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This article is about the general scientific term. For the scientific journal, see
Genetics (journal).
DNA, the molecular basis for inheritance. Each strand of DNA is a chain of
nucleotides, matching each other in the center to form what look like rungs on a twisted ladder.
Genetics is the science of heredity and variation in living organisms.[1][2] Knowledge of the inheritance of characteristics has been implicitly used since prehistoric times for improving crop plants and animals through selective breeding. However, the modern science of genetics, which seeks to understand the mechanisms of inheritance, only began with the work of Gregor Mendel in the mid-1800s.[3] Although he did not know the physical basis for heredity, Mendel observed that inheritance is fundamentally a discrete process with specific traits that are inherited in an independent manner — these basic units of inheritance are now called genes.
Following the rediscovery of Gregor Johann Mendel's observations in the early 1900s, research in 1910s yielded the first physical understanding of inheritance — that genes are arranged linearly along large cellular structures called chromosomes. By the 1950s it was understood that the core of a chromosome was a long molecule called DNA and genes existed as linear sections within the molecule. A single strand of DNA is a chain of four types of nucleotides; hereditary information is contained within the sequence of these nucleotides. Solved by Watson, Wilkins, and Crick in 1953, DNA's three-dimensional structure is a double-stranded helix, with the nucleotides on each strand physically matched to each other. Each strand acts as a template for synthesis of a new partner strand, providing the physical mechanism for the inheritance of information.
The sequence of nucleotides in DNA is used to produce specific sequences of amino acids, creating proteins — a correspondence known as the "genetic code". This sequence of amino acids in a protein determines how it folds into a three-dimensional structure, this structure is in turn responsible for the protein's function. Proteins are responsible for almost all functional roles in the cell. A change to DNA sequence can change a protein's structure and behavior, and this can have dramatic consequences in the cell and on the organism as a whole.
Although genetics plays a large role in determining the appearance and behavior of organisms, it is the interaction of genetics with the environment an organism experiences that determines the ultimate outcome. For example, while genes play a role in determining a person's height, the nutrition and health that person experiences in childhood also have a large effect.
History of genetics
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Morgan's observation of sex-linked inheritance of a mutation causing white eyes in
Drosophila led him to the hypothesis that genes are located upon chromosomes.
Although the science of genetics has its origins in the work of Gregor Mendel in the mid-1800s, various theories of inheritance preceded Mendel. These theories generally assumed that there existed an inheritance of acquired characteristics (also known as "soft inheritance"): the belief that individuals inherit traits that have been strengthened in their parents. Today, the theory is commonly associated with Jean-Baptiste Lamarck, who used this pattern of inheritance to explain the evolution of various traits within species (these changes are now understood to be the product of natural selection rather than a product of soft inheritance).
Mendelian and classical genetics
The modern science of genetics traces its roots to the observations made by Gregor Johann Mendel, a German-Czech Augustinian monk and scientist who made detailed studies of the nature of inheritance in plants. In his paper "Versuche über Pflanzenhybriden" ("Experiments on Plant Hybridization"), presented in 1865 to the Brunn Natural History Society, Gregor Mendel traced the inheritance patterns of certain traits in pea plants and showed that they could be described mathematically.[4] Although not all features show these patterns of Mendelian inheritance, his work suggested the utility of the application of statistics to the study of inheritance.
The significance of Mendel's observations was not understood until early in the twentieth century, after his death, when his research was re-discovered by other scientists working on similar problems. The word "genetics" itself was coined in 1905 by William Bateson, a significant proponent of Mendel's work, in a letter to Adam Sedgwick.[5] The adjective "genetic" (derived from the Greek word "genno" γεννώ: to give birth) predates the noun, dating back to the 1830's and first used in the biological sense in 1859 by Charles Darwin in the The Origin of Species.[6] Bateson publicly promoted and popularized usage of word "genetics" to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization in London, England, in 1906.[7]
In the decades following rediscovery and popularization of Mendel's work, numerous experiments sought to elucidate the molecular basis of DNA. In 1910 Thomas Hunt Morgan argued that genes reside on chromosomes, based on observations of a sex-linked white eye mutation in fruit flies. In 1913 his student Alfred Sturtevant used the phenomenon of genetic linkage and the associated recombination rates to demonstrate and map the linear arrangement of genes upon the chromosome.
Francis Crick's first sketch of a DNA double helix.
Molecular genetics
Although chromosomes were known to contain genes, chromosomes were composed of both protein and DNA — it was unknown which was critical for heredity or how the process occurred. In 1928, Frederick Griffith published his discovery of the phenomenon of transformation (see Griffith's experiment); sixteen years later, in 1944, Oswald Theodore Avery, Colin McLeod and Maclyn McCarty used this phenomenon to isolate and identify the molecule responsible for transformation as DNA.[8] The Hershey-Chase experiment in 1952 identified DNA (rather than protein) as the genetic material of viruses, further evidence that DNA was the molecule responsible for inheritance.
James D. Watson and Francis Crick resolved the structure of DNA in 1953, using the X-ray crystallography work of Rosalind Franklin that indicated the molecule had a helical structure. Their double-helix model paired a sequence of nucleotides with a "complement" on the other strand. This structure not only provided a physical explanation for information contained within the order of the nucleotides, but also a physical mechanism for duplication through separation of strands and the reconstruction of a partner strand based on the nucleotide pairings. Although the structure explained the process of inheritance, it was still unknown how DNA influenced the behavior of cells. In the following years many scientists sought to understand how DNA controls the process of protein production within ribosomes, eventually discovering the transcription of DNA into messenger RNA and uncovering the genetic code which links the nucleotide sequence of messenger RNA to the amino acid sequence of protein.
With this molecular understanding of DNA, an explosion of research based on this understanding of the molecular nature of DNA became possible. The development of chain-termination DNA sequencing in 1977 enabled the determination of nucleotide sequences on DNA,[9] and the PCR method developed by Kary Banks Mullis in 1983 allowed the isolation and amplification of arbitrary segments of DNA.[10] These and other techniques, through the pooled efforts of the Human Genome Project and parallel private effort by Celera Genomics, culminated in the sequencing of the human genome in 2001.
Features of inheritance
Discrete inheritance and Mendel's laws
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A Punnett square depicting a cross between two pea plants heterozygous for purple (B) and white (b) blossoms.
At its most fundamental level, inheritance in organisms occurs by means of discrete traits, called "genes".[11] This property was first observed by Gregor Mendel, who studied the segregation of heritable traits in pea plants.[4][12] In his experiments studying the trait for flower color, Mendel observed that the flowers of each pea plant were either purple or white — and never an intermediate between the two colors. These different, discrete versions of the same gene are called "alleles".
In the case of pea plants, each organism has two alleles of each gene, and the plants inherit one allele from each parent.[13] Many organisms, including humans, have this pattern of inheritance. Organisms with two copies of the same allele are called "homozygous", while organisms with two different alleles are "heterozygous".
The set of alleles for a given organism is called its genotype, while the visible trait the organism has is called its "phenotype". When organisms are heterozygous, often one allele is called "dominant" as its qualities "dominate" the phenotype of the organism, while the other allele is called "recessive" as its qualities "recede" and are not observed. Dominant alleles are often abbreviated with a capital letter, while recessive alleles are given a lowercase version of the same letter.[14] Some alleles do not have complete dominance and instead have incomplete dominance by expressing an intermediate phenotype, or codominance by expressing both alleles at once.[15]
When parents breed to produce children, their children randomly inherit one of the two alleles from each parent. The outcome of these crosses can be visualized by use of a Punnett square. These observations of discrete inheritance and the segregation of alleles are collectively known as "Mendel's first law" or the "Law of Segregation".
Assortment and interactions of multiple genes
Human height is a complex genetic trait.
Francis Galton's data from 1889 shows the relationship between offsping height as a function of mean parent height. While correlated, the remaining variation in offspring heights indicates environment is also an important factor in this trait.
Organisms have thousands of genes, and in sexually reproducing organisms assortment of these genes are generally independent of each other. This means that the inheritance of an allele for yellow or green pea color is unrelated to the inheritance of alleles for white or purple flowers. This phenomenon, known as "Mendel's second law" or the "Law of independent assortment", means that the alleles of different genes get shuffled between parents to form children with many different combinations. (Some genes do not assort independently, demonstrating genetic linkage, a topic discussed later in this article.)
Often different genes can interact in a way that influences the same trait. In the blue-eyed Mary, for example, there exists a gene with alleles that determine the color of flowers: blue or magenta. Another gene, however, controls whether the flowers have color at all: color or white. When a plant has two copies of this white allele, its flowers are white — regardless of whether the first gene has blue or magenta alleles. This interaction between genes is called "epistasis", with the second gene epistatic to the first.[16]
Many traits are not discrete features (eg. purple or white flowers) but are instead continuous features (eg. human height and skin color). These "complex traits" are the product of interactions of many genes.[17] The influence of these genes is mediated, to varying degrees, by the environment an organism has experienced. The degree to which an organism's genes contribute to a complex trait is called "heritability".[18] Measurement of the heritability of a trait is relative, though — in a more variable environment, the environment has a bigger influence on the total variation of the trait. For example, human height is a complex trait with a heritability of 89% in the United States. In Nigeria, however, where people experience a more variable access to good nutrition and health care, height has a heritability of only 62%.[19]
The molecular basis for inheritance
DNA and chromosomes
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Main articles: DNA and Chromosome
The molecular basis for genes is deoxyribonucleic acid (DNA). DNA is composed of a chain of nucleotides, of which there are four types: adenine (A), cytosine (C), guanine (G), and thymine (T). Genetic information exists in the sequence of these nucleotides, and genes exist as stretches of sequence along the DNA chain.[20] Viruses are the only exception to this rule — sometimes viruses use the very similar molecule RNA instead of DNA as their genetic material.[21] The full set of all hereditary material in an organism is called its "genome".
DNA normally exists as a double-stranded molecule, coiled into the shape of a double-helix. Each nucleotide in DNA preferentially pairs with its partner nucleotide on the opposite strand: A pairs with T, and C pairs with G. Thus, in its two-stranded form, each strand effectively contains all necessary information, redundant with its partner strand. This structure of DNA is the physical basis for inheritance: DNA replication duplicates the genetic information by splitting the strands and using each strand as a template for synthesis of a new partner strand.[22]
Genes are arranged linearly along the long chains of DNA sequence, called chromosomes. In bacteria, each cell has a single circular chromosome, while eukaryotic organisms (which includes plants and animals) have their DNA arranged in multiple linear chromosomes. These DNA strands are often extremely long; the largest human chromosome, for example, is about 247 million base pairs in length.[23] The DNA of a chromosome is associated with structural proteins which organize, compact, and control access to the DNA, forming a material called chromatin; in eukaryotes chromatin is usually composed of nucleosomes, repeating units of DNA wound around a core of histone proteins.[24] The full set of hereditary material in an organism (usually the combined DNA sequences of all chromosomes) is called the "genome".
While haploid organisms have only one copy of each chromosome, most animals and many plants are diploid, containing two copies of each chromosome and thus two copies of every gene.[25] The two alleles for a gene are located on identical loci of sister chromatids, each allele inherited from a different parent.
Walther Flemming's
1882 diagram of eukaryotic cell division. Chromosomes are copied, condensed, and organized. Then, as the cell divides, chromosome copies separate into the daughter cells.
An exception exists in the sex chromosomes, specialized chromosomes many animals have evolved that play a role in determining the sex of the organism.[26] In humans and other mammals the Y chromosome has very few genes and triggers the development of male sexual characteristics, while the X chromosome is similar to the other chromosomes and contains many genes unrelated to sex determination. Females have two copies of the X chromosome, but males have one Y and only one X chromosome — this difference in X chromosome copy numbers leads to the unusual inheritance patterns of sex linked disorders.
Reproduction
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When cells divide, their full genome is copied and each daughter cell inherits one copy. This is a simplest form of reproduction and is the basis for asexual reproduction. Asexual reproduction can also occur in multicellular organisms, always producing children which each inherit a full copy of a single parental genome. When asexual reproduction occurs, the child organisms are "clones" as they contain the same genetic material as the parent.
Eukaryotic organisms often use sexual reproduction to generate children which contain a mixture of genetic material inherited from two different parents. The process of sexual reproduction generally alternates between forms which contain single copies of the genome (haploid) and double copies (diploid).[25] Haploid cells fuse and combine genetic material to create a diploid cell with paired chromosomes. Diploid organisms form haploids by dividing, without replicating their DNA, to create daughter cells that randomly inherit one of each pair of chromosomes. Most animals and many plants are diploid for the majority of their lifespan, with the haploid form reduced to single cell gametes.
Although they do not use the haploid/diploid method of sexual reproduction, bacteria have many methods of acquiring new genetic information. Some bacteria can undergo conjugation, transferring a small circular piece of DNA to another bacterium.[27] Bacteria can also take up raw DNA fragments found in the environment and integrate them into their genome, a phenomenon known as transformation.[28] This processes result in horizontal gene transfer, transmitting fragments of genetic information between organisms that would otherwise be unrelated.
Genetic recombination and linkage
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The diploid nature of chromosomes allows for genes on different chromosomes to assort independently during sexual reproduction, recombining to form new combinations of genes. Genes on the same chromosome would theoretically never recombine, however, were it not for the process of chromosomal crossover. During crossover, chromosomes exchange stretches of DNA, effectively shuffling the gene alleles between the chromosomes to .[29] This process of chromosomal crossover generally occurs during meiosis, a series of cell divisions that creates haploid germ cells which later combine with other germ cells to form child organisms.
The probability of chromosomal crossover occurring between two given points on the chromosome is related to the distance between them. For an arbitrarily long distance, the probability of crossover is high enough that the inheritance of the genes is effectively uncorrelated. For genes that are closer together, however, the lower probability of crossover means that the genes demonstrate genetic linkage — alleles for the two genes tend to be inherited together. The amounts of linkage between a series of genes can be combined to form a linear linkage map that roughly describes the arrangement of the genes along the chromosome.[30]
Gene expression and the creation of phenotype
The genetic code
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Main article: Genetic code
The dynamic structure of hemoglobin is responsible for its ability to transport oxygen within mammalian blood.
Genes generally express their functional effect through the production of proteins, which are complex molecules responsible for most functions in the cell.[31] P
Classical
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