UPSC Biology Molecular basis of Inheritance / विरासत का आणविक आधार Inheritance and Development

 Inheritance and Development

1.           Mutation

• Inheritance is the process by which characters are passed on from parent to progeny; it is the basis of heredity. Variation is the degree by which progeny differ from their parents.
• Mutation is a phenomenon which results in alteration of DNA sequences and consequently results in changes in the genotype and the phenotype of an organism. In addition to recombination, mutation is another phenomenon that leads to variation in DNA.
• One DNA helix runs continuously from one end to the other in each chromatid, in a highly supercoiled form. Therefore loss (deletions) or gain (insertion/duplication) of a segment of DNA, result in alteration in chromosomes. Since genes are known to be located on chromosomes, alteration in chromosomes results in abnormalities or aberrations. Chromosomal aberrations are commonly observed in cancer cells.
• In addition to the above, mutation also arise due to change in a single base pair of DNA. This is known as point mutation. A classical example of such a mutation is sickle cell anemia. Deletions and insertions of base pairs of DNA, causes frame-shift mutations.
• There are many chemical and physical factors that induce mutations.

2.           Genetic Disorders

• Broadly, genetic disorders may be grouped into two categories - Mendelian disorders and Chromosomal disorders. Mendelian disorders are mainly determined by alteration or mutation in the single gene. These disorders are transmitted to the offspring.
• The pattern of inheritance of such Mendelian disorders can be traced in a family by the pedigree analysis. Most common and prevalent Mendelian disorders are Haemophilia, Cystic fibrosis, Sickle-cell anaemia, Colour blindness, Phenylketonuria, Thalassemia, etc.
• It is important to mention here that such Mendelian disorders may be dominant or recessive. By pedigree analysis one can easily understand whether the trait in question is dominant or recessive.
• Similarly, the trait may also be linked to the sex chromosome as in case of haemophilia. It is evident that this X-linked recessive trait shows transmission from carrier female to male progeny.

• Haemophilia
• This sex linked recessive disease, which shows its transmission from unaffected carrier female to some of the male progeny has been widely studied.
• In this disease, a single protein that is a part of the cascade of proteins involved in the clotting of blood is affected. Due to this, in an affected individual a simple cut will result in non-stop bleeding.
• The heterozygous female (carrier) for haemophilia may transmit the disease to sons. The possibility of a female becoming a haemophilic is extremely rare because mother of such a female has to be at least carrier and the father should be haemophilic (unviable in the later stage of life).
• The family pedigree of Queen Victoria shows a number of haemophilic descendents as she was a carrier of the disease.

• Sickle-cell anaemia
• This is an autosome linked recessive trait that can be transmitted from parents to the offspring when both the partners are carrier for the gene (or heterozygous). The defei is caused by the substitution of Glutamic acid (Glu) by Valine (Val) at the sixth position of the beta globin chain of the haemoglobin molecule.

• Phenylketonuria
• This inborn error of metabolism is also inherited as the autosomal recessive trait. The affected individual lacks an enzyme that converts the amino acid phenylalanine into tyrosine.                                
• As a result of this phenylalanine is accumulated and converted into phenylpyruvic acid and other derivatives. Accumulation of these in brain results in mental retardation, These are also excreted through urine because of its poor absorption by kidney.

• Chromosomal disorders
• The chromosomal disorders on the other hand are caused due to absence or excess or abnormal arrangement of one or more chromosomes.
• Failure of segregation of chromatids during cell division cycle results in the gain or loss of a chromosome(s), called aneuploidy. For example. Down's syndrome results in the gain of extra copy of chromosome 21.
• Similarly, Turner's syndrome results due to loss of an X chromosome in human females.
• Failure of cytokinesis after telophase stage of cell division results in an increase in a whole set of chromosomes in an organism and, this phenomenon is known as polyploidy. This condition is often seen in plants.
• The total number of chromosomes in a normal human cell is 46 (23 pairs). Out of these 22 pairs are autosomes and one pair of chromosomes are sex chromosome.
• Sometimes, though rarely, either an additional copy of a chromosome may be included in an individual or an individual may lack one of any one pair of chromosomes. These situations are known as trisomy or monosomy of a chromosome, respectively. Such a situation leads to very serious consequences in the individual.
• Down's syndrome. Turner's syndrome, Klinefelter's syndrome are common examples of chromosomal disorders.

• Down’s Syndrome
• The cause of this genetic disorder is the presence of an additional copy of the chromosome number 21 (trisomy of 21).
• This disorder was first described by Langdon Down (1866).
• The affected individual is short statured with small round head, furrowed tongue and partially open mouth. Palm is broad with characteristic palm crease. Physical, psychomotor and mental development is retarded.

• Klinefelter's Syndrome
• This genetic disorder is also caused due to the presence of an additional copy of X-chromosome resulting into a karyotype of 47, XXY.
• Such an individual has overall masculine development, however, the feminine development (development of breast, i.e., Gynaecomastia) is also expressed. Such individuals are sterile.

• Turner’s Syndrome
• Such a disorder is caused due to the absence of one of the X chromosomes, i.e., 45 with X0, Such females are sterile as ovaries are rudimentary besides other features including lack of other secondary sexual characters.

3.           Molecular Basis of Inheritance

• Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are the two types of nucleic acids found in living systems. DNA acts as the genetic material in most of the organisms, RNA though it also acts as a genetic material in some viruses, mostly functions as a messenger.
• DNA is a long polymer of deoxyribonucleotides. The length of DNA is usually defined as number of nucleotides (or a pair of nucleotide referred to as base pairs) present in it. This also is the characteristic of an organism.
• A nucleotide has three components - a nitrogenous base, a pentose sugar (ribose in case of RNA, and deoxyribose for DNA), and a phosphate group. There are two types of nitrogenous bases - Purines (Adenine and Guanine), and Pyrimidines (Cytosine, Uracil and Thymine). Cytosine is common for both DNA and RNA and Thymine is present in DNA.
• DNA as an acidic substance present in nucleus was first identified by Friedrich Meischer in 1869. He named it as 'Nuclein’.
• In 1953 James Watson and Francis Crick, based on the X-ray diffraction data produced by Maurice Wilkins and Rosalind Franklin, proposed a very simple but famous Double Helix model for the structure of DNA.
• The base pairing confers a very unique property to the polynucleotide chains. They are said to be complementary to each other, and therefore if the sequence of bases in one strand is known then the sequence in other strand can be predicted.

4.           Properties of Genetic Material (DNA versus RNA)

• DNA that acts as genetic material. However, it subsequently became clear that in some viruses, RNA is the genetic material (for example, Tobacco Mosaic viruses, QB bacteriophage, etc.).
• Answer to some of the questions such as, why DNA is the predominant genetic material, whereas RNA performs dynamic functions of messenger and adapter has to be found from the differences between chemical structures of the two nucleic acid molecules.
• A molecule that can act as a genetic material must fulfill the following criteria :
• It should be able to generate its replica (Replication).
• It should chemically and structurally be stable.
• It should provide the scope for slow changes (mutation) that are required for evolution,
• It should be able to express itself in the form of 'Mendelian Characters'.
• If one examines each requirement one by one, because of rule of base pairing and complementarity, both the nucleic acids (DNA and RNA) have the ability to direct their duplications. The other molecules in the living system, such as proteins fail to fulfill first criteria itself.
• The genetic material should be stable enough not to change with different stages of life cycle, age or with change in physiology of the organism.
• Stability as one of the properties of genetic material was very evident in Griffith's 'transforming principle' itself that heat, which killed the bacteria, at least did not destroy some of the properties of genetic material.
• This now can easily be explained in light of the DNA that the two strands being complementary if separated by heating come together, when appropriate conditions are provided. Further, 2 Hydroxyl group present at every nucleotide in RNA is a reactive group and makes RNA labile and easily degradable.                                 
• DNA chemically is less reactive and structurally more stable when compared to RNA. Therefore, among the two nucleic acids, the DNA is a better genetic material.
• In fact, the presence of thymine at the place of uracil also confers additional stability to DNA. (Detailed discussion about this requires understanding of the process of repair in DNA, and you will study these processes in higher classes.)
• Both DNA and RNA are able to mutate. In fact, RNA being unstable, mutate at a faster rate. Consequently, viruses having RNA genome and having shorter life span mutate and evolve faster.
• The above discussion indicate that both RNA and DNA can function as genetic material, but DNA being more stable is preferred for storage of genetic information. For the transmission of genetic information, RNA is better.
• From foregoing discussion, an immediate question becomes evident - which is the first genetic material?
• RNA was the first genetic material. There is now enough evidence to suggest that essential life processes (such as metabolism, translation, splicing, etc.), evolved around RNA. RNA used to act as a genetic material as well as a catalyst (there are some important biochemical reactions in living systems that are catalysed by RNA catalysts and not by protein enzymes).
• RNA being a catalyst was reactive and hence unstable. Therefore, DNA has evolved from RNA with chemical modifications that make it more stable. DNA being double stranded and having complementary strand further resists changes by evolving a process of repair.

5.           Salient Features of Human Genome

The human genome contains \[3164.7\] million nucleotide bases. The average gene consists of \[3000\]bases, but sizes vary greatly, with the largest known human gene being dystrophin at \[2.4\] million bases. The total number of genes is estimated at \[30,000\]-much lower than previous estimates of \[80,000\]to \[1,40,000\]genes.

Almost all (\[99.9\]per cent) nucleotide bases are exactly the same in. all people.

The functions are unknown for over 50 per cent of the discovered genes.

Less than 2 per cent of the genome codes for proteins.

Repeated sequences make up very large portion of the human genome.

Repetitive sequences are stretches of DNA sequences that are repeated many times, sometimes hundred to thousand times. They are thought to have no direct coding functions, but they shed light on chromosome structure, dynamics and evolution.

Chromosome 1 has most genes \[\left( 2,968 \right),\]and the Y has the fewest \[\left( 231 \right).\]

Scientists have identified about 1.4 million locations where singlebase DNA differences (SNPs - single nucleotide polymorphism, pronounced as ‘snips’) occur in humans. This information promises to revolutionise the processes of finding chromosomal locations for disease-associated sequences and tracing human history.

6.           DNA Fingerprinting

• \[99.9\]per cent of base sequence among humans is the same.
• Since DNA from every tissue (such as blood, hair-follicle, skin, bone, saliva, sperm etc.), from an individual show the same degree of polymorphism, they become very useful identification tool in forensic applications. Further, as the polymorphisms are inheritable from parents to children, DNA fingerprinting is the basis of paternity testing, in case of disputes.
• The technique of DNA Fingerprinting was initially developed by Alee Jeffreys.

7.           Origin of Life

• Stellar distances are measured in light years. What we see today is an object whose emitted light started its journey millions of year back and from trillions of kilometres away and reaching our eyes now. However, when we see objects in our immediate surroundings we see them instantly and hence in the present time. Therefore, when we see stars we apparently are peeping into the past.
• The Big Bang theory attempts to explain to us the origin of universe. It talks of a singular huge explosion unimaginable in physical terms. The universe expanded and hence, the temperature came down. Hydrogen and Helium formed sometime later. The gases condensed under gravitation and formed the galaxies of the present day universe. In the solar system of the Milky Way galaxy, earth was supposed to have been formed about 4.5 billion years back. There was no atmosphere on early earth. Water vapour, methane, carbondioxide and ammonia released from molten mass covered the surface.
• The UV rays from the sun brokeup water into Hydrogen and Oxygen and the lighter \[{{H}_{2}}\] escaped. Oxygen combined with ammonia and methane to form water, \[C{{O}_{2}}\] and others. The ozone layer was formed. As it cooled, the water vapor fell as rain, to fill all the depressions and form oceans. Life appeared \[500\]million years after the formation of earth, i.e., almost four billion years back.
• Oparin of Russia and Haldane of England proposed that the first form of life could have come from pre-existing non-living organic molecules (e.g. RNA, protein, etc.) and that formation of life was preceded by chemical evolution, i.e., formation of diverse organic molecules from inorganic constituents. The conditions on earth were - high temperature, volcanic storms, reducing atmosphere containing Methane (\[C{{H}_{4}}\]), Ammonia (\[N{{H}_{3}}\]), etc. In\[1953\], S.L. Miller, an American scientist created similar conditions in a laboratory scale.
• The first non-cellular forms of life could have originated 3 billion years back. They would have been giant molecules (RNA, Protein, Polysaccharides, etc.). These capsules reproduced their molecules perhaps. The first cellular form of life did not possibly originate till about \[2000\]million years ago. These were probably single-cells. All life forms were in water environment only.
• This version of a biogenesis, i.e., the first form of life arose slowly through evolutionary forces from non-living molecules is accepted by majority.

8.           Evidences for Evolution

• Evidence that evolution of life forms has indeed taken place on earth has come from many quarters. Fossils are remains of hard parts of life-forms found in rocks. Rocks form sediments and a cross-section of earth's crust indicates the arrangement of sediments one over the other during the long history of earth.
• Different-aged rock sediments contain fossils of different life-forms who probably died during the formation of the particular sediment. Some of them appear similar to modem organisms.
• They represent extinct organisms (e.g.. Dinosaurs). A study of fossils in different sedimentary layers indicates the geological period in which they existed. The study showed that life-forms varied over time and certain life forms are restricted to certain geological timespans. Hence, new forms of life have arisen at different times in the history of earth. All this is called paleontological evidence.
• Comparative anatomy and morphology shows similarities and differences among organisms of today and those that existed years ago. Such similarities can be interpreted to understand whether common ancestors were shared or not. For example whales, bats, Cheetah and human (all mammals) share similarities in the pattern of bones of forelimbs.
• Though these forelimbs perform different functions in these animals, they have similar anatomical structure,                                
• Similarities in proteins and genes performing a given function among diverse organisms give clues to common ancestry. These biochemical similarities point to the same shared ancestry as structural similarities among diverse organisms.
• Man has bred selected plants and animals for agriculture, horticulture, sport or security. Man has domesticated many wild animals and crops. This intensive breeding programme has created breeds that differ from other breeds (e.g., dogs) but still are of the same group. It is argued that if within hundreds of years, man could create new breeds, could not nature have done the same over millions of years?
• Another interesting observation supporting evolution by natural selection comes from England. In a collection of moths made in 1850s, i.e., before industrialization set in, it was observed that there were more white-winged moths on trees than dark-winged or melanised moths. However, in the collection carried out from the same area, but after industrialization, i.e., in 1920, there were more dark-winged moths in the same area, i.e., the proportion was reversed.
• The explanation put forth for this observation was that 'predators will spot a moth against a contrasting background'. During postindustrialisation period, the tree trunks became dark due to industrial smoke and soots. Under this condition the white-winged moth did not survive due to predators, dark-winged or melanised moth survived. Before industrialisation set in, thick growth of almost white-coloured lichen covered the trees -in that background the white winged moth survived but the dark-coloured moth were picked out by predators.
• They will not grow in areas that are polluted. Hence, moths that were able to camouflage themselves, i.e., hide in the background, survived. This understanding is supported by the fact that in areas where industrialisation did not occur e.g., in rural areas, the count of melanic moths was low. This showed that in a mixed population, those that can better- adapt, survive and increase in population size. Remember that no variant is completely wiped out.
• Similarly, excess use of herbicides, pesticides, etc., has only resulted in selection of resistant varieties in a much lesser time scale. This is also true for microbes against which we employ antibiotics or drugs against eukaryotic organisms/cell. Hence, resistant organisms/cells are appearing in a time scale of months or years and not centuries. These are examples of evolution by anthropogenic action. This also tells us that evolution is not a directed process in the sense of determinism. It is a stochastic process based on chance events in nature and chance mutation in the organisms.

9.           Origin and Evolution of Man

• About 15 mya, primates called Dryopithecus and Ramapithecus were existing. They were hairy and walked like gorillas and chimpanzees. Ramapithecus was more man-like while Dryopithecus was more ape-like. Few fossils of man-like bones have been discovered in Ethiopia and Tanzania. These revealed hominid features leading to the belief that about \[3-4\]mya, man-like primates walked in eastern Africa. They were probably not taller than 4 feet but walked up right.
• Two mya, Australopithecines probably lived in East African grasslands. Evidence shows they hunted with stone weapons but essentially ate fruit. Some of the bones among the bones discovered were different. This creature was called the first human-like being the hominid and was called Homo habilis. The brain capacities were between \[650-800\] cc (Cubic Centimetre). They probably did not eat meat.
• Fossils discovered in Java in 1891 revealed the next stage, i.e., Homo erectus about \[1.5\]mya. Homo erectus had a large brain around 900 cc. Homo erectus probably ate meat.
• The Neanderthal man with a brain size of 1400 cc lived in near east and central Asia between \[1,00,000-40,000\]years back. They used hides to protect their body and buried their dead.
• Homo sapiens arose in Africa and moved across continents and developed into distinct races. During ice age between \[75,000-10,000\]years ago modem Homo sapiens arose. Pre-historic cave art developed about \[18,000\]years ago. Agriculture came around \[10,000\]years back and human settlements started.

10.        Experiment of Mendel

• Mendel used a number of contrasting visible characters of garden peas - round/wrinkled seeds, tall/short plants, white/violet flowers and so on. He took pea plants with different characteristics - a tall plant and a short plant, produced progeny from them, and calculated the percentages of tall or short progeny.
• In the first place, there were no halfway characteristics in this firstgeneration, or \[{{F}_{1}}\] progeny - no 'medium-height’ plants. All plants were tall. This meant that only one of the parental traits was seen, not some mixture of the two. So the next question was, were the tall plants in the \[{{F}_{1}}\] generation exactly the same as the tall plants of the parent generation? Mendelian experiments test this by getting both the parental plants and these \[{{F}_{1}}\] tall plants to reproduce by self-pollination.
• The progeny of the parental plants are, of course, all tall. However, the second-generation, or \[{{F}_{2'}}\], progeny of the \[{{F}_{1}}\] tall plants are not all tall. Instead, one quarter of them are short,
• This indicates that both the tallness and shortness traits were inherited in the \[{{F}_{1}}\] plants, but only the tallness trait was expressed. Thus, two copies of the trait are inherited in each sexually reproducing organism. These two may be identical, or may be different, depending on the parentage.

11.        Sex Determination

• How is the sex of a newbom individual determined? Different species use very different strategies for this. Some rely entirely on environmental cues. Thus, in some animals, the temperature at which fertilized eggs are kept determines whether the animals developing in the eggs will be male or female.
• In other animals, such as snails, individuals can change sex, indicating that sex is not genetically determined. However, in human beings, the sex of the individual is largely genetically determined. In other words, the genes inherited from our parents decide whether we will be boys or girls.
• The explanation lies in the fact that all human chromosomes are not paired. Most human chromosomes have a maternal and a paternal copy, and we have 22 such pairs. But one pair, called the sex chromosomes, is odd in not always being a perfect pair. Women have a perfect pair of sex chromosomes, both called X. But men have a mismatched pair in which one is a normal-sized X while the other is a short one called Y. So women are XX, while men are XY. Now, can we work out what the inheritance pattern of X and Y will be?
• Half the children will be boys and half will be girls. All children will inherit an X chromosome from their mother regardless of whether they are boys or girls. Thus, the sex of the children will be determined by what they inherit from their father. A child who inherits an X chromosome from her father will be a girl, and one who inherits a Y chromosome from him will be a boy.

12.        Important Facts

• We often associate Darwin solely with the theory of evolution. But he was an accomplished naturalist, and one of the studies he conducted was to do with the role of earthworms in soil fertility.
• Ideas of heredity and genetics are so essential for understanding evolution. Even Charles Darwin, who came up with the idea of evolution of species by natural selection in the nineteenth century, could not work out the mechanism. It is ironic that he could have done so if he had seen the significance of the experiments his Austrian contemporary, Gregor Mendel, was doing. But then, Mendel too did not notice Darwin's work as relevant to his.