Excerpt
Traditionally, genomic research was focused on the investigation of DNA sequence which gives rise to the diversity of phenotypes found in nature. It was undoubted that the information which is given by the genomic sequence is the sole factor which is important for the outcome for each individual organism. But since a few decades, a new concept called epigenetics has arisen and shows that we have to modify our knowledge about genetics. “Epi” derives from Greek meaning “on” or “over” and implies that epigenetic mechanisms act on genes via altering the gene expression and regulation without modifying the actual DNA sequence. In epigenetics, we can find the reason why twins (who have the exact same gene sequence) can alter in their phenotype especially concerning their susceptibility to diseases (Fraga et al. 2005; Wong et al.; 2005). Furthermore, it has the potential to answer the question how phenotypic characteristics can alter between generations without a change in the underlying genetic material.
Lamarck vs. Darwin:
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Fig 1: Lamarck's (a) and Darwin's (b) theory how giraffes evolved a long neck (Raven and Johnson, 2002)
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Fig. 2: Lamarckian and Darwinian modalities of evolution. (Koonin and Wolf; 2009)
Broadly seen, the idea behind epigenetics is not new. It appeared 200 years ago, established by Jean - Baptiste Lamarck (1744-1829). He was a French naturalist and proposed the theory of inheritance of acquired traits, i.e. that evolution occurs when the characteristics from parents, which they have acquired during their lifetime (induced by environmental changes which in turn changed their behaviour), pass on to their offspring. He thought in particular of the use (or disuse) of specific organs (like the giraffe’s neck, see Fig 1) that would lead to its gradual functional improvement (or disappearance). He postulates that these improvements are inheritable and would pass on through generations (so that e.g. the giraffe’s neck becomes longer and longer, Fig 1). He believed that evolution is mainly driven by non-randomly acquired, beneficial phenotypic changes which, he said, are inheritable (in particular, those directly affected by the use of organs). However, his theory was discredited to his time and had been displaced by Darwin’s theory of natural selection in the early 20th century. Darwin (1809 – 1882) ascribed a greater importance to random, undirected changes providing material for natural selection. Both had in common that inheritance of acquired characteristics played an important evolutional role. But Lamarck thought that an organism’s inner need drives evolution, whereas Darwin believed devoutly that natural selection of genetic alterations drives the change in evolution which leads to adaptive characteristics in organisms. Thus, Lamarck’s theory became decried. But by the recent increase of epigenetics’ popularity, his name has come back into modern science. Epigenetics is the field which is now suggesting that epigenetic changes, rather than genomic changes in the DNA, play an adaptive role for each organism by heritable transmission of acquired characteristics; although, it does not support Lamarck’s overall concept. It would be carried too far to say that Lamarck’s concept of elongated giraffe’s necks is true. But it is put that environmental factors, such as temperature, can influence epigenetic marks. If one puts Lamarck’s concept into modern genetics, it would say that “1) environmental factors cause genomic (heritable) changes; 2) the induced changes (mutations) are targeted to a specific gene(s) and 3) the induced changes provide adaptation to the original causative factor” (Koonin and Wolf; 2009). But it has nothing to do with the inner need of the organism as Lamarck supposed. The specific environmental factor must cause an adaptive reaction by a molecular mechanism that triggers the genomic change. And this, in turn, stays in contrast to Darwin, who thought that the environment gives a selective force that could fix the random changes in the genome (see Fig 2).
Epigenetics: Definition and mechanisms:
Nowadays, there are numerous definitions but “precise definitions have remained both controversial and elusive” (Ho and Burggren; 2010). According to Berger et al (2009) ‘’an epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence” These alterations or rather the mechanisms by which epigenetics works are diverse and they are involved in processes like gene regulation, development and even diseases like cancer. So, is it possible that gene expression can be changed by different epigenetic ways, e.g. genes can get silenced typically by methylation of specific nucleotides so that the genes will not get transcribed.
Methylation and demethylation are two of the main types belonging to the epigenetic mechanisms, in which a methyl group is transferred to or removed from a cytosine mostly at CpG-islands which have an important regulative role for gene expression. The methylation mechanism is also important in genomic imprinting, another epigenetic mechanism, by which specific alleles get silenced by differential methyl tagging depending on whether the allele is maternally or paternally inherited (e.g. X-chromosome inactivation). This status is partially maintained by differentially methylated regions within or near imprinted genes. Another epigenetic marker is given by the modification of histones, which includes acetylation, methylation and phosphorylation. This is especially important in transcriptional regulation since it influences gene expression by changing the chromatin structure, thereby impeding or facilitating gene activation. Besides, small non-coding RNAs (including microRNAs) have also been shown to be involved in epigenetic regulation through chromatin/histone modification by directing the cytosine methylation (Costa; 2008). Normally, these modifications are erased during germ cell development and hence, not heritable. But these alterations are stably maintained and thus, inheritable and can have long lasting effects on the gene expression through generations without altering the actual gene sequence (Anway et al.; 2005). In contrast to the genome, the so called “epigenome” is relatively dynamic and is potentially reversible and can be influenced by different environmental factors, especially during the fetal and early postpartal phase. Furthermore, each cell of an organism must not have the same epigenetic alterations: Distinct CpG-islands are differentially methylated in different cell types forming a cell specific methylation pattern. All in all, with the help of these dynamic epigenetic alterations, the genome is able to respond much faster to environmental changes than by changing its actual DNA sequence. Hence, it provides a rapid mechanism to adapt to the environment; e.g. they are able to change the phenotype within one generation in the agouti mice which show a dramatic heritable change in their fur colour (Morgan et al.; 1999).
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Fig. 3: Five coat colours which represent the variety of differentially coloured agouti mice from yellow, over mottled to brown (Dolinoy et al.; 2006).
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