A chromosome is a deoxyribonucleic acid (DNA) molecule with part or all of the genetic material (genome) of an organism. Most eukaryotic chromosomes include packaging proteins which, aided by chaperone proteins, bind to and condense the DNA molecule to prevent it from becoming an unmanageable tangle.[1][2]
Chromosomes are normally visible under a light microscope only when the cell is undergoing the metaphase of cell division (where all chromosomes are aligned in the center of the cell in their condensed form).[3] Before this happens, every chromosome is copied once (S phase), and the copy is joined to the original by a centromere, resulting either in an X-shaped structure (pictured to the right) if the centromere is located in the middle of the chromosome or a two-arm structure if the centromere is located near one of the ends. The original chromosome and the copy are now called sister chromatids. During metaphase the X-shape structure is called a metaphase chromosome. In this highly condensed form chromosomes are easiest to distinguish and study.[4] In animal cells, chromosomes reach their highest compaction level in anaphase during chromosome segregation.[5]
Chromosomal recombination during meiosis and subsequent sexual reproduction play a significant role in genetic diversity. If these structures are manipulated incorrectly, through processes known as chromosomal instability and translocation, the cell may undergo mitotic catastrophe and die. Mutations in the cell can allow it to inappropriately evade apoptosis and lead to the progression of cancer.
Some use the term chromosome in a wider sense, to refer to the individualized portions of chromatin in cells, either visible or not under light microscopy. Others use the concept in a narrower sense, to refer to the individualized portions of chromatin during cell division, visible under light microscopy due to high condensation.
Etymology
The word chromosome (/ˈkroʊməˌsoʊm, -ˌzoʊm/[6][7]) comes from the Greek χρῶμα (chroma, "colour") and σῶμα (soma, "body"), describing their strong staining by particular dyes.[8] The term was coined by von Waldeyer-Hartz,[9] referring to the term chromatin, which was introduced by Walther Flemming.
Some of the early karyological terms have become outdated.[10][11] For example, Chromatin (Flemming 1880) and Chromosom (Waldeyer 1888), both ascribe color to a non-colored state.[12]
History of discovery

The German scientists Schleiden,[4] Virchow and Bütschli were among the first scientists who recognized the structures now familiar as chromosomes.[13]
In a series of experiments beginning in the mid-1880s, Theodor Boveri gave the definitive demonstration that chromosomes are the vectors of heredity; his two principles were the continuity of chromosomes and the individuality of chromosomes. It is the second of these principles that was so original. Wilhelm Roux suggested that each chromosome carries a different genetic load. Boveri was able to test and confirm this hypothesis. Aided by the rediscovery at the start of the 1900s of Gregor Mendel's earlier work, Boveri was able to point out the connection between the rules of inheritance and the behaviour of the chromosomes. Boveri influenced two generations of American cytologists: Edmund Beecher Wilson, Nettie Stevens, Walter Sutton and Theophilus Painter were all influenced by Boveri (Wilson, Stevens, and Painter actually worked with him).[14]
In his famous textbook The Cell in Development and Heredity, Wilson linked together the independent work of Boveri and Sutton (both around 1902) by naming the chromosome theory of inheritance the Boveri–Sutton chromosome theory (the names are sometimes reversed).[15] Ernst Mayr remarks that the theory was hotly contested by some famous geneticists: William Bateson, Wilhelm Johannsen, Richard Goldschmidt and T.H. Morgan, all of a rather dogmatic turn of mind. Eventually, complete proof came from chromosome maps in Morgan's own lab.[16]
The number of human chromosomes was published in 1923 by Theophilus Painter. By inspection through the microscope, he counted 24 pairs, which would mean 48 chromosomes. His error was copied by others and it was not until 1956 that the true number, 46, was determined by Indonesia-born cytogeneticist Joe Hin Tjio.[17]
Prokaryotes
The prokaryotes– bacteria and archaea– typically have a single circular chromosome, but many variations exist.[18] The chromosomes of most bacteria, which some authors prefer to call genophores, can range in size from only 130,000 base pairs in the endosymbiotic bacteria Candidatus Hodgkinia cicadicola[19] and Candidatus Tremblaya princeps,[20] to more than 14,000,000 base pairs in the soil-dwelling bacterium Sorangium cellulosum.[21] Spirochaetes of the genus Borrelia are a notable exception to this arrangement, with bacteria such as Borrelia burgdorferi, the cause of Lyme disease, containing a single linear chromosome.[22]
Structure in sequences
Prokaryotic chromosomes have less sequence-based structure than eukaryotes. Bacteria typically have a one-point (the origin of replication) from which replication starts, whereas some archaea contain multiple replication origins.[23] The genes in prokaryotes are often organized in operons, and do not usually contain introns, unlike eukaryotes.
DNA packaging
Prokaryotes do not possess nuclei. Instead, their DNA is organized into a structure called the nucleoid.[24][25] The nucleoid is a distinct structure and occupies a defined region of the bacterial cell. This structure is, however, dynamic and is maintained and remodeled by the actions of a range of histone-like proteins, which associate with the bacterial chromosome.[26] In archaea, the DNA in chromosomes is even more organized, with the DNA packaged within structures similar to eukaryotic nucleosomes.[27][28]
Certain bacteria also contain plasmids or other extrachromosomal DNA. These are circular structures in the cytoplasm that contain cellular DNA and play a role in horizontal gene transfer.[4] In prokaryotes (see nucleoids) and viruses,[29] the DNA is often densely packed and organized; in the case of archaea, by homology to eukaryotic histones, and in the case of bacteria, by histone-like proteins.
Bacterial chromosomes tend to be tethered to the plasma membrane of the bacteria. In molecular biology application, this allows for its isolation from plasmid DNA by centrifugation of lysed bacteria and pelleting of the membranes (and the attached DNA).
Prokaryotic chromosomes and plasmids are, like eukaryotic DNA, generally supercoiled. The DNA must first be released into its relaxed state for access for transcription, regulation, and replication.
Eukaryotes

Chromosomes in eukaryotes are composed of chromatin fiber. Chromatin fiber is made of nucleosomes (histone octamers with part of a DNA strand attached to and wrapped around it). Chromatin fibers are packaged by proteins into a condensed structure called chromatin. Chromatin contains the vast majority of DNA and a small amount inherited maternally, can be found in the mitochondria. Chromatin is present in most cells, with a few exceptions, for example, red blood cells.
Chromatin allows the very long DNA molecules to fit into the cell nucleus. During cell division chromatin condenses further to form microscopically visible chromosomes. The structure of chromosomes varies through the cell cycle. During cellular division chromosomes are replicated, divided, and passed successfully to their daughter cells so as to ensure the genetic diversity and survival of their progeny. Chromosomes may exist as either duplicated or unduplicated. Unduplicated chromosomes are single double helixes, whereas duplicated chromosomes contain two identical copies (called chromatids or sister chromatids) joined by a centromere.

Eukaryotes (cells with nuclei such as those found in plants, fungi, and animals) possess multiple large linear chromosomes contained in the cell's nucleus. Each chromosome has one centromere, with one or two arms projecting from the centromere, although, under most circumstances, these arms are not visible as such. In addition, most eukaryotes have a small circular mitochondrial genome, and some eukaryotes may have additional small circular or linear cytoplasmic chromosomes.
In the nuclear chromosomes of eukaryotes, the uncondensed DNA exists in a semi-ordered structure, where it is wrapped around histones (structural proteins), forming a composite material called chromatin.
Interphase chromatin
During interphase (the period of the cell cycle where the cell is not dividing), two types of chromatin can be distinguished:
Euchromatin, which consists of DNA that is active, e.g., being expressed as protein.
Heterochromatin, which consists of mostly inactive DNA. It seems to serve structural purposes during the chromosomal stages. Heterochromatin can be further distinguished into two types:
Constitutive heterochromatin, which is never expressed. It is located around the centromere and usually contains repetitive sequences.
Facultative heterochromatin, which is sometimes expressed.
Structure of Eukaryotic chromosome
Each chromosome is made up of two chromatids (chromosomal arms) which are joined to each other at a small constricted region called the centromere (primary constriction). These sister chromatids are conjoined twins the result of DNA replication.
The centromere helps the chromatids  attach to the spindle fibres during cell division, it is also concerned with the anaphase movement of the chromosomes, by which the spindle fibers pull the chromatids to the two opposite poles by their contraction during anaphase.
Besides the primary constriction, in certain chromosomes there is a secondary constriction as well. Because a small portion is pinched off from the chromosomal body; this portion is called a 'satellite' and the chromosome is called an SAT chromosome.
The two chromatids are made up of very thin chromatin fibres which are made up of 40% DNA and 60% histone proteins
Each chromatin fibre consists of one DNA helix coiled around eight histone molecules like a loop; such a complex is called nucleosome and resembles a bead on a string.  These nucleosomes pack tighter, during condensation required to get to metaphase.
The primary constriction cannot take up most stains, so during cell division this region is a gap in staining.
Within the primary constriction there is a clear zone called Centromere.
The centromere with the DNA and histone proteins bound to them form a disc shaped structure called kinetochore.
the chromonemata is a word that means a chromatid in the early stage of condensation.

Metaphase chromatin and division

In the early stages of mitosis or meiosis (cell division), the chromatin double helix become more and more condensed. They cease to function as accessible genetic material (transcription stops) and become a compact transportable form. This compact form makes the individual chromosomes visible, and they form the classic four arm structure, a pair of sister chromatids attached to each other at the centromere. The shorter arms are called p arms (from the French petit, small) and the longer arms are called q arms (q follows p in the Latin alphabet; q-g "grande"; alternatively it is sometimes said q is short for queue meaning tail in French[30]). This is the only natural context in which individual chromosomes are visible with an optical microscope.
Mitotic metaphase chromosomes are best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.[31]
During mitosis, microtubules grow from centrosomes located at opposite ends of the cell and also attach to the centromere at specialized structures called kinetochores, one of which is present on each sister chromatid. A special DNA base sequence in the region of the kinetochores provides, along with special proteins, longer-lasting attachment in this region. The microtubules then pull the chromatids apart toward the centrosomes, so that each daughter cell inherits one set of chromatids. Once the cells have divided, the chromatids are uncoiled and DNA can again be transcribed. In spite of their appearance, chromosomes are structurally highly condensed, which enables these giant DNA structures to be contained within a cell nucleus.
Human chromosomes
Chromosomes in humans can be divided into two types: autosomes (body chromosome(s)) and allosome (sex chromosome(s)). Certain genetic traits are linked to a person's sex and are passed on through the sex chromosomes. The autosomes contain the rest of the genetic hereditary information. All act in the same way during cell division. Human cells have 23 pairs of chromosomes (22 pairs of autosomes and one pair of sex chromosomes), giving a total of 46 per cell. In addition to these, human cells have many hundreds of copies of the mitochondrial genome. Sequencing of the human genome has provided a great deal of information about each of the chromosomes. Below is a table compiling statistics for the chromosomes, based on the Sanger Institute's human genome information in the Vertebrate Genome Annotation (VEGA) database.[32] Number of genes is an estimate, as it is in part based on gene predictions. Total chromosome length is an estimate as well, based on the estimated size of unsequenced heterochromatin regions.

Number in various organisms

In eukaryotes
These tables give the total number of chromosomes (including sex chromosomes) in a cell nucleus. For example, most eukaryotes are diploid, like humans who have 22 different types of autosomes, each present as two homologous pairs, and two sex chromosomes. This gives 46 chromosomes in total. Other organisms have more than two copies of their chromosome types, such as bread wheat, which is hexaploid and has six copies of seven different chromosome types– 42 chromosomes in total.

Normal members of a particular eukaryotic species all have the same number of nuclear chromosomes (see the table). Other eukaryotic chromosomes, i.e., mitochondrial and plasmid-like small chromosomes, are much more variable in number, and there may be thousands of copies per cell.

Asexually reproducing species have one set of chromosomes that are the same in all body cells. However, asexual species can be either haploid or diploid.
Sexually reproducing species have somatic cells (body cells), which are diploid [2n] having two sets of chromosomes (23 pairs in humans with one set of 23 chromosomes from each parent), one set from the mother and one from the father. Gametes, reproductive cells, are haploid [n]: They have one set of chromosomes. Gametes are produced by meiosis of a diploid germ line cell. During meiosis, the matching chromosomes of father and mother can exchange small parts of themselves (crossover), and thus create new chromosomes that are not inherited solely from either parent. When a male and a female gamete merge (fertilization), a new diploid organism is formed.
Some animal and plant species are polyploid [Xn]: They have more than two sets of homologous chromosomes. Plants important in agriculture such as tobacco or wheat are often polyploid, compared to their ancestral species. Wheat has a haploid number of seven chromosomes, still seen in some cultivars as well as the wild progenitors. The more-common pasta and bread wheat types are polyploid, having 28 (tetraploid) and 42 (hexaploid) chromosomes, compared to the 14 (diploid) chromosomes in the wild wheat.[60]
In prokaryotes
Prokaryote species generally have one copy of each major chromosome, but most cells can easily survive with multiple copies.[61] For example, Buchnera, a symbiont of aphids has multiple copies of its chromosome, ranging from 10–400 copies per cell.[62] However, in some large bacteria, such as Epulopiscium fishelsoni up to 100,000 copies of the chromosome can be present.[63] Plasmids and plasmid-like small chromosomes are, as in eukaryotes, highly variable in copy number. The number of plasmids in the cell is almost entirely determined by the rate of division of the plasmid– fast division causes high copy number.
Karyotype

In general, the karyotype is the characteristic chromosome complement of a eukaryote species.[64] The preparation and study of karyotypes is part of cytogenetics.
Although the replication and transcription of DNA is highly standardized in eukaryotes, the same cannot be said for their karyotypes, which are often highly variable. There may be variation between species in chromosome number and in detailed organization.
In some cases, there is significant variation within species. Often there is:
1. variation between the two sexes
2. variation between the germ-line and soma (between gametes and the rest of the body)
3. variation between members of a population, due to balanced genetic polymorphism
4. geographical variation between races
5. mosaics or otherwise abnormal individuals.
Also, variation in karyotype may occur during development from the fertilized egg.
The technique of determining the karyotype is usually called karyotyping. Cells can be locked part-way through division (in metaphase) in vitro (in a reaction vial) with colchicine. These cells are then stained, photographed, and arranged into a karyogram, with the set of chromosomes arranged, autosomes in order of length, and sex chromosomes (here X/Y) at the end.
Like many sexually reproducing species, humans have special gonosomes (sex chromosomes, in contrast to autosomes). These are XX in females and XY in males.
Historical note

Investigation into the human karyotype took many years to settle the most basic question: How many chromosomes does a normal diploid human cell contain? In 1912, Hans von Winiwarter reported 47 chromosomes in spermatogonia and 48 in oogonia, concluding an XX/XO sex determination mechanism.[65] Painter in 1922 was not certain whether the diploid number of man is 46 or 48, at first favouring 46.[66] He revised his opinion later from 46 to 48, and he correctly insisted on humans having an XX/XY system.[67]
New techniques were needed to definitively solve the problem:
Using cells in culture
Arresting mitosis in metaphase by a solution of colchicine
Pretreating cells in a hypotonic solution 0.075 M KCl, which swells them and spreads the chromosomes
Squashing the preparation on the slide forcing the chromosomes into a single plane
Cutting up a photomicrograph and arranging the result into an indisputable karyogram.
It took until 1954 before the human diploid number was confirmed as 46.[68][69] Considering the techniques of Winiwarter and Painter, their results were quite remarkable.[70] Chimpanzees, the closest living relatives to modern humans, have 48 chromosomes as do the other great apes: in humans two chromosomes fused to form chromosome 2.
Aberrations

Chromosomal aberrations are disruptions in the normal chromosomal content of a cell and are a major cause of genetic conditions in humans, such as Down syndrome, although most aberrations have little to no effect. Some chromosome abnormalities do not cause disease in carriers, such as translocations, or chromosomal inversions, although they may lead to a higher chance of bearing a child with a chromosome disorder. Abnormal numbers of chromosomes or chromosome sets, called aneuploidy, may be lethal or may give rise to genetic disorders.[71] Genetic counseling is offered for families that may carry a chromosome rearrangement.
The gain or loss of DNA from chromosomes can lead to a variety of genetic disorders. Human examples include:
Cri du chat, which is caused by the deletion of part of the short arm of chromosome 5. "Cri du chat" means "cry of the cat" in French; the condition was so-named because affected babies make high-pitched cries that sound like those of a cat. Affected individuals have wide-set eyes, a small head and jaw, moderate to severe mental health problems, and are very short.
Down syndrome, the most common trisomy, usually caused by an extra copy of chromosome 21 (trisomy 21). Characteristics include decreased muscle tone, stockier build, asymmetrical skull, slanting eyes and mild to moderate developmental disability.[72]
Edwards syndrome, or trisomy-18, the second most common trisomy.[73] Symptoms include motor retardation, developmental disability and numerous congenital anomalies causing serious health problems. Ninety percent of those affected die in infancy. They have characteristic clenched hands and overlapping fingers.
Isodicentric 15, also called idic(15), partial tetrasomy 15q, or inverted duplication 15 (inv dup 15).
Jacobsen syndrome, which is very rare. It is also called the terminal 11q deletion disorder.[74] Those affected have normal intelligence or mild developmental disability, with poor expressive language skills. Most have a bleeding disorder called Paris-Trousseau syndrome.
Klinefelter syndrome (XXY). Men with Klinefelter syndrome are usually sterile and tend to be taller and have longer arms and legs than their peers. Boys with the syndrome are often shy and quiet and have a higher incidence of speech delay and dyslexia. Without testosterone treatment, some may develop gynecomastia during puberty.
Patau Syndrome, also called D-Syndrome or trisomy-13. Symptoms are somewhat similar to those of trisomy-18, without the characteristic folded hand.
Small supernumerary marker chromosome. This means there is an extra, abnormal chromosome. Features depend on the origin of the extra genetic material. Cat-eye syndrome and isodicentric chromosome 15 syndrome (or Idic15) are both caused by a supernumerary marker chromosome, as is Pallister–Killian syndrome.
Triple-X syndrome (XXX). XXX girls tend to be tall and thin and have a higher incidence of dyslexia.
Turner syndrome (X instead of XX or XY). In Turner syndrome, female sexual characteristics are present but underdeveloped. Females with Turner syndrome often have a short stature, low hairline, abnormal eye features and bone development and a "caved-in" appearance to the chest.
Wolf–Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4. It is characterized by growth retardation, delayed motor skills development, "Greek Helmet" facial features, and mild to profound mental health problems.
XYY syndrome. XYY boys are usually taller than their siblings. Like XXY boys and XXX girls, they are more likely to have learning difficulties.
Sperm aneuploidy
Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of aneuploid spermatozoa.[75]  In particular, risk of aneuploidy is increased by tobacco smoking,[76][77] and occupational exposure to benzene,[78] insecticides,[79][80]  and perfluorinated compounds.[81]  Increased aneuploidy is often associated with increased DNA damage in spermatozoa.
See also
Aneuploidy
Chromosome segregation
DNA
Genetic deletion
For information about chromosomes in genetic algorithms, see chromosome (genetic algorithm)
Genetic genealogy
Genealogical DNA test
Lampbrush chromosome
List of number of chromosomes of various organisms
Locus (explains gene location nomenclature)
Maternal influence on sex determination
Non-disjunction
Sex-determination system
XY sex-determination system
X-chromosome
X-inactivation
Y-chromosome
Y-chromosomal Aaron
Y-chromosomal Adam
Polytene chromosome
Neochromosome
Parasitic chromosome
Notes and references

 from HOPES: Huntington's Outreach Project for Education at Stanford

, from the University of Utah's Genetic Science Learning Center
, from the University of Utah's Genetic Science Learning Center

, European network for Rare Chromosome Disorders on the Internet
, Ensembl project, presenting chromosomes, their genes and syntenic loci graphically via the web

 from the U.S. National Library of Medicine
 and comparison to other species
 Support for people with rare chromosome disorders


Mycoplasma laboratorium is a designed, partially synthetic species of bacterium derived from the genome of Mycoplasma genitalium. This effort in synthetic biology is being undertaken at the J. Craig Venter Institute by a team of approximately 20 scientists headed by Nobel laureate Hamilton Smith and including DNA researcher Craig Venter and microbiologist Clyde A. Hutchison III.  Mycoplasma genitalium was chosen as it was the species with the smallest number of genes known at that time.
On May 21, 2010, Science reported that the Venter group had successfully synthesized the genome of the bacterium Mycoplasma mycoides from a computer record and transplanted it into an existing cell of Mycoplasma capricolum that had its DNA removed. The team used M. mycoides instead of M. genitalium because it grew faster. The new bacterium was viable—that is, capable of replicating billions of times—but not, strictly speaking, a truly synthetic life form.[b 1]
It is estimated that the synthetic genome cost US$40 million and 200 man-years to produce.[b 2] Despite the controversy, Venter's company Synthetic Genomics has secured over $110 million in investment capital and inked a $300 million deal with Exxon Mobil to design algae for diesel fuel.[b 3]
Mycoplasma

Mycoplasma genitalium was chosen as it was the species with the smallest number of genes known at that time.
Mycoplasma is a genus of bacteria of the class Mollicutes in the division Tenericutes, characterised by the lack of a cell wall (making it Gram negative) due to its parasitic or commensal lifestyle.
In molecular biology, the genus has received much attention, both for being a notoriously difficult-to-eradicate (immune to beta-lactam and other antibiotics) contaminant in mammalian cell cultures,[a 1] and for its potential uses as a model organism: the second published complete bacterial genome sequence was that of Mycoplasma genitalium, which has one of the smallest genomes of any free-living (non-parasitic) organism.[a 2] The M. pneumoniae genome sequence was published soon afterward and was the first genome sequence determined by primer walking of a cosmid library instead of the whole-genome shotgun method.[a 3] Consequently, this species was chosen as a model for the minimal cell project,[a 4] catalog the entire protein content of a cell.[a 5]
Other genera
Pelagibacter ubique (an α-proteobacterium of the order Rickettsiales) has the smallest known genome (1,308,759 base pairs) of any free living organism and is one of the smallest self-replicating cells known. It is possibly the most numerous bacterium in the world (perhaps 1028 individual cells) and, along with other members of the SAR11 clade, are estimated to make up between a quarter and a half of all bacterial or archaeal cells in the ocean.[a 6] However, this species was identified only in 2002 by rRNA sequences and was fully sequenced in 2005,[a 7] being an extremely hard to cultivate species which does not reach a high growth density,[a 8][a 9]
Additionally, several newly discovered species have fewer genes than M. genitalium, but many essential genes that are missing in Hodgkinia cicadicola, Sulcia muelleri,  Baumannia cicadellinicola (symbionts of cicadas) and Carsonella ruddi (symbiote of hackberry petiole gall psyllid, Pachypsylla venusta[a 10]) may be encoded in the host nucleus as these endosymbionts are acquiring an organelle-like status in a similar way to mitochondria and chloroplasts.[a 11]

Minimal genome project
The team started with the bacterium M. genitalium, an obligate intracellular parasite whose genome consists of 482 genes comprising 582,970 base pairs, arranged on one circular chromosome (the smallest genome of any known natural organism that can be grown in free culture). They then systematically removed genes to find a minimal set of 382 genes that can sustain life.[a 12] This effort was also known as the Minimal Genome Project.
The team intends to synthesize chromosome DNA sequences consisting of these 382 genes. Once a version of the minimal 382-gene chromosome has been synthesized, it is intended to be transplanted into a M. genitalium cell to create Mycoplasma laboratorium.
The resulting Mycoplasma laboratorium bacterium is expected to be able to replicate itself with its man-made DNA, making it the most synthetic organism to date, although the molecular machinery and chemical environment that would allow it to replicate would not be synthetic.[b 4]
In December 2003, the team had reported a fast method of synthesizing a genome from scratch, producing the 5386-base genome of the bacteriophage Phi X 174 in about two weeks.[a 13] However, the genome of Mycoplasma laboratorium is about 50 times larger. In January 2008, the team reported to have synthesized the complete 582,970 base pair chromosome of M. genitalium, with small modifications so that it won't be infectious and can be distinguished from the wild type. They named this genome Mycoplasma genitalium JCVI-1.0.[a 14][b 5] The team had also demonstrated the process of transplanting a (non-synthetic) genome from one Mycoplasma species to another in June 2007.[b 6] In May 2010 they showed that they were able to synthesize the 1,078,809 base pair genome[a 15] of Mycoplasma mycoides from scratch and transplant it into a Mycoplasma capricolum cell; the new genome then took over the cell and the new organism multiplied.[b 7] The new organism was nicknamed Synthia.
Venter hopes to eventually synthesize bacteria to manufacture hydrogen and biofuels, and also to absorb carbon dioxide and other greenhouse gases. George M. Church, another pioneer in synthetic biology, holds that E. coli is a more efficient organism than M. genitalium and that creating a fully synthetic genome is not necessary and too costly for such tasks; he points out that synthetic genes have already been incorporated into E.coli to perform some of the above tasks.[b 5]

On June 28, 2007, a team at the J. Craig Venter Institute published an article in Science Express, saying that they had successfully transplanted the natural DNA from a Mycoplasma mycoides bacterium into a Mycoplasma capricolum cell, creating a bacterium which behaved like a M. mycoides.[a 16]
On Oct 6, 2007, Craig Venter announced in an interview with UK's The Guardian newspaper that the same team had synthesized a modified version of the single chromosome of Mycoplasma genitalium chemically. The chromosome was modified to eliminate all genes which tests in live bacteria had shown to be unnecessary. The next planned step in this minimal genome project is to transplant the synthesized minimal genome into a bacterial cell with its old DNA removed; the resulting bacterium will be called Mycoplasma laboratorium. The next day the Canadian bioethics group, ETC Group issued a statement through their representative, Pat Mooney, saying Venter's "creation" was "a chassis on which you could build almost anything". The synthesized genome had not yet been transplanted into a working cell.[b 4]
On May 21, 2010, Science reported that the Venter group had successfully synthesized the genome of the bacterium Mycoplasma mycoides from a computer record, and transplanted the synthesized genome into the existing cell of a Mycoplasma capricolum bacterium that had had its DNA removed. The "synthetic" bacterium was viable, i.e. capable of replicating billions of times. The team had originally planned to use the M. genitalium bacterium they had previously been working with, but switched to M. mycoides because the latter bacterium grows much faster, which translated into quicker experiments.[b 2] They have also shown that the natural genome of M. mycoides can be transplanted but has yet to show that the same could be done for M. genitalium.[b 8] Venter describes it as "the first species.... to have its parents be a computer".[b 9] The transformed bacterium is dubbed "Synthia" by ETC.  A Venter spokesperson has declined to confirm any breakthrough at the time of this writing, likely because similar genetic introduction techniques such as transfection, transformation, transduction and protofection have been a standard research practice for many years.
Now that the technique has been proven to work with the M. mycoides genome, the next project is presumably to go back to the minimized M. genitalium and transplant it into a cell to create the previously mentioned Mycoplasma laboratorium.
The creation of a new synthetic bacterium was announced in Science on March 25, 2016.  It has only 473 genes, the fewest genes of any freely living organism.
This fast growing new cell, called Syn 3.0, was created by transplanting the genome of Mycoplasma mycoides, with all the unessential DNA removed, into a Mycoplasma capricolum, which had been emptied of its own DNA.
M. genitalium was not used because it reproduces too slowly.
Bacterial genome transplantation
In order to propagate a synthetic genome, the technique to transplant an intact whole bacterial genome into another had to be developed.
Oswald Avery's pioneering experiments in the 1940s showed that some bacteria could take up naked DNA,[a 17] and with the advent of molecular cloning techniques DNA elements could be transformed into competent cells, typically cloning vectors, around 5-20 kbp long,  and even bacterial artificial chromosomes can be maintained.
In 2007, Venter's team reported that they had managed to transfer the chromosome of the species Mycoplasma mycoides to Mycoplasma capricolum by means of:
isolating the genome of M. mycoides: gentle lysis of cells trapped in agar—molten agar mixed with cells and left to form a gel—followed by pulse field gel electrophoresis and the band of the correct size (circular 1.25Mbp) being isolated;
making the recipient cells of M. capricolum competent: growth in rich media followed starvation in poor media where the nucleotide starvation results in inhibition of DNA replication and change of morphology; and
polyethylene glycol-mediated transformation of the circular chromosome to the DNA-free cells followed by selection.[a 16]
The term transformation is used to refer to insertion of a vector into a bacterial cell (by electroporation or heatshock). Here, transplantation is used akin to nuclear transplantation.
The switch from M. genitalium to M. mycoides was spurred due to the faster growth of the latter.[b 2]
Bacterial chromosome synthesis
It is possible to create DNA sequences with the use of chemicals (oligonucleotide synthesis) which is achieved by successive rounds of deprotection and coupling of protected phosphoramidite nucleotides with geometrically decreasing yields to length, making sequences longer than 1000 base-pairs unfeasible. For longer sequences, DNA ligation is required. In 2008 Venter's group published a paper showing that they had managed to create a synthetic genome (a copy of M. mycoides sequence ) by means of a hierarchical strategy:[a 14]
Synthesis → 1kbp: The genome sequence was synthesized by  in 1078 1080bp cassettes with 80bp overlap and NotI restriction sites (inefficient but rare cutter).
Ligation → 10kbp: 109 Groups of a series of 10 consecutive cassettes were ligated and cloned in E.coli on a plasmid and the correct permutation checked by sequencing, this would follow a geometric distribution with expected number of trials of 10.
Multiplex PCR → 100kbp: 11 Groups of a series of 10 consecutive 10kbp assemblies (grown in yeast) were joined by multiplex PCR, using a primer pair for each 10kbp assembly.
Isolation and recombination → secondary assemblies were isolated by means of the plug method above and joining and transformed into yeast spheroplasts without a vector sequence (present in assembly 811-900).
Synthetic genome
In 2010, using the  methods described above, Venter and colleagues created a strain of Mycoplasma mycoides called JCVI-syn1.0 with a synthetic genome.[a 18] Initially the synthetic construct did not work, so to pinpoint the error—which caused a delay of 3 months in the whole project[b 2]—a series of semi-synthetic constructs were created. Given the fact that the natural genome worked, the cause of the failed growth was an frameshift mutation in DnaA, a replication initiation factor, which, once corrected, worked and was verified.[a 18]
The construction of a cell with a synthetic genome was done to test the methodology—allowing more modified genomes to be created in the future. To minimize sources of failure, the genome was created using a natural genome as a template. Due to the large size of a genome, apart from the elements required for propagation in yeast and residues from restriction sites, several differences are present in Mycoplasma mycoides JCVI-syn1.0 notably an E.coli transposon IS1 (an infection from the 10kb stage) and an 85bp duplication.[a 18]
However, the project has received heavy criticism as it claims to have created a synthetic organism. This claim arises from the fact that the genome was synthesized chemically in many pieces (a synthetic method), joined together by means of molecular biological techniques (an artificial method), and transplanted into the cytoplasm of a natural cell (after a few generations, though, the original protein content is undetectable).
The two species used as donor and recipient are of the same genus as the more distant two species are, the less the correct protein interactions are maintained, such as binding factors and binding sites, which mutate together (epistasis).[a 19] Consequently, Paul Keim (a molecular geneticist at Northern Arizona University in Flagstaff) notes that "there are great challenges ahead before genetic engineers can mix match, and fully design an organism's genome from scratch" [b 2] due to this issue.
DNA is the template for protein construction and requires proteins as helper molecules to do so, a chicken-and-egg conundrum solved by the RNA world hypothesis, consequently synthetic naked DNA would require several proteins to create a viable cell. In 2000 and 2002 teams synthesized replicating hepatitis C virus (about 9600 nucleotides long)[a 20] and poliovirus (about 7500 nucleotides long),[a 21]  Viruses, however, replicate by utilising host protein expression machinery. Furthermore, whereas DNA can easily be replicated (using DNA polymerase), transcribed (using RNA polymerase), and translated (using ribosomes and many other factors)—all in vitro, such reactions, so far, use cell extracts and most components have not been synthesized de novo—that is from inorganic or synthetically made organic chemicals only.
Watermarks

A much publicised feature of the Mycoplasma laboratorium is the presence of watermark sequences as an ultimate proof of the achievement and as a publicity stunt—similar to the tradition of chip art, inscriptions on unused portions of microchips visible only by electron microscopy. The 4 watermarks (present in figure 1 in supplementary material of [a 18]) are coded messages in the form of DNA base pairs, of 1246, 1081, 1109 and 1222 base pairs respectively, in natural peptides the 4 nucleotides encode in sets of 3 the 20 natural amino acids by means of the standard genetic code. Each amino acid by convention is represented by a letter, but in nature there is nothing which ties alanine, a molecule, to the Latin letter A, a vowel, so this convention was disregarded in the latter watermarks. In the minimal genome organism the watermark were encoded as amino acids, with V as U, both in reference to Latin inscriptions and the lack of a standard amino acid for U containing the names of the researchers:
(VENTERINSTITVTE, CRAIGVENTER,  HAMSMITH,  CINDIANDCLYDE,  GLASSANDCLYDE).  In the synthetic organism, instead the Latin alphabet—which in English has 26 letters, which is covered only in base 4 with 3 or more digits—was encoded by an undisclosed encoding. The encoding is fixed and 3 digits make an uppercase letter or Ascii symbol, possibly randomly allocated (not Ascii table, frequency or keyboard order).[b 10] The content of the watermarks is as follows:
watermark 1 an Html script which reads to a browser as  text congratulating the decoder with an email link to click to prove the decoding.
watermark 2 contains a list of authors and a quote from James Joyce: "To live, to err, to fall, to triumph, to recreate life out of life".
watermark 3 contains more authors and a quote from Robert Oppenheimer (uncredited): "See things not as they are, but as they might be".
watermark 4 contains yet more authors and a quote from Richard Feynman: "What I cannot build, I cannot understand".
Concerns and controversy
Press coverage
The main controversy from the project is the undue amount of publicity it received from the press due to Venter's showmanship, to the degree that Jay Keasling, a pioneering synthetic biologist and founder of Amyris says "The only regulation we need is of my colleague's mouth".[b 3]
Utility
Despite the funding for practical applications, as stressed by George M. Church, one of the main players in the field of synthetic biology, a few changes are required to obtain useful organisms now, such as biofuel production or bioremediation.[b 3] However, speculation about the distant future's possible applications is rife.
Venter himself is prone to such speculations, having asked for example, "What if we can make algae taste like beef?"[b 3] If it were possible to create  a synthetic cell without the use of preexisting recipient cells, however, many applications would become achievable which would be otherwise unattainable, such as a completely overhauled bacterium that works in a logically controlled way—removing what has been described as 'evolutionary messiness'[a 22]—with lower mutation rates, categorical gene arrangement (colinearity), the possibility of adding novel nucleotides to increase encoding (a feat achieved in vitro (PCR)); or with a completely novel genetic code, such as has been achieved by experiments in which a few additional non-canonical amino acids were added.
Intellectual property
The J. Craig Venter Institute filed patents for the Mycoplasma laboratorium genome (the "minimal bacterial genome") in the U.S. and internationally in 2006.[b 11][b 12][a 23]  This extension of the domain of biological patents is being challenged by the watchdog organization Action Group on Erosion, Technology and Concentration.[b 13]
JCVI-syn3.0

In 2016, the Venter Institute used genes from JCVI-syn1.0 to synthesize an even smaller genome they call JCVI-syn3.0, that contains 531,560 base pairs and 473 genes.[2] Originally in 1996, after comparing M. genitalium with another small bacterium Haemophilus influenza, Arcady Mushegian and Eugene Koonin had proposed that there might be a common set of 256 genes which could be a minimal set of genes needed for viability.[3][4] In this new organism, the number of genes can only be pared down to 473, 149 of which whose functions are completely unknown.[3] The organism with the smallest known set of genes is Nasuia deltocephalinicola, which is an obligate symbiont that cannot survive outside its host, has only 137 genes with a genome size of 112 kb,[5][6] but the minimal genome for any free-living organism would be different depending on its environment.[3]
Similar projects
From 2002 to 2010, a team at the Hungarian Academy of Science created a strain of Escherichia coli called MDS42, which is now sold by Scarab Genomics of Madison, WI under the name of "Clean Genome. E.coli",[b 14] where 15% of the genome of the parental strain (E. coli K-12 MG1655) were removed to aid in molecular biology efficiency, removing IS elements, pseudogenes and phages, resulting in better maintenance of plasmid-encoded toxic genes, which are often inactivated by transposons.[a 24][a 25][a 26] Biochemistry and replication machinery were not altered.

Primary sources

Popular press


Scrooge McDuck is a fictional character created in 1947 by Carl Barks as a work-for-hire for The Walt Disney Company. Scrooge is an elderly Scottish anthropomorphic Pekin duck with a yellow-orange bill, legs, and feet. He typically wears a red or blue frock coat, top hat, pince-nez glasses, and spats. He is portrayed in animations as speaking with a Scottish accent.
Named after Ebenezer Scrooge from the 1843 novel A Christmas Carol, Scrooge is an incredibly wealthy business magnate and self-proclaimed "adventure-capitalist" whose dominant character trait is his thrift. He is brother to Matilda McDuck and Hortense McDuck, the maternal uncle of Della and Donald Duck, the grand-uncle of Huey, Dewey, and Louie, and a usual financial backer of Gyro Gearloose. Within the context of the fictional Duck universe, he is the world's richest person.[5] He is an oil tycoon, businessman, owner of the largest mining concerns, many factories to operate different activities. His "Money Bin"—and indeed Scrooge himself—are often used as a humorous metonyms for great wealth in popular culture around the world.
McDuck was initially characterized as a greedy miser and antihero (as Charles Dickens' original Scrooge was), but in later appearances he has often been portrayed as a charitable and thrifty hero, adventurer and explorer. He was originally created by Barks as an antagonist for Donald Duck, first appearing in the 1947 Four Color story Christmas on Bear Mountain (#178). However, McDuck's popularity grew so large that he became a major figure of the Duck universe. In 1952 he was given his own comic book series, called Uncle Scrooge, which still runs today.
Scrooge was most famously drawn by his creator Carl Barks, and later by Don Rosa. Like other Disney franchise characters, Scrooge McDuck's international popularity has resulted in literature that is often translated into other languages. Comics have remained Scrooge's primary medium, although he has also appeared in animated cartoons, most extensively in the television series DuckTales (1987–1990) and its reboot as the main protagonist of both series.
Comics history
First appearance

Scrooge McDuck, maternal uncle of previously established character Donald Duck, made his first named appearance in the story Christmas on Bear Mountain which was published in Dell's Four Color Comics #178, December 1947, written and drawn by artist Carl Barks. His appearance may have been based on a similar-looking, Scottish "thrifty saver" Donald Duck character from the 1943 propaganda short The Spirit of '43.[6]
In Christmas on Bear Mountain,[7] Scrooge was a bearded, bespectacled, reasonably wealthy old duck, visibly leaning on his cane, and living in isolation in a "huge mansion".[8] Scrooge's misanthropic thoughts in this first story are quite pronounced: "Here I sit in this big lonely dump, waiting for Christmas to pass! Bah! That silly season when everybody loves everybody else! A curse on it! Me—I'm different! Everybody hates me, and I hate everybody!"[8]
Barks later reflected, "Scrooge in 'Christmas on Bear Mountain' was only my first idea of a rich, old uncle. I had made him too old and too weak. I discovered later on that I had to make him more active. I could not make an old guy like that do the things I wanted him to do."[9]
Recurring character
Barks would later claim that he originally only intended to use Scrooge as a one-shot character, but then decided Scrooge (and his fortune) could prove useful for motivating further stories. Barks continued to experiment with Scrooge's appearance and personality over the next four years.
Scrooge's second appearance, in The Old Castle's Secret[10] (first published in June 1948), had Scrooge recruiting his nephews to search for a family treasure hidden in Dismal Downs, the McDuck family's ancestral castle, built in the middle of Rannoch Moor in Scotland. Foxy Relations (first published in November 1948) was the first story where Scrooge is called by his title and catchphrase "The Richest Duck in the World".

First hints of Scrooge's past
The story, Voodoo Hoodoo, first published in Dell's Four Color Comics #238, August 1949, was the first story to hint at Scrooge's past with the introduction of two figures from it. The first was Foola Zoola, an old African sorcerer and chief of the Voodoo tribe who had cursed Scrooge, seeking revenge for the destruction of his village and the taking of his tribe's lands by Scrooge decades ago.
Scrooge privately admitted to his nephews that he had used an army of "cutthroats" to get the tribe to abandon their lands, in order to establish a rubber plantation. The event was placed by Carl Barks in 1879 during the story, but it would later be retconned by Don Rosa to 1909 to fit with Scrooge's later-established personal history.
The second figure was Bombie the Zombie, the organ of the sorcerer's curse and revenge. He had reportedly sought Scrooge for decades before reaching Duckburg, mistaking Donald for Scrooge.
Barks, with a note of skepticism often found in his stories, explained the zombie as a living person who has never died, but has somehow gotten under the influence of a sorcerer. Although some scenes of the story were intended as a parody of Bela Lugosi's White Zombie, the story is the first to not only focus on Scrooge's past but also touch on the darkest aspects of his personality.
Later stories
Trail of the Unicorn,[11] first published in February 1950, introduced Scrooge's private zoo. One of his pilots had managed to photograph the last living unicorn, which lived in the Indian part of the Himalayas. Scrooge offered a reward to competing cousins Donald Duck and Gladstone Gander, which would go to the one who captured the unicorn for Scrooge's collection of animals.
This was also the story that introduced Scrooge's private airplane. Barks would later establish Scrooge as an experienced aviator. Donald had previously been shown as a skilled aviator, as was Flintheart Glomgold in later stories. In comparison, Huey, Dewey, and Louie were depicted as only having taken flying lessons in the story Frozen Gold (published in January 1945).
The Pixilated Parrot, first published in July 1950, introduced the precursor to Scrooge's money bin; in this story, Scrooge's central office building is said to contain "three cubic acres of money". Two nameless burglars who briefly appear during the story are considered to be the precursors of the Beagle Boys.[12]
Scrooge as a major character
The Magic Hourglass, first published in September 1950, was arguably the first story to change the focus of the Duck stories from Donald to Scrooge. During the story, several themes were introduced for Scrooge.
Donald first mentions in this story that his uncle practically owns Duckburg, a statement that Scrooge's rival John D. Rockerduck would later put in dispute. Scrooge first hints that he was not born into wealth, as he remembers buying the Hourglass in Morocco when he was a member of a ship's crew as a cabin boy. It is also the first story in which Scrooge mentions speaking another language besides his native English and reading other alphabets besides the Latin alphabet, as during the story, he speaks Arabic and reads the Arabic alphabet.
The latter theme would be developed further in later stories. Barks and current Scrooge writer Don Rosa have depicted Scrooge as being fluent in Arabic, Dutch, German, Mongolian, Spanish, Mayan, Bengali, Finnish, and a number of Chinese dialects. Scrooge acquired this knowledge from years of living or traveling to the various regions of the world where those languages are spoken. Later writers would depict Scrooge having at least working knowledge of several other languages.
Scrooge was shown in The Magic Hourglass in a more positive light than in previous stories, but his more villainous side is present too. Scrooge is seen in this story attempting to reacquire a magic hourglass that he gave to Donald, before finding out that it acted as a protective charm for him. Scrooge starts losing one billion dollars each minute, and comments that he will go bankrupt within 600 years. This line is a parody of Orson Welles's line in Citizen Kane "You know, Mr.Thatcher, at the rate of a million dollars a year, I'll have to close this place in ... 60 years".[13] To convince his nephews to return it, he pursues them throughout Morocco, where they had headed to earlier in the story. Memorably during the story, Scrooge interrogates Donald by having him tied up and tickled with a feather in an attempt to get Donald to reveal the hourglass's location. Scrooge finally manages to retrieve it, exchanging it for a flask of water, as he had found his nephews exhausted and left in the desert with no supplies. As Scrooge explains, he intended to give them a higher offer, but he just could not resist having somebody at his mercy without taking advantage of it.
Final developments
A Financial Fable, first published in March 1951, had Scrooge teaching Donald some lessons in productivity as the source of wealth, along with the laws of supply and demand. Perhaps more importantly, it was also the first story where Scrooge observes how diligent and industrious Huey, Louie and Dewey are, making them more similar to himself rather than to Donald. Donald in Barks's stories is depicted as working hard on occasion, but given the choice often proves to be a shirker. The three younger nephews first side with Scrooge rather than Donald in this story, with the bond between granduncle and grandnephews strengthening in later stories. However, there have been rare instances where Donald proved invaluable to Scrooge, such as when the group traveled back in time to Ancient Egypt to retrieve a pharaoh's papyrus. Donald cautions against taking it with him, as no one would believe the story unless it was unearthed. Donald then buries it and makes a marking point from the Nile River, making Scrooge think to himself admiringly, "Donald must have swallowed the Encyclopædia Britannica!"
Terror of the Beagle Boys, first published in November 1951, introduced the readers to the Beagle Boys, although Scrooge in this story seems to be already familiar with them. The Big Bin on Killmotor Hill introduced Scrooge's money bin, built on Killmotor Hill in the center of Duckburg.
By this point, Scrooge had become familiar to readers in the United States and Europe. Other Disney writers and artists besides Barks began using Scrooge in their own stories, including Italian writer Romano Scarpa. Western Publishing, the then-publisher of the Disney crafty comics, started thinking about using Scrooge as a protagonist rather than a supporting character, and then decided to launch Scrooge in his own self-titled comic. Uncle Scrooge #1, featuring the story Only a Poor Old Man, was published in March 1952. This story along with Back to the Klondike, first published a year later in March 1953, became the biggest influences in how Scrooge's character, past, and beliefs would become defined.
After this point, Barks produced most of his longer stories in Uncle Scrooge, with a focus mainly on adventure, while his ten-page stories for Walt Disney's Comics and Stories continued to feature Donald as the star and focused on comedy. In Scrooge's stories, Donald and his nephews were cast as Scrooge's assistants, who accompanied Scrooge in his adventures around the world. This change of focus from Donald to Scrooge was also reflected in stories by other contemporary writers. Since then, Scrooge remains a central figure of the Duck comics' universe, thus the coining of the term "Scrooge McDuck Universe".
Modern era
After Barks's retirement, the character continued under other artists. In 1972, Barks was persuaded to write more stories for Disney. He wrote Junior Woodchuck stories where Scrooge often plays the part of the villain, closer to the role he had before he acquired his own series. Under Barks, Scrooge always was a malleable character who would take on whatever persona was convenient to the plot.
The Italian writer and artist Romano Scarpa made several additions to Scrooge McDuck's universe, including characters such as Brigitta McBridge, Scrooge's self-styled fiancée, and Gideon McDuck, a newspaper editor who is Scrooge's brother. Those characters have appeared mostly in European comics. So is also the case for Scrooge's rival John D. Rockerduck (created by Barks for just one story) and Donald's cousin Fethry Duck, who sometimes works as a reporter for Scrooge's newspaper.
Another major development was the arrival of writer and artist Don Rosa in 1986 with his story "The Son of the Sun", released by Gladstone Publishing and nominated for a Harvey Award, one of the comics industry's highest honors. Rosa has said in interviews that he considers Scrooge to be his favorite Disney character. Unlike most other Disney writers, Don Rosa considered Scrooge as a historical character whose Disney adventures had occurred in the fifties and sixties and ended (in his undepicted death[14]) in 1967 when Barks retired. He considered only Barks' stories canonical, and fleshed out a timeline as well as a family tree based on Barks' stories. Eventually he wrote and drew The Life and Times of Scrooge McDuck, a full history in twelve chapters which received an Eisner Award in 1995. Later editions included additional chapters. Under Rosa, Scrooge became more ethical; while he never cheats, he ruthlessly exploits any loopholes. He owes his fortune to his hard work and his money bin is "full of souvenirs" since every coin reminds him of a specific circumstance. Rosa remains the foremost contemporary duck artist and has been nominated for five 2007 Eisner Awards. His work is regularly reprinted by itself as well as along with Barks stories for which he created a sequel.
Daan Jippes, who can mimic Barks's art to a close extent, repenciled all of Barks's 1970s Junior Woodchucks stories, as well as Barks' final Uncle Scrooge stories, from the 1990s to the early 2000s. Other notable Disney artists who have worked with the Scrooge character include Marco Rota, William Van Horn, and Tony Strobl.
In an interview with the Norwegian "Aftenposten" from 1992 Don Rosa says that "in the beginning Scrooge [owed] his existence to his nephew Donald, but that has changed and today it's Donald that [owes] his existence to Scrooge" and he also says that this is one of the reasons why he is so interested in Scrooge.
Characterization
Wealth

The character is almost exclusively portrayed as having worked his way up the financial ladder from humble immigrant roots.
The comic book series The Life and Times of Scrooge McDuck, written and drawn by Don Rosa, shows Scrooge as a young boy, he took up a job polishing and shining boots in his native Glasgow. A pivotal moment comes when a ditchdigger pays him with an 1875 US dime, which was useless as currency in 19th century Glasgow. Enraged, Scrooge vowed to never be taken advantage of again, to be "sharper than the sharpies and smarter than the smarties." He takes a position as cabin boy on a Clyde cattle ship to the United States to make his fortune at the age of 13. In 1898, after many adventures he finally ends up in Klondike, where he finds a golden rock the size of a goose's egg. By the following year he had made his first $1,000,000 and bought the deed for Killmule Hill from Casey Coot, the son of Clinton Coot and grandson of Cornelius Coot, the founder of Duckburg. He finally ends up in Duckburg in 1902. After some dramatic events where he faces both the Beagle Boys and president Roosevelt and his "Rough Riders" at the same time, he tears down the rest of the old fort Duckburg and builds his famous Money Bin at the site.
In the years to follow, Scrooge travels all around the world in order to increase his fortune, while his family remained behind to manage the Money Bin. When Scrooge finally returns to Duckburg, he is the richest duck in the world, rivaled only by Flintheart Glomgold, John D. Rockerduck, and less prominently, the maharaja of the fictional country Howdoyoustan (play on Hindustan). His experiences, however, had changed him into a hostile miser, and he made his own family leave. Some 12 years later, he closed his empire down, but eventually returned to a public life five years later and started his business.
He keeps the majority of his wealth in a massive Money Bin overlooking the city of Duckburg. In the short Scrooge McDuck and Money, he remarks to his nephews that this money is "just petty cash". In the Dutch and Italian version he regularly forces Donald and his nephews to polish the coins one by one in order to pay off Donald's debts; Scrooge will not pay them much for this lengthy, tedious, hand-breaking work. As far as he is concerned, even 5 cents an hour is too much expenditure.
A shrewd businessman and noted tightwad, he is fond of diving into and swimming in his money, without injury. He is also the richest member of The Billionaires Club of Duckburg, a society which includes the most successful businessmen of the world and allows them to keep connections with each other. Glomgold and Rockerduck are also influential members of the Club. His most famous prized possession is his Number One Dime.

The sum of Scrooge's wealth is unclear.[15] According to Barks' The Second Richest Duck as noted by a Time article, Scrooge is worth "one multiplujillion, nine obsquatumatillion, six hundred twenty-three dollars and sixty-two cents".[16] In the DuckTales episode "Liquid Assets", Fenton Crackshell (Scrooge's accountant) notes that McDuck's money bin contains "607 tillion 386 zillion 947 trillion 522 billion dollars and 36 cents". Don Rosa's Life and Times of Scrooge McDuck notes that Scrooge amounts to "five multiplujillion, nine impossibidillion, seven fantastica trillion dollars and sixteen cents". A thought bubble from Scrooge McDuck sitting in his car with his chauffeur in Walt Disney's Christmas Parade No.1 (published in 1949) that takes place in the story "Letter to Santa" clearly states "What's the use of having 'eleven octillion dollars' if I don't make a big noise about it?" In DuckTales the Movie: Treasure of the Lost Lamp, Scrooge mentions "We quadzillionaires have our own ideas of fun." In the first episode of the 2017 DuckTales series, Scrooge states that he runs "a multi-trillion dollar business".
Forbes magazine has occasionally tried to estimate Scrooge's wealth in real terms; in 2007, the magazine estimated his wealth at $28.8 billion;[17] in 2011, it rose to $44.1 billion due to the rise in gold prices.[18] Another, more in-depth analysis of Scrooge's wealth was done by MatPat of The Film Theory channel on YouTube. Using 4 different methodologies to calculate the volume of actual gold in Scrooge's money bin (depth gauge, ladder length, blueprints, and 3 cubic acres), the four amounts from most conservative to "more money than the entire planet Earth" the amounts were: $52,348,493,767.50 (depth gauge), $239,307,400,080 (ladder), $12,434,013,552,490 (blueprints), $333,927,633,863,527 (3 cubic acres); with each valuation based on a then current gold price of $1243.30 per troy ounce.[19] Whatever the amount, Scrooge never considers it to be enough; he believes that he has to continue to earn money by any means possible. A running gag is Scrooge always making profit on any business deal.[20]
Education
Scrooge never completed a formal education, as he left school at an early age. However, he has a sharp mind and is always ready to learn new skills. Because of his secondary occupation as a treasure hunter, Scrooge has become something of a scholar and an amateur archaeologist. Starting with Barks, several writers have explained how Scrooge becomes aware of the treasures he decides to pursue. This often involves periods of research consulting various written sources in search of passages that might lead him to a treasure. Often Scrooge decides to search for the possible truth behind old legends, or discovers obscure references to the activities of ancient conquerors, explorers and military leaders that he considers interesting enough to begin a new expedition.
As a result of his research, Scrooge has built up an extensive personal library, which includes many rare tomes. In Barks's and Rosa's stories, among the prized pieces of this library is an almost complete collection of Spanish and Dutch naval logs of the 16th and 17th centuries. Their references to the fates of other ships have often allowed Scrooge to locate sunken ships and recover their treasures from their watery graves. Mostly self-taught as he is, Scrooge is a firm believer in the saying "knowledge is power". Scrooge is also an accomplished linguist and entrepreneur, having learned to speak several different languages during his business trips around the world, selling refrigerators to Eskimos, wind to windmill manufacturers in the Netherlands, etc.
Morality and beliefs
Both as a businessman and as a treasure hunter, Scrooge is noted for his drive to set new goals and face new challenges. As Carl Barks described his character, for Scrooge there is "always another rainbow". The phrase later provided the title for one of Barks's better-known paintings depicting Scrooge. Periods of inactivity between adventures and lack of serious challenges tend to be depressing for Scrooge after a while; some stories see these phases take a toll on his health. Scrooge's other motto is "Work smarter, not harder."
As a businessman, Scrooge often resorts to aggressive tactics and deception. He seems to have gained significant experience in manipulating people and events towards his own ends. As often seen in stories by writer Guido Martina and occasionally by others, Scrooge is noted for his cynicism, especially towards ideals of morality when it comes to business and the pursuit of set goals. This has been noted by some as not being part of Barks's original profile of the character, but has since come to be accepted as one valid interpretation of Scrooge's way of thinking.
Scrooge seems to have a personal code of honesty that offers him an amount of self-control. He can often be seen contemplating the next course of action, divided between adopting a ruthless pursuit of his current goal against those tactics he considers more honest. At times, he can sacrifice his goal in order to remain within the limits of this sense of honesty. Several fans of the character have come to consider these depictions as adding to the depth of his personality, because based on the decisions he takes Scrooge can be both the hero and the villain of his stories. This is one thing he has in common with his nephew Donald. Scrooge's sense of honesty also distinguishes him from his rival Flintheart Glomgold, who places no such self-limitations. During the cartoon series DuckTales, at times he would be heard saying to Glomgold, "You're a cheater, and cheaters never prosper!"
Scrooge has a volatile temper and rarely hesitates to use cartoon violence against those who provoke his ire (often his nephew Donald, but also bill and tax collectors as well as door-to-door salesmen); however, he seems to be against the use of lethal force. On occasion, he has even saved the lives of enemies who had threatened his own life but were in danger of losing their own. According to Scrooge's own explanation, this is to save himself from feelings of guilt over their deaths; he generally awaits no gratitude from them. Scrooge has also opined that only in fairy tales do bad people turn good, and that he is old enough to not believe in fairy tales. Scrooge believes in keeping his word—never breaking a promise once given.[21] In Italian-produced stories of the 1950s to 1970s, however, particularly those written by Guido Martina, Scrooge often acts differently from in American or Danish comics productions.
Carl Barks gave Scrooge a definite set of ethics which were in tone with the time he was supposed to have made his fortune. The robber barons and industrialists of the 1890–1920s era were McDuck's competition as he earned his fortune. Scrooge proudly asserts "I made it by being tougher than the toughies and smarter than the smarties! And I made it square!" Barks's creation is averse to dishonesty in the pursuit of wealth. When Disney filmmakers first contemplated a Scrooge feature cartoon in the fifties, the animators had no understanding of the Scrooge McDuck character and merely envisioned Scrooge as a duck version of Ebenezer Scrooge—a very unsympathetic character. In the end they shelved the idea because a duck who gets all excited about money just was not funny enough.
In an interview, Barks summed up his beliefs about Scrooge and capitalism:
I've always looked at the ducks as caricatured human beings. In rereading the stories, I realized that I had gotten kind of deep in some of them: there was philosophy in there that I hadn't realized I was putting in. It was an added feature that went along with the stories. I think a lot of the philosophy in my stories is conservative—conservative in the sense that I feel our civilization peaked around 1910. Since then we've been going downhill. Much of the older culture had basic qualities that the new stuff we keep hatching can never match.
Look at the magnificent cathedrals and palaces that were built. Nobody can build that sort of thing nowadays. Also, I believe that we should preserve many old ideals and methods of working: honor, honesty, allowing other people to believe in their own ideas, not trying to force everyone into one form. The thing I have against the present political system is that it tries to make everybody exactly alike. We should have a million different patterns.
They say that wealthy people like the Vanderbilts and Rockefellers are sinful because they accumulated fortunes by exploiting the poor. I feel that everybody should be able to rise as high as they can or want to, provided they don't kill anybody or actually oppress other people on the way up. A little exploitation is something you come by in nature. We see it in the pecking order of animals—everybody has to be exploited or to exploit someone else to a certain extent. I don't resent those things.[22]

Personality
Scrooge is very misunderstood. In his early years, he was very friendly and generous. But the 'slaps' of society from cruel people, as well as the ungratefulness of those who he had helped to overcome their problems, made Scrooge bitter, grumpy, and arrogant.  Feeling that he had been taken advantage of, he didn't want to believe that others had real problems or difficulties in their lives.  This made him seem out-of-touch at best, and selfish at worst.  As a result, no one could understand his problems, including his nephew, and his great-nephews. This isolation paved the path to acquiring untold wealth and power. But despite it all, he is very loyal, and will help those he sees as in-peril or need of help.
DuckTales

In the DuckTales series, Scrooge has adopted the nephews (as Donald has joined the Navy and is away on his tour of duty), and as a result his darker personality traits are downplayed. While most of his persona remain from the comics, he is notably more optimistic and less hot-headed in the animated cartoon. In an early episode, Scrooge credits his improved temperament to the nephews and Webby (his housekeeper's granddaughter, who comes to live in Scrooge's mansion), saying that "for the first time since I left Scotland, I have a family". Though Scrooge is far from tyrannical in the comics, he is rarely so openly affectionate. While he still hunts for treasure in DuckTales, many episodes focus on his attempts to thwart villains. However, he remains just as tightfisted with money as he has always been. But he's also affable and patient with his family and friends.
Scrooge displays a strict code of honor, insisting that the only valid way to acquire wealth is to "earn it square," and he goes to great lengths to thwart those (sometimes even his own nephews) who gain money dishonestly. This code also prevents him from ever being dishonest himself, and he avows that "Scrooge McDuck's word is as good as gold." He also expresses great disgust at being viewed by others as a greedy liar and cheater.
The series fleshes out Scrooge's upbringing by depicting his life as an individual who worked hard his entire life to earn his keep and to fiercely defend it against those who were truly dishonest but also, he defends his family and friends from any dangers, including villains. His value teaches his nephews not to be dishonest with him or anybody else. It is shown that money is no longer the most important thing in his life. For one episode, he was under a love spell, which caused him to lavish his time on a goddess over everything else. The nephews find out that the only way to break the spell is make the person realize that the object of their love will cost them something they truly love. The boys make it appear that Scrooge's love is allergic to money; however, he simply decides to give up his wealth so he can be with her. Later, when he realizes he will have to give up his nephews to be with her, the spell is immediately broken, showing that family is the most important thing to him.
On occasion, he demonstrates considerable physical strength by single-handedly beating bigger foes. He credits his robustness to "lifting money bags."
Europe
Many of the European comics based on the Disney Universe have created their own version of Scrooge McDuck, usually involving him in slapstick adventures. This is particularly true of the Italian comics which were very popular in the 1960s–1980s in most parts of Western continental Europe. In these, Scrooge is mainly an anti-hero dragging his long-suffering nephews into treasure hunts and shady business deals. Donald is a reluctant participant in these travels, only agreeing to go along when his uncle reminds him of the debts and back-rent Donald owes him, threatens him with a sword or blunderbuss, or offers a share of the loot. When he promises Donald a share of the treasure, Scrooge will add a little loophole in the terms which may seem obscure at first but which he brings up at the end of the adventure to deny Donald his share, keeping the whole for himself. After Donald risks life and limb – something which Scrooge shows little concern for – he tends to end up with nothing.
Another running joke is Scrooge reminiscing about his adventures while gold prospecting in the Klondike much to Donald and the nephews' chagrin at hearing the never-ending and tiresome stories.
Age
According to Carl Barks' 1955 one-pager "Watt an Occasion" (Uncle Scrooge #12), Scrooge is 75 years of age. According to Don Rosa, Scrooge was born in Scotland in 1867, and earned his Number One Dime (or First Coin) exactly ten years later. The DuckTales episodes (and many European comics) show a Scrooge who hailed from Scotland in the 19th century, yet was clearly familiar with all the technology and amenities of the 1980s. Despite this extremely advanced age, Scrooge does not appear to be on the verge of dotage, and is vigorous enough to keep up with his nephews in adventures; with rare exception, there appears to be no sign of him slowing down.
Barks responded to some fan letters asking about Scrooge's Adamic age, that in the story "That's No Fable!", when Scrooge drank water from a Fountain of Youth for several days, rather than making him young again (bodily contact with the water was required for that), ingesting the water rejuvenated his body and cured him of his rheumatia, which arguably allowed Scrooge to live beyond his expected years with no sign of slowdown or senility. Don Rosa's solution to the issue of Scrooge's age is that he set all of his stories in the 1950s or earlier, which was when he himself discovered and reveled in Barks' stories as a kid, and in his unofficial timelines, he had Scrooge die in 1967, at the age of 100 years.
In the 15th Episode of the 2017 DuckTales reboot, it is revealed that Scrooge was also "stuck in a timeless demon dimension" called Demogorgana for an unknown amount of time, which is used to explain his young look.[23]
In popular culture
Cultural impact
Forbes magazine routinely lists Scrooge McDuck on its annual "Fictional 15" list of the richest fictional characters by net worth:

2002: #4 with $8.2 billion[24]
2005: #6 with $8.2 billion[25]
2006: #3 with $10.9 billion[26]
2007: #1 with $28.8 billion (₤17.6 billion)[27]
2008: #2 with $29.1 billion[28]
2010: #2 with $33.5 billion[29]
2011: #1 with $44.1 billion[30]
2013: #1 with $65.4 billion[31]
Grupo Ronda S.A has the license to use the character, as well as other Disney characters in the board game Tío Rico Mc. Pato from 1972 to the present. Being one of the most popular board games in Colombia and being the direct competitor of Monopoly in the region.[32]
In tribute to its famous native, Glasgow City Council added Scrooge to its list of "Famous Glaswegians" in 2007, alongside the likes of Billy Connolly and Charles Rennie Mackintosh.[33]
In 2008 The Weekly Standard parodied the bailout of the financial markets by publishing a memo where Scrooge applies to the TARP program.[34]
An extortionist named Arno Funke targeted German department store chain Karstadt from 1992 until his capture in 1994, under the alias "Dagobert", the German (first) name for Scrooge McDuck.[35]
In the Family Guy episode "Lottery Fever", Peter injures himself trying to dive into a pile of coins like Scrooge McDuck.
In the 2013 episode of Breaking Bad, "Buried", Saul Goodman associate Patrick Kuby remarks to fellow associate Huell Babineaux "we are here to do a job, not channel Scrooge McDuck" when Huell lays down on Walter White's pile of cash stored in a storage facility locker.
Dagobertducktaks ("Dagobert Duck" is the Dutch name for Scrooge McDuck), a tax for the wealthy, was elected Dutch word of the year 2014 in a poll by Van Dale.[36][37]
In August 2017, the YouTube channel "The Film Theorists", hosted by Matthew "MatPat" Patrick, estimated the worth of the gold coins in the money bin of Scrooge McDuck based on four sources, with the lowest source equaling $52,348,493,767.50 and the highest source ("three cubic acres") equaling $333,927,633,863,527.10 of gold value.[38]
Scrooge McDuck Universe

The popularity of Scrooge McDuck comics spawned an entire mythology around the character, including new supporting characters, adventures, and life experiences as told by numerous authors. The popularity of the Duck universe – the fandom term for the associated intellectual properties that have developed from Scrooge's stories over the years, including the city of Duckburg – has led Don Rosa to claim that "in the beginning Scrooge [owed] his existence to his nephew Donald, but that has changed and today it's Donald that [owes] his existence to Scrooge."
In addition to the many original and existing characters in stories about Scrooge McDuck, authors have frequently led historical figures to meet Scrooge over the course of his life. Most notably, Scrooge has met US president Theodore Roosevelt. Roosevelt and Scrooge would meet each other at least three times: in the Dakotas in 1883, in Duckburg in 1902, and in Panama in 1906. See Historical Figures in Scrooge McDuck stories.
Based on writer Don Rosa's The Life and Times of Scrooge McDuck, a popular timeline chronicling Scrooge's adventures was created consisting of the most important "facts" about Scrooge's life. See Scrooge McDuck timeline according to Don Rosa.
In 2014, composer Tuomas Holopainen of Nightwish released a conceptual album based on the book, The Life and Times of Scrooge McDuck. The album is titled Music Inspired by the Life and Times of Scrooge. Don Rosa illustrated the cover artwork for the album.[39]
In other media
The character of Scrooge has appeared in various mediums aside from comic books. Scrooge's voice was first heard on the 1960 record album Donald Duck and His Friends; Dal McKennon voiced the character for this appearance.[40] Scrooge's first appearance in animated form (save for a brief Mickey Mouse Club television series cameo) was in Disney's 1967 theatrical short Scrooge McDuck and Money (voiced by Bill Thompson), in which he teaches his nephews basic financial tips.[41]
In 1974, Disneyland Records released an adaptation of the Charles Dickens classic A Christmas Carol, for which Alan Young was hired to voice Scrooge McDuck playing the character who inspired his name, Ebenezer Scrooge (Thompson had died in 1971). Young, who himself was born in Great Britain, was best known for playing Wilbur Post on the hit television series Mister Ed from 1961 to 1965. Eight years later, the Walt Disney Animation Studios decided to make a featurette of this same story, this time dubbed Mickey's Christmas Carol (1983), and once again hired Young to voice the role.[40][42] He also appeared as himself in the television special Sport Goofy in Soccermania (1987) (the only time when he was voiced by Will Ryan).
Scrooge's biggest role outside comics would come in the 1987 animated series DuckTales, a series loosely based on Carl Barks's comics, and where Alan Young returned to voice his character. In this series, premiered over two-hours on September 18, 1987, while the regular episodes began three days later, Scrooge becomes the legal guardian of Huey, Dewey and Louie when Donald joins the United States Navy. Scrooge's DuckTales persona is considerably mellow compared to most previous appearances; his aggression is played down and his often duplicitous personality is reduced in many episodes to that of a curmudgeonly but well-meaning old uncle. Still, there are flashes of Barks' Scrooge to be seen, particularly in early episodes of the first season. Scrooge also appeared in DuckTales the Movie: Treasure of the Lost Lamp, released during the series' run. He was mentioned in the Darkwing Duck episode "Tiff of the Titans", but never really seen.
He has appeared in some episodes of Raw Toonage, two shorts of Mickey Mouse Works and some episodes (specially "House of Scrooge") of Disney's House of Mouse, as well as the direct-to-video films Mickey's Once Upon a Christmas and Mickey's Twice Upon a Christmas. His video game appearances include the three DuckTales releases (DuckTales, DuckTales 2, and DuckTales: The Quest for Gold), and in Toontown Online as the accidental creator of the Cogs. Additionally, he is a secret playable character in 2008 quiz game, Disney TH!NK Fast. In the 2012 Nintendo 3DS game Epic Mickey: Power of Illusion, he is one of the first characters Mickey rescues, running a shop in the fortress selling upgrades and serving as a Sketch summon in which he uses his cane pogostick from the Ducktales NES games.
In 1961 a 45rpm single record was released entitled "Donald Duck and Uncle Scrooge's Money Rocket" (aka "Uncle Scrooge's Rocket to the Moon"), a story of how Scrooge builds a rocket to send all his money to the moon to protect it from the "Beagle Boys".

Scrooge also makes an appearance in Disney's and Square Enix's Kingdom Hearts series, in a role where he helps Mickey Mouse set up a world transit system. He first appears in Kingdom Hearts II as a minor non-playable character in Hollow Bastion, where he is trying to recreate his favorite ice cream flavor – sea-salt.[43] Scrooge later appears in the prequel, Kingdom Hearts: Birth by Sleep, this time with a speaking role. He works on establishing an ice-cream business in Radiant Garden and gives Ventus three passes to the Dream Festival in Disney Town. Young reprises the role in the English version of Birth by Sleep.
Scrooge has appeared in the Boom! Studios Darkwing Duck comic, playing a key role at the end of its initial story, "The Duck Knight Returns". Later he would also play a key role on the final story arc "Dangerous Currency", where he teams up with Darkwing Duck in order to stop the Phantom Blot and Magica De Spell from taking over St. Canard and Duckburg.
In 2015, Scrooge was seen in the Mickey Mouse short "Goofy's First Love", where Mickey and Donald are trying to help Goofy find his love. Donald suggests money, and they head over to Scrooge's mansion where Donald tells his uncle that Goofy needs a million dollars. Scrooge then has his butler kick them out. When Goofy is inadvertently launched from a treadmill and catapulted off another building, he lands in Scrooge's mansion. The butler kicks Goofy out and the process repeats itself but this time Mickey and Donald are catapulted as well and kicked out by the butler. Scrooge is seen at the end attending Goofy's wedding with a sandwich. In the 2016 Mickey Mouse Christmas special, "Duck the Halls", after Young's death, John Kassir took over voicing Scrooge McDuck, however he later tweeted that he won't be reprising his role in the reboot. Kassir continues to voice the character in subsequent appearances in this series. Scrooge makes a cameo appearance in the Legend of the Three Caballeros episode "Shangri-La-Di-Da", voiced by Eric Bauza.
In the new DuckTales, Scrooge is played by Scottish actor David Tennant, who brings both the nephews and Donald into his home at the end of the series premier.[44] This series shows that Scrooge previously adventured with his nephew Donald and his niece Della Duck, but a tragic event ten years prior to the start of the series resulted in Scrooge and Donald going their separate ways. He seems to have a rather pessimistic attitude about family as a result, and is initially reluctant in spending time with the boys until they assist him in a couple of adventures.
See also

Clan McDuck
List of fictional ducks
The Life and Times of Scrooge McDuck – with a timeline
Music Inspired by the Life and Times of Scrooge
Uncle Scrooge comic book
Notes

Further reading
Uncle Scrooge McDuck, Carl Barks, Edward Summer, Walt Disney Productions 1981 ISBN0-89087-290-2
The Carl Barks Library, Another Rainbow Publishing 1984
Scrooge McDuck Capitalist and Proud of it!, Goldbrick & Bond, USA-International Publications 2004
How to Read Donald Duck: Imperialist Ideology in the Disney Comic, Dorfman & Mattelart, International General 1975
, Scroogiefan.com
, University Press of Mississippi, Thomas Andrae 2006 ISBN1-57806-858-4
, Jack Chalker, Mirage Press 1974 ISBN0-88358-502-2

  at the INDUCKS

 Carl Barks and Don Rosa's stories and characters database (in English) (in French)

When was the character Scrooge McDuck first introduced?