Advantageous Female Mosaicism: X-Chromosome Inactivation

As I talked last week about epigenetics, I found the example of X-Chromosome Inactivation extremely interesting. So, I resolved to explain more about.

            As we know, one of the female X-Chromosome in each cell is inactivated by methylation (epigenetic process) as a mechanism of dose compensation related to the male quantity of gene expression.  Half of the female’s cells has a working X chromosome from her mother while the other half has active X chromosome from her father. In this way, a cellular mosaicism is result from the X inactivation. The choice of the X-Chromosome to be inactivated is random. In the fetal development each cell chooses which X they will inactivate: the one from the father or the one from the mother.  

          The gene responsible for inactivating one X-Chromosome is called X inactive specific transcript (XIST). This X-linked gene is transcribed in the chromosome that will be inactivated. Its transcription causes methylation and modification of chromosome’s chromatin, which makes the chromosome inactive. (Migeon, 2007)

             The female mosaicism provides to women a biological advantage. This is not difficult to understand: a single X chromosome in males make them vulnerable. Any mutation that affects a gene on their maternal X chromosome will be expressed in 100% of their cells. In contrast, women have two X chromosome in each cell: when there is a mutation in a gene on one of their X chromosomes, they have a normal copy of that gene on another one. Because of X inactivation, the mutation will be expressed in only half the cells (Migeon, 2007). Therefore, X-linked diseases are more severe and lethal in men than in women.

        According to Migeon (2007), in the course of evolution, mammalians began with identical sex chromosomes of reptilian origin. Then, the Y chromosome has been progressively reduced in size and one of its genes became a sex-determining gene. As result of gene’s losses, this chromosome has now less than 100 genes while X-chromosome has about 1100 genes. Thus, mammals inactivate one of the two X chromosomes for dosage compensation. Other organisms also make dose compensation but curiously in a different way. Flies, for example, increase the expression of the single X chromosome in the male to achieve the same production as that from the two X chromosomes in the female.

An example of female mosaicism caused by X-Chromosome Inactivation: A mutation in a gene for sweat glands from one X-Chromosome affects some parts of the body while tissues that express the normal X-Chromosome are not affected.

REFERENCE LIST:

Migeon, B. R. (2007). Why Females Are Mosaics, X-Chromosome Inactivation, and Sex Differences in Disease. Gender Medicine, vol. 4, no. 2. 

Epigenetics

For each tissue or cell groups in multicellular organisms, cells express specific activity and phenotype, different from other tissues’ cells; despite all of them have the same genetic material. This differentiation happens due to epigenetic mechanism: a regulation of genes that controls which genes will be expressed and which will be ignored. Epigenetics enables identical twins, with identical genes, to have different traits and personalities (Williams, 2013).

                Epigenetics is composed by chemical flags and markers on genes that are copied with genes during the DNA replication. It can alter gene expression without altering the DNA sequence by blocking or activating a gene expression. Evidences show that the environment may alter the epigenetic regulation. Also, epigenetic modifications can confer phenotypic plasticity and in some cases heritability to offispring (Arinmondo, 2012).

                DNA methylation is one type of epigenetic regulation. The linking of methyl groups to certain nitrogenous bases impedes the gene expression. Another way to regulates genes is by histone modifications. Histones are proteins whereby DNA is enrolled around to compact (part of chromatin structure). The turning out of histones enables the DNA transcription (activating gene expression). Paola Arinmondo (2012) affirmed that other epigenetic modifications have been discovered and she cited nucleosome positioning and non-coding RNAs.

              Epigenetics is related to certain important phenomena of controlling gene expression. Imprinting and X-chromosome inactivation are among these phenomena. Imprinting occurs when one allele of certain gene is activated while another one is methylated in cases of gene expression by one single allele. X-chromosome inactivation is one interesting mechanism whereby women balance the quantity of gene expression in their genome by methylation of one of their X-chromosomes. As men have little gene expression in their Y-chromosome, women would have excessive gene expression if both their X-chromosomes were active. 

Biologists are interested in epigenetics researches due to the non-evident genetic causes of certain diseases. Abnormal epigenetic patterns are found in many diseases, including cancer. For example, the decrease in methylation could cause excessive or improper expression of genes such as those that express cell growth. Also, epigenetic errors could methylate tumor suppressor genes. According to Arinmondo (2012), there are chemical modifiers that can reverse epigenetic alterations and it could be a promise to therapeutic use. Some studies have focused in developing chromatin modifying agents as anticancer therapy. However, Williams (2013) argues that we do not have appropriate technology to read a person’s epigenome and it has still a long way to go.

REFERENCE LIST

Williams, S. C. P. February 26, 2013, ‘Epigenetics’, Proceedings of the National Academy of Sciences, vol. 110, no. 9, p. 3209.

Arimondo, P. B. November 2012, ‘Epigenetics’, Biochimie, vol. 94, issue 11, pp. 2191-2192

Phenotypic Plasticity

             To study evolutionary process, it is important to consider the effects of the environment on the process of development. Phenotypic plasticity is the capability of genotypes to response to environmental alterations. Thus, they can modify their phenotypic expression with morphological or physiological adjustments. Some responses are unavoidable, for example, the decrease in growth under adverse conditions for the development. According to Scheiner (1993), variances in allelic expression across environments and changes in interactions among loci are likely the causes of plasticity in a genetic level.

             As it can be seen in the figure 1 (Scheiner, 1993), the environment influences evolutionary processes in two ways. Firstly, it determinates the fitness of an individual’s phenotype by natural selection. In the second way, it establishes the phenotype interacting with the developmental process. Thus, the environment may change the phenotypic expression of a genotype (phenotypic plasticity). Additionally, the figure shows three sources of phenotypic variation: the genome, the environment and random accidents of development. These random processes are due to internal events that causes change; it is distinct from the environmental interaction. Therefore, Scheiner supposes that different phenotypes may come from genetically identical individuals grown in identical environments.

               

Figure 1 (Schiner, 1993) 

                It is important to clarify that plasticity is specific to a trait instead of an entire genotype. Some traits may be plastic responding to certain environment, while another may not. There are labile and fixed traits. The labile ones get change as fast as the environment while some traits are fixed during development such as size following metamorphosis in holometabolous insects. (Scheiner, 1993)

                 Scientists try different measures to quantify the phenotypic plasticity. To know if the plasticity of a trait is adaptive, it is measured the relationship between the trait plasticity and fitness averaged across environments. Despite, the study of phenotypic responses across more than two environments may be complex. The interests in these analyses are to compare populations and to predict responses to selection. The probable processes of adaptation to environmental stress resulting from plasticity could provide predictions about species responses to the climate change. Therefore, these studies could be the key to ensure the stability of populations before global changes.  

                Given this information, do you think it is possible to predict species responses to selection? Could we predict the behaviour of populations before global change? What do you think about the importance of plasticity?

REFERENCE LIST

Scheiner, SM 1993, ‘Genetics and evolution of phenotype plasticity’, The Annual Review of Ecology, Evolution, and Systematics, no. 24, pp. 35-68.

An Introduction: Genetics and Evolution

As basic concept of genetics, phenotype is all morphological, physiological and even behavioural characteristics of organisms. According to Weatherall (2009), phenotype is all the observable characteristics. Examples of phenotype are flower color, eye color, blood type and the amino acid sequence of a protein. The genotype is the genetic constitution of the individual, the genes it inherited from its parents. The genotype with an environmental interaction establishes the phenotype.
          One significant question over genetics is, due to complex interactions of thousands of genes between themselves and the environment, how to relate gene organization and function to a phenotype. This is an issue which many researchers are focused on. For the moment, evolutionary biologists know that mutations can alter the structure of genes products, giving a rise to diversity of phenotypes. Each genetic makeup can provide a phenotype with adaptive capabilities to certain individuals and for a given environment at a given time. This means natural selection does not act on genes or genetic characteristics singly, but on individuals with all their genetic load.

Therefore, genetics is a determinant factor in the evolutionary processes. Indeed, heritable fitness variation within a population is a key factor to evolution by natural selection (Zhang, 2010). Although Darwin understanding that a factor of heritage and a source of variability are required in his theory, he did not know those mechanisms.   

Biologists strove to join Darwinian evolution with Mendelian genetics creating the synthetic theory of evolution, or Neo-Darwinism. They concluded that evolution is a gradual process including mutation, selection and drift which is explained by population genetic (Zhang, 2010). In this way, it was discovered that the primary source of variability are mutations and genetic recombination. Mutations introduce genetic newness to genotypes, while genetic recombination by sexual reproduction creates variability due to the arising of multiple different gene combinations.

The greater the diversity, the greater the probability of a population to adapt to changes occurring in this environment. Homogeneous population could be eliminated from their habitat if change occurs. Over time, certain genes and consequently certain characteristics are eventually eliminated from populations to the detriment of others that are implanted, thereby causing evolution.

From these basic concepts and knowledge, I will post here related matters objects of scientific study.

REFERENCE LIST

Zhang, J. (2010) Evolutionary genetics: progress and challenges. In: Evolution Since Darwin: The First 150 Years. M. A. Bell, D. J. Futuyma, W.F. Eanes, J. S. Levinton, eds., Sinauer, Sunderland, Mass. Pp. 87-118

Weatherall, David J(Mar 2009) Genotype–Phenotype Relationships. In: eLS. John Wiley & Sons Ltd, 
Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003403.pub2]