Gene expression and environment

The growth and the development of an organism not only depend on the internal factors in the body but also depend on external factors such as the environment. We know that genes interact with environmental factors. Environment-gene interaction plays an important role in evolution and variation. Phenotypic changes and development often require environmental factors along with the genetic components and thus involve tight regulatory mechanisms. The genes encode certain products which directly or indirectly depend on certain environmental factors. Also, certain environmental factors induce changes in the DNA sequence. Thus gene-environment interaction plays a very important role in the development of an organism. Sunlight and UV rays sometimes harm the genetic components. On a contrary, some conditions require adequate exposure to sunlight. Thus, it depends on the health condition and the type of the genetic component. Here, the environmental factor involves the sunlight. The genetic component involves the gene sequence getting affected.

Penetrance and expressivity:

Image: Penetrance and Expressivity

Certain individuals show a phenotype which may not necessarily match with its respective genotype. The heterozygous gene mostly expresses similar to the homozygous dominant gene. The frequency with which the homozygous dominant gene or the heterozygous dominant gene expresses itself is known as penetrance. So, penetrance is nothing but the frequency of the gene expression (mostly the dominant one). The presence of epistatic or other genes also contributes to the penetrance. Thus, penetrance not only depends on the genotype but also depends on the environment. A complete penetrance is always 100%. It occurs in three main conditions. The first condition involves the expression of one phenotype by all the homozygous recessives. The second condition involves the expression of the other phenotype by all the homozygous dominants. The third condition involves all alike heterozygotes. For example, the individuals in a population express the phenotype associated with the dominant mutant allele. Such a condition involves 100% penetrance since the expected phenotype gets expressed completely. Example of complete penetrance includes human ABO blood group system.

Now, we clearly get to known the concept of incomplete penetrance from the idea of complete penetrance. The expression of the phenotype associated with the genotype is less than 100%. Hence, the condition is known as incomplete penetrance. The expected phenotypic expression is less than 100%. In some of the cases, many genes altogether show a reduced penetrance. Example of reduced penetrance involves a condition known as Brachydactyly. It is a condition in which the trait follows an autosomal dominant pattern and causes shortened fingers affected by a malformation. Many of the cancer genes or oncogenes also exhibit low to moderate penetrance.

The degree to which a penetrant gene or the genotype expresses the respective phenotype in an individual is known as expressivity. Hence, a phenotype manifestation not only depends on the frequency at which a gene expresses the phenotype but also depends on the degree to which it gets expressed. Expressivity also depends on both the factors such as the genotype and the environment. Osteogenesis imperfecta is a condition involving variation in expressivity. The disease gets characterized by the blueness of the sclerae, bone fragility, and hearing loss. It exhibits 100% penetrance. One more condition involves both incomplete penetrance and variable expressivity. Neurofibromatosis is a condition in which fibrous tumor-like outgrowths manifests on an individual’s skin. This autosomal dominant disease shows 50-80% penetrance and also the variable expressivity. The pigmented areas on the skin are known as café-au-lait spots since they resemble the color of the coffee.

Environmental effects:

Various environmental factors affect the expression of the genotype including the age of onset, sex, temperature, and exposure to chemicals. Many genes show their levels of expression at a particular age. Thus, not all the genes get involved in expression all the time. Pattern baldness in males is a common example of the age of onset. Certain gene expressions exclusively depend on the sex of the individual. For example, pattern baldness is more common in males than in females. Such genes are known as sex-linked genes. Their expression depends on the different complements present on the sex chromosomes, mainly the X and the Y chromosomes. On the other hand, sex-limited trait gets expressed due to the genes present on the autosomes resembling in the expression of the genes present on the sex chromosomes. There is one more concept associated with the sex-influenced trait. These traits also get related to autosomes. However, the levels of expression in both the sexes differ. One example of sex-influenced traits is pattern baldness. The autosomal gene becomes dominant in males and recessive in females. The gene expression depends on sex hormones. The male sex hormone known as testosterone plays an important role in the expression of the genes.

Various biochemical reactions require enzymes for catalyzing the steps and taking the process forward. Certain genes (not all the genes) express or encode for temperature-sensitive enzymes. The fur color in Himalayan rabbits is an example of temperature-dependent gene expression. Certain genotypes lead to the appearance of dark fur in the ears, nose, and paws since the local temperature is low there. Certain chemicals also act as environmental factors affecting the gene expression. For example, phenylketonuria is an autosomal recessive disorder characterized by excessive piling up of the amino acid known as phenylalanine. Changes in the chemical composition of the environment also influence the expression of the genes. For example, the administration of new drugs or exposure to bacteria or viruses produces phenocopies. A phenocopy is a non-hereditary phenotypic modification caused due to environmental changes.

Nature versus nurture:

Examples of nature versus nurture are many. Tall parents mostly have tall children. The same concept is applicable to the short parents and their children. Achondroplasia is a kind of dwarfism affecting the development of the leg bones affecting the height and other factors in an individual. A single genotype shows the ability to express a range of phenotypes depending on the exposure to a range of environmental conditions. It is known as the norm of reaction. Thus, many human behavioral traits depend on gene-environment interactions.

References:
[1] Genetics, 9th Edition, Verma P.S. & Agarwal V.K.

[2] Advanced Genetics, Gurbachan S. Miglani
[3] Thompson & Thompson Genetics in Medicine,  Robert L. Nussbaum
[4] Emery's Elements of Medical Genetics, Peter D Turnpenny, Sian Ellard

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What is a gene?

Introduction to genes:

The basic unit of the hereditary material is known as a gene or a cistron. It is an ordered sequence of nucleotides. These sequences encode polypeptide chain via mRNA molecule. Both DNA and RNA are known as nucleic acids. Genetics is the study of structure, function, and the regulation of genes. Studying genes helps us to know more about proteins, cellular functions, and disorders associated with them. In humans, gene targets help to study mutations and target them through advanced drug discovery and therapeutics. In bacteria, genes are manipulated to obtain the desired product. The genetic engineering or recombinant DNA technology helps to manipulate the genes. The desired gene can be integrated into a vector to obtain the desired product.

Modification of plant genes improves the quality of the crop and improves the yield. The genes play an important role in the growth and reproduction of an organism. Slight gene mutations, if harmful, lead to drastic changes in the cell and cause genetic disorders. Genetics plays an important role in preventing genetic disorders through prenatal testing, cytogenetic and molecular genetic techniques. Genes form the main basis of inheritance. We all have some traits obtained from our ancestors. The genes get passed on from generation to generation. We look similar to our parents, yet appear different. Helpful mutations in the genes lead to genetic diversity and variation. That is why we all look different from each other. The complete set of chromosomal and extrachromosomal genes of an organism is known as the genome. It consists of the complete genetic composition of an organism. 

The gene is a heritable determinant of a trait showing the property of segregation. With this reference, the way genes pass within the family are studied. The genes in a family may or may not have diverged from each other. Gene family involves a set of genes that descend from a common ancestor. Genes express themselves in several generations. They also interact with each other. Several genes can collaborate with each other and give rise to one phenotypic trait. The genes may be present in the cell in a particular dosage. It is important to know the frequency of a gene. The genes are present in a specific place on a chromosome, described as gene loci. Gene mapping through annotation of DNA sequences is possible based on gene loci information. DNA sequence annotation with regulatory element sites, coding regions, non-coding regions, and mutations accelerates the mapping. Sometimes many copies of a gene may be present in a chromosome, known as gene redundancy. Thus genes are vast and diversified.

Image 1: Basic genetic structure

HUGO gene nomenclature

It is a standard for gene nomenclature decided by the Human Genome Organisation (HUGO) committee. It is a meaningful naming of a gene. Names accompany useful symbols. A gene symbol is a unique abbreviation of the name of a gene. It consists of uppercase letters in italics, letters in Latin and numbers in Arabic. A putative gene name is locus based.

Here are the naming guidelines:

1.     The symbols must be unique and prohibited to use elsewhere.

2.     The gene symbols must have Latin letters and Arabic numbers

3.     Punctuation marks are not allowed in gene symbols.

4.     The gene symbols should not contain any references of species.

5.     The nomenclature of genes must evolve with the latest technology rather than follow age-old rules.

Structure of a gene:

A gene includes regions preceding and following the coding and non-coding regions. The preceding region is known as the leader sequence which is at 5’ position. It is the untranslated region. There is a coding region known as Exon. An exonic region specifies for an amino acid sequence. These exons are interrupted by non-coding regions known as introns. The untranslated trailer sequences follow them. The untranslated trailer sequences are at 3’ end. The spliced RNA molecule consists of only exons as the non-coding regions or introns for splicing out. Although DNA is a double-stranded molecule, only one strand encodes for RNA synthesis. The sense strand runs from 5’ to 3’ direction and encodes specific molecules. The gene has an open reading frame which is an indication of sense strand direction. The extremities of the gene consist of regulatory sequences. Plus the gene also consists of promoters, enhancers, silencers and other regions.

Image 2: Gene structure

Gene Expression- The Central Dogma

Expression of the genes involves the conversion of the genes coded information into the structures present and operating the cells. The genes are expressed to initiate the synthesis of the mRNA molecule and translated into a protein. Other examples of RNA include rRNA and tRNA. The tRNA and rRNA genes remain untranslated. The gene expression also involves a phenotypic manifestation by a process known as gene action. Differential gene expression studies involve gene expression at different levels. They express differently under different experimental conditions. The central dogma is a two-step process describing the gene expression. Francis Crick proposed the central dogma after the discovery of nucleic acids. DNA undergoes a process of transcription to synthesize RNA which further undergoes translation to form proteins. Not all genes express proteins. Thus, not all genes are transcribed to get RNA. Originally through central dogma, it was postulated that the genetic information is transferred only from nucleic acid to nucleic acid and from nucleic acid to protein. Thus, the genetic information gets transferred from DNA to DNA, DNA to RNA and from RNA to protein. The genetic information never transfers from protein to nucleic acid. The cis-trans test determines the functionality of genes. It determines whether the independent mutations occur in a single gene or several genes.

Cis-trans Complementation test

It helps to determine whether the two mutant sites are in the same functional unit or a gene. It is an allelism test and determines whether two different recessive mutations on the opposite chromosome of a diploid complement each other. The same two mutations in a diploid or a partial diploid show a wild-type phenotype. Cis mutations exhibit a wild-type phenotype. There is no genetic complementation when the mutations are in trans. The term cistron indicates gene.

The gene characterization is possible with sequence, transcription, and homology if it does not contribute to a phenotype. A gene is a functional and physical unit of heredity. The gene code is said to be a triplet. There are total 64 codons that code for 20 different amino acids. 

References:

[1] What is a gene?- Genetics Home Reference - NIH

[2] Gene – Wikipedia
[3] HUGO Gene Nomenclature Committee

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