwinian evolution builds on genetic mutation and gene variation as the primary molecular mechanism that creates diversity. To these mechanisms is added the phenomenon of epigenetics, which directly increases the number of variations in traits, which increases the chances of the environment becoming a mediator in the process of evolution and natural selection.
A critical additional consideration for us is the ability of epigenetics to alter the stability of the genome and, thus, directly induce those genetic mutations that are observed in cancer biology. Such genetic mutations include copy number variations (the number of repetitions of a short DNA sequence) and point mutations (changes in individual nucleotides outside the DNA sequence) in subsequent generations. It is known that almost all genetic mutations have epigenetic precursors - changes that increase the degree of susceptibility to mutations. We observed how the direct impact of the environment in the first generation did not cause genetic mutations, but led to epigenetic changes, and in subsequent generations an increase in the number of genetic mutations was found. Since epigenetics is associated with both trait variability,so also with mutations, it accelerates the engine of evolution, which cannot be done by Darwinian mechanisms on their own.
Many are skeptical of a unified theory of evolution, especially in light of the paradigm of genetic determinism, which has influenced biological disciplines for over 100 years. Genetic determinism views DNA as the basic building block of biology, and DNA sequence as the ultimate control at the molecular level.
Probably the magic figure of genetic determinism was the sequencing of the human genome, the purpose of which was to provide conclusive evidence of the primacy of the gene. According to forecasts, genome-wide studies were to identify biological markers of normal and abnormal life phenomena and highlight the prerequisites for diseases. But after the advent of sequencing, the main hypothesis of genetic determinism - the statement that most of human biology and diseases can be interpreted through the prism of genetics - has not been confirmed.
Genetics has been studied by many generations of scientists and the public, but few have turned to the relatively new science of epigenetics: in practice, the inclusion of epigenetics in the study of the molecular elements of biology and evolution has met with opposition. Both Watson, who played a role in the discovery of the structure of DNA, and Francis Collins, whose work in sequencing the DNA genome was significant, initially questioned the importance of the epigenetic factor, but today both are more favorably disposed. Francis Collins is now the head of the US National Institutes of Health. However, it is not surprising that after 100 years of genetic determinism, many are resisting paradigm changes.
A month after I put forward a unified theory of evolution, and it was published in Genome Biology and Evolution in 2015, David Penny of Massey University New Zealand suggested that epigenetics is simply a genetic component about inherited traits. Other recent publications, such as an article by Emma Whitelaw of Australia's La Trobe University, have challenged the concept of Lamarckian epigenetic inheritance in mammals.
Despite opposition, I am convinced that we have reached a point where a paradigm shift is imminent. The recognition that epigenetics played a role in evolution does not disprove the importance of genetics. One who takes neo-Lamarckian ideas into account does not at all challenge classical neo-Darwinian theory. Recognized teachings are important and accurate, but they are pieces of broader, more detailed material that expands our understanding by integrating all of our observations into a coherent whole. The unified theory shows how the environment simultaneously influences phenotypic diversity and simplifies natural selection, as shown in the diagram above.
More and more evolutionary biologists are showing a growing interest in the role of epigenetics, a number of mathematical models have already been created that combine genetics and epigenetics into a single system, and this work has paid off with interest. Looking at epigenetics as a complementary molecular mechanism helps to understand phenomena such as gene drift, genetic assimilation (when a trait developed in response to environmental conditions ends up being encoded in the genes), and even the theory of neutral evolution, according to which most changes occur. not in response to natural selection, but by chance. By introducing an expanded molecular mechanism for observation by biologists, the new models create a deeper, finer and more accurate scenario for overall evolution.
Taken together, this data requires us to rethink the old standard, genetic determinism, in search of gaps. In 1962, Thomas Kuhn suggested that when anomalies arise in the current paradigm, it is necessary to pay attention to new knowledge: this is how the scientific revolution is born.
A unified theory of evolution should combine neo-Darwinian and neo-Lamarckian aspects to broaden our understanding of how the environment affects the evolutionary process. For Darwin's sake, one cannot discount Lamarck's contribution over 200 years ago. On the contrary, it must be taken into account in order to create a more convincing and comprehensive theory. Likewise, genetics and epigenetics cannot be viewed as conflicting areas; on the contrary, they should be combined to obtain a wider range of molecular factors and with their help explain what drives our life.