Linkage and Gene Mapping

Linkage refers to the presence of two different genes on the same chromosome . Two genes that occur on the same chromosome are said to be linked, and those that occur very close together are tightly linked. Study of linkage provides information about the relative position of genes on chromosomes, allowing the construction of chromosome maps.

Basic Concepts
Different forms of the same gene, called alleles , are present on matching, or homologous, chromosomes in similar positions, or loci. For instance, in Gregor Mendel's experiments with peas, green and yellow are two alleles for pod color. In a heterozygote, which has both alleles, the two alleles occupy the same loci on homologous chromosomes. Similarly, round and wrinkled are alleles for seed texture. In the pea, these two genespod color and seed textureare on different pairs of homologs and are therefore not linked. When gametes form in double heterozygotes (for example, a green/yellowround/wrinkled plant), these genes assort independently, because the two chromosomes that bear them assort independently. Therefore, meiosis will create equal numbers of green-round, green-wrinkled, yellow-round, and yellow-wrinkled gametes. Mating between double heterozygotes (called a dihybrid cross) will give a characteristic ratio of the different possible plant types. However, if the two traits were located close to one another on the same chromosome in other words, if they were linkedthe observed ratio will be quite different from that seen for unlinked traits. Allele combinations that began together (for instance, roundgreen) will tend to stay together, and the offspring will show a skewed ratio reflecting the original combinations. Despite being on the same chromosome, the round and green alleles could become separated during meiosis by crossing over, a form of genetic recombination. During crossing over, homologous chromosomes exchange segments. This could allow the

yellow allele to switch places with the green allele and lead to a round-yellow gamete. If the loci for the two genes are very close, crossing over is unlikely to separate alleles, whereas if they are far apart, crossing over is much more likely to separate them. Therefore, the frequency of crossing over is related to the physical distance between the loci for the two genes. The particular combination of alleles on the homologous chromosomes in the dihybrid parent (for example, round-green) is known as linkage phase. Separation of this combination by crossing over is said to be a change in phase. The two alleles of a particular gene are said to be markers for that site of the chromosome.

Linkage in Fruit Flies

An example of using linkage to explore gene position is provided by inheritance of eye color and body color in fruit flies, both of which are located on the X chromosome. This example begins with purebred (homozygous) parents, one yellow-bodied and red-eyed, the other grey-bodied and white-eyed. They mate to produce all heterozygous daughters, who carry the yellow-red combination on one homologous chromosome and the grey-white combination on the other. When the heterozygotes create gametes, the eye-color alleles cannot assort independently from the body-color alleles because they are linked. Some crossing over can occur, though. As in humans, male fruit flies carry only one X chromosome, and so will show exactly what alleles are present on their X. When one counts the male offspring, approximately 49.5 percent are yellow-bodied and red-eyed, 49.5

Crossing over between homologous chromosomes creates new combinations of alleles. percent are grey-bodied and white-eyed, 0.5 percent are yellow-bodied and white-eyed, and 0.5 percent are grey-bodied and red-eyed. This indicates very tight linkageclose proximityof the two genes.

In this example, the yellow-body allele and the white-eye allele are said to be "out of phase" in the parental strains. The most frequent pair of gamete types are described as "parental types" because they retain the alleles for the two genes as transmitted by the original parent strains. The two gamete types that are less frequent are the "recombinant types," which results only from an exchange or crossover of homologous chromosomes in the interval between the genes.

Gene Mapping
As an undergraduate in 1913, A. H. Sturtevant wrote a brilliant paper that extended linkage analysis into gene mapping. Sturtevant analyzed numerous linkage experiments in the fruit fly, each using two genes. For instance, a similar experiment with body color

and wing shape shows many more outof-phase offspring, indicating the wing-shape gene is further from the bodycolor

Three fruit fly genes on the same chromosome show different levels of separation during crossover, proportional to the distance between them. gene than the eye-color gene is. Another experiment showed an intermediate number of out-ofphase offspring for eye color and wing shape. This allowed Sturtevant to reason that the bodycolor gene and wing shape gene are furthest apart, with eye color in between them.

Extension of this technique allowed the distance between genes to be expressed as map units. One map unit is defined as the effective distance needed to obtain a 1 percent recombination between linked alleles. The map unit is also called the centiMorgan (cM), to honor T. H. Morgan, Sturtevant's teacher and one of the founders of chromosomal genetics. Because crossing over is not equally likely between any two points, map units do not correspond directly to number of nucleotides along the DNA double helix. Sturtevant's work helped show that the chromosome is a linear sequence of genes. Gene mapping determines the position and order of genes relative to other genes along the chromosome. A well-marked linkage group extends from markers located at one end of the chromosome to those in the middle, and on to markers located at the other end. The number of linkage groups for an organism is equal to its number of homologous chromosome pairs.

Modern Applications
Sturtevant's discovery led to the golden age of chromosome transmission genetics, with an emphasis on identifying genes through alleles with visible phenotypes , and using them as markers for determining their position on the linkage map. Since then the

emphasis in genetics has shifted to understanding the functions of genes. Linkage and gene mapping studies have progressed to being a critical tool in cloning genes and providing more description of their roles in the organism. These approaches include:

Using map locations to distinguish different genes with similar sequences, mutant phenotypes, or functions. Examples are the cell division cycle mutants of the yeast Saccharomyces cercvisiae or the uncoordinated mutants of the roundworm C. elegans. In some cases mutants with different phenotypes have been shown to be done to different mutations in the same gene, as is the case with the Drosophila circadian rhythm period mutants termed short, long, and none (per[S], per[L] and per[0]).

Using map locations to track down genes to clone their deoxyribonucleic acid (DNA) by chromosome position. Examples are the human cystic fibrosis transmembrane regulator gene mutated in cystic fibrosis, or the polyglutamine repeat gene that is mutated in Huntington's disease. With genome sequences available on databases, mapping mutant phenotypes points to candidate loci for the gene at the chromosome position.

New classes of markers in linkage analysis are based on naturally occurring DNA variation in the genome , and have many advantages. These variations are usually harmless and don't interrupt a gene, so there is no selection against them, meaning they persist over many generations. They are quite numerous and are distinguished throughout in the genome. Individuals are likely to be heterozygous from many of them and therefore the markers are informative for linkage. If the DNA variant is present heterozygously, can be detected, and shows Mendelian segregation, it is as good a linkage marker as yellow bodies or white eyes. The disadvantage is that analysis to detect the variant is sometimes more laborious and requires the techniques of molecular biology. The common types of DNA markers and the molecular techniques used to follow their inheritance are:

Restriction fragment length polymorphisms (RFLPs) are derived from sequence variation that results in the loss of a restriction enzyme digestion site. The result is a longer fragment of the DNA from that location following digestion with that enzyme. A

heterozygous parent will transmit either the allele specifying the long fragment or the allele specifying the short fragment to each child. After size separation of DNA fragments by gel electrophoresis and transfer to a Southern blot, these DNA fragments of interest can be identified with a specific DNA or ribonucleic acid (RNA) probe that also comes from that location. If the long fragment, for example, is linked to a disease gene, the child's DNA can reveal if he or she is likely to develop the disease.

Randomly amplified polymorphic DNAs (RAPDs) are derived from sequence variation that results in the loss of the complementary site to a primer necessary to initiate chain amplification by polymerase chain reaction (PCR). If the DNA used as template contains complementary sites for both primers, a PCR product is obtained that can be detected by gel electrophoresis. If either site is absent or changed in the template no product will be obtained from the reaction.

Human Disease Genes

Human families pose some of the greatest challenges to linkage analysis. Human families are small, and matings are not designed by the needs of genetic analysis. Mapping a mutation that causes a disease usually requires assembling enough families that transmit the mutation in hopes that some of them will be heterozygous, or informative, at some RFLP, RAPD, or other markers that are near enough to the disease gene to show linkage. Instead of determining linkage by counting crossover numbers as Sturtevant did, human genetics uses an alternative means to estimate whether linkage is present between marker and disease gene. This approach is called LOD score analysis, after Log of the Odds for or against linkage. Each child from informative parents is scored as recombinant (R) or parental (P). The total number of R and P results for each family is used to calculate "scores" for the odds that the results are due to linkage at a table of recombination frequencies from 1 cM, 10 cM, 20 cM, etc., relative to the chance that the results came from independent assortment. The logs of the odds scores for each family are added to the log scores of other families to increase the number of independent observations. A LOD score value of 3, representing no more than a 5 percent chance of mistakenly declaring linkage, is the minimum acceptable score for assumption of true linkage between marker and disease gene. The recombination value that gives the highest LOD score over all the families is

the presumptive linkage distance of the disease gene mutation from the adjacent markers. The first human disease gene mapped this way was Huntington's disease, which had a LOD score of over 6 for a recombination distance from its marker of between 5 and 10 cM. Once a marker has been found, it can be used to predict whether any particular family member has inherited the marker and therefore is likely to have inherited the disease gene.
SEE ALSO G ENETIC A NALYSIS ; G ENETIC D ISEASES ; M ENDEL , G REGOR ; P ATTERNS OF I NHERITANCE ; P OLYMERASE C HAIN R EACTION

John Merriam

Bibliography
Alberts, Bruce, et al. Molecular Biology of the Cell, 4th ed. New York: Garland Publishing, 2000. Creighton, Thomas E. Proteins: Structures and Molecular Properties, 2nd ed. New York: W. H. Freeman and Company, 1993. Freifelder, David. Molecular Biology, 2nd ed. Boston: Jones & Bartlett, 1987. Lehninger, Albert L. Principles of Biochemistry, New York: Worth Publishers, 1982.

Read more: Linkage and Gene Mapping - Biology Encyclopedia - plant, body, examples, human, different, chromosomes, DNA, cycle http://www.biologyreference.com/La-Ma/Linkage-andGene-Mapping.html#ixzz1OgddT5aG

----------------------------------------------------------------------------------------------------------------MICROBIOLOGY

Introduction
In this tutorial you will be learning about the Linnaean system of classification

used in the biological sciences to describe and categorize all living things. The focus is on finding out how humans fit within this system. In addition, you will discover part of the great diversity of life forms and come to understand why some animals are considered to be close to us in their evolutionary history.

How many species are there?

This is not an easy question to answer. About 1.8 million have been given scientific names. Nearly 2/3 of these are insects. Estimates of the total number of living species generally range from 10 to 100 million. It is likely the actual number is on the order of 13 to 14 million, with most being insects and microscopic life forms in tropical regions. However, we may never know how many there are because many of them will become extinct before being counted and described. The tremendous diversity in life today is not new to our planet. The noted paleontologist Stephen Jay Gould estimated that 99% of all plant and animal species that have existed have already become extinct with most leaving no fossils. It is also humbling to realize that humans and other large animals are freakishly rare life forms, since 99% of all known animal species are smaller than bumble bees.

Why should we be interested in learning about the diversity of life?

In order to fully understand our own biological evolution, we need to be aware that humans are animals and that we have close relatives in the animal kingdom. Grasping the comparative evolutionary distances between different species is important to this understanding. In addition, it is fun to learn about other kinds of creatures.

When did scientists begin classifying living things?

Before the advent of modern, genetically based evolutionary studies, European and American biology consisted primarily of taxonomy , or classification of organisms into different categories based on their physical characteristics and presumed natural relationship. The leading naturalists of the 18th and 19th centuries spent their lives identifying and naming newly discovered plants and animals. However, few of them asked what accounted for the patterns of similarities and differences between the organisms. This basically nonspeculative approach is not surprising since most naturalists two centuries ago held the view that plants and animals (including humans) had been created in their present form and that they have remained unchanged. As a result, it made no sense to ask how organisms have evolved through time. Similarly, it was inconceivable that two animals or plants may have had a common ancestor or that extinct species may have been ancestors of modern ones.

One of the most important 18th century naturalists was a Swedish botanist and medical doctor named Karl von Linn. He wrote 180 books mainly describing plant species in extreme detail. Since his published writings were mostly in Latin, he is known to the scientific world today as Carolus Linnaeus , which is the Latinized form he chose for his name. In 1735, Linnaeus published an influential book entitled Systema Naturae in which he outlined his scheme for classifying all known Carolus Linnaeus and yet to be discovered organisms according to the greater or 1707-1778 lesser extent of their similarities. This Linnaean system of classification was widely accepted by the early 19th century and is still the basic framework for all taxonomy in the biological sciences today. The Linnaean system uses two Latin name categories, genus and species , to designate each type of organism. A genus is a higher level category that includes one or more species under it. Such a dual level designation is referred to as a binomial nomenclature or binomen (literally "two names" in Latin). For example, Linnaeus described humans in his system with the binomen Homo sapiens , or "man who is wise"--Homo is our genus and sapiens is our species.
genus species species genus species species

Linnaeus also created higher, more inclusive classification categories. For instance, he placed all monkeys and apes along with humans into the order Primates . His use of the word Primates (from the Latin primus meaning "first") reflects the human centered world view of Western science during the 18th century. It implied that humans were "created" first. However, it also indicated that people are animals.
order family genus species species genus species species genus species species family genus species species

While the form of the Linnaean classification system remains substantially the same, the reasoning behind it has undergone considerable change. For Linnaeus and his contemporaries, taxonomy served to rationally demonstrate the unchanging order inherent in Biblical creation and was an end in itself. From this perspective, spending a life dedicated to precisely describing and naming organisms was a religious act because it was revealing the great complexity of life created by God. This static view of nature was overturned in science by the middle of the 19th century by a small number of radical Charles Darwin naturalists, most notably Charles Darwin. He provided 1809-1882 conclusive evidence that evolution of life forms has occurred. In addition, he proposed natural selection as the mechanism responsible for these changes. Late in his life, Linnaeus also began to have some doubts about species being unchanging. Crossbreeding resulting in new varieties of plants suggested to him that life forms could change somewhat. However, he stopped short of accepting the evolution of one species into another.

Why do we classify living things today?

Since Darwin's time, biological classification has come to be understood as reflecting evolutionary distances and relationships between organisms. The creatures of our time have had common ancestors in the past. In a very real sense, they are members of the same family tree. The great diversity of life is largely a result of branching evolution or adaptive radiation. This is the diversification of a species into different lines as they adapt to new ecological niches and ultimately evolve into distinct species. Natural selection is the principal mechanism driving adaptive radiation.

Principles of Classification

Think about an elephant. Develop a mental image of it. How would you describe it to someone who has never seen one? Take a moment to consider carefully . . .

African Elephant

Very likely your mental image was a visual one like the picture. Humans primarily emphasize traits that can be seen with their eyes since they mostly rely on their sense of vision. However, there is no reason that an elephant or any other organism could not be described in terms of touch, smell, and/or sound as well. Think about an elephant again but this time in terms of non-visual traits . . .

Not surprisingly, biologists also classify organisms into different categories mostly by judging degrees of apparent similarity and difference that they can see. The assumption is that the greater the degree of physical similarity, the closer the biological relationship. On discovering an unknown organism, researchers begin their classification by looking for anatomical features that appear to have the same function as those found on other species. The next step is determining whether or not the similarities are due to an independent evolutionary development or to descent from a common ancestor. If the latter is the case, then the two species are probably closely related and should be classified into the same or near biological categories.

Human arm bones Homologies are anatomical features, of different organisms, (a common mammal, bird that have a similar appearance or function because they were and reptile configuration) inherited from a common ancestor that also had them. For instance, the forelimb of a bear, the wing of a bird, and your arm have the same functional types of bones as did our shared reptilian ancestor. Therefore, these bones are homologous structures. The more homologies two organisms possess, the more likely it is that they have a close genetic relationship.

There can also be nonhomologous structural similarities between species. In these cases, the common ancestor did not have the same anatomical structures as its descendants. Instead, the similarities are due to independent development in the now separate evolutionary lines. Such misleading similarities are called homoplasies . Homoplastic structures can be the result of parallelism, convergence, analogies, or mere chance. Parallelism , or parallel evolution, is a similar evolutionary development in different species lines after divergence from a common ancestor that did not have the characteristic but did have an initial anatomical feature that led to it. For instance, some South American and African monkeys evolved relatively large body sizes independently of each other. Their common ancestor was a much smaller monkey but was otherwise reminiscent of the later descendant species. Apparently, nature selected for larger monkey bodies on both continents during the last 30 million years. Convergence , or convergent evolution, is the development of a similar anatomical feature in distinct species lines after divergence from a common ancestor that did not have the initial trait that led to it. The common ancestor is usually more distant in time than is the case with parallelism. The similar appearance and predatory behavior of North American wolves and Tasmanian wolves is an example. The former is a placental mammal and the latter is an Australian marsupial. Their common ancestor lived during the age of the dinosaurs more than 100 million years ago and was very different from these descendants today. There are, in fact, a number of other Australian marsupials that are striking examples of convergent evolution with placental mammals elsewhere.

Tasmanian wolf or tiger (now extinct)

Mexican wolf

Examples of Convergent Evolution--ant eating mammals from four continents This link takes you to an external website. To return here, you must click the "back" button on your browser program.

Both parallelism and convergence are thought to be due primarily to separate species lines experiencing the same kinds of natural selection pressures over long periods of time. Analogies are anatomical features that have the same form or function in different species that have no known common ancestor. For instance, the wings of a bird and a butterfly are analogous structures because they are superficially similar in shape and function. Both of these very distinct species lines solved the problem of getting off of the ground in essentially the same way. However, their wings are quite different on the inside. Bird wings have an internal framework consisting of bones, while butterfly wings do not have any bones at all and are kept rigid mostly through fluid pressure. Analogies may be due to homologies or homoplasies, but the common ancestor, if any, is unknown.

Problems in Classifying Organisms

Listing characteristics that distinguish one species from another has the effect of making it appear that the species and their distinctive attributes are fixed and eternal. We must always keep in mind that they were brought about by evolutionary processes that operated not merely at some time in the distant past, but which continue to operate in the present and can be expected to give rise to new forms in the future. Species are always changing. As a consequence, they are essentially only a somewhat arbitrarily defined point along an evolutionary line.

It is also important to realize that most species are physically and genetically diverse. Many are far more varied than humans. When you think of an animal, such as the jaguar shown here, and describe it in terms of its specific traits (fur color patterns, body shape, etc.), it is natural to generalize and to think of all jaguars that way. To do so, however, is to ignore the reality of diversity in nature.

Jaguar

Another problem in classifying a newly discovered organism is in determining the specific characteristics that actually distinguish it from all other types of organisms. There is always a lively debate among researchers over defining new species because it is not obvious what are the most important traits. There are two schools of thought in resolving this dilemma. The first defines new species based on minor differences between organisms. This is the splitter approach. The second tends to ignore minor differences and to emphasize major similarities. This lumper approach results in fewer species being defined. Ideally, this dispute could be settled by breeding experiments--if two organisms can mate and produce fertile offspring, they are probably members of the same species. However, we must be careful because members of very closely related species can sometimes produce offspring together, and a small fraction of those may be fertile. This is the case with mules, which are the product of mating between female horses and male donkeys. About one out of 10,000 mules is fertile. Does this mean that horses and donkeys are in the same species? Whatever the answer may be, it is clear that species are not absolutely distinct entities, though by naming them, we implicitly convey the idea that they are.
Tigons and Ligers--what happens when tigers and lions mate This link takes you to an external website. To return here, you must click the "back" button on your browser program.

Breeding experiments are rarely undertaken to determine species boundaries because of the practical difficulties. It is time consuming and wild animals do not always cooperate. Using this kind of reproductive data for defining species from the fossil record is impossible since we cannot go back in time to observe breeding patterns and results. Comparisons of DNA sequences are now becoming more commonly used as an aid in distinguishing species. If two animals share a great many DNA sequences, it is likely that they are at least closely related. Unfortunately, this usually does not conclusively tell us that they are members of the same species. Therefore, we are still left with morphological characteristics as the most commonly used criteria for identifying species differences. The Linnaean scheme for classification of living things lumps organisms together based on presumed homologies. The assumption is that the more homologies two organisms share, the closer they must be in terms of evolutionary distance. The higher, more

inclusive divisions of the Linnaean system are created by including together closely related clusters of the immediately lower divisions. The result is a hierarchical system of classification with the highest category consisting of all living things. The lowest category consists of a single species. Each of the categories above species can have numerous subcategories. In the example below, only two genera (plural of genus) are listed per family but there could be many more or only one.
order family genus species species genus species species genus species species family genus species species

Most researchers today take a cladistics approach to classification. This involves making a distinction between derived and primitive traits when evaluating the importance of homologies in determining placement of organisms within the Linnaean classification system. Derived traits are those that have changed from the ancestral form and/or function. An example is the foot of a modern horse. Its distant early mammal ancestor had five digits. The bones of these digits have been largely fused together in horses giving them essentially only one toe with a hoof. In contrast, primates have retained the primitive characteristic of having five digits on the ends of their hands and feet. Animals sharing a great many homologies that were recently derived, rather than only ancestral, are more likely to have a recent common ancestor. This assumption is the basis of cladistics.

Kingdom to Subphylum
The highest category in the Linnaean system of classification is the kingdom. At this level, organisms are distinguished on the basis of cellular organization and methods of nutrition. Whether they are single- or multiple-celled and whether they absorb, ingest, or produce food are critical factors. Based on these types of distinctions, the biological sciences, now usually define at least five kingdoms of living things: Kingdom Monera Protista Fungi Plantae Animalia (animals) (plants) Types of Organisms bacteria, blue-green algae, and spirochetes protozoans and algae of various types funguses, molds, mushrooms, yeasts, mildews, and smuts mosses, ferns, woody and non-woody flowering plants sponges, worms, insects, fish, amphibians, reptiles, birds, and mammals

NOTE: A growing number of researchers now divide the Monera into two distinct kingdoms: Eubacteria (the true bacteria) and Archaebacteria (bacteria-like organisms that live in extremely harsh anaerobic environments such as hot springs, deep ocean volcanic vents, sewage treatment plants, and swamp sediments). Viruses, prions, and other non-cellular organic entities are not included in the kingdoms of living things.

Most macroscopic creatures are either plants or animals. Of course, humans are animals. The distinction between the plant and animal kingdoms is based primarily on the sources of nutrition and the capability of locomotion or movement. Plants produce new cell matter out of inorganic material by photosynthesis. They do not have the ability to move around their environment except by growing or being transported by wind, water, or other external forces.

Kingdom Animalia Kingdom Plantae

In contrast, animals do not produce their own food but must eat other organisms to obtain it. Animals are generally more complex structurally. Unlike plants, they have nerves and muscles that aid in rapid, controlled movement around their environment. Animal cells usually do not have rigid walls like those of plants. This accounts for the fact that your skin and flesh are flexible and the trunk of a tree is not. This simple dichotomy between plants and animals is not adequate to encompass all life forms. Some organisms have characteristics which do not qualify them to fit neatly into either kingdom. For instance, funguses and most bacteria do not photosynthesize and most of them lack a means of controlled locomotion. Some organisms have attributes of both plants and animals. For instance, there is a group of common singlecell species living in fresh water ponds called Euglena that photosynthesize and have their own means of locomotion (whip-like tale structures called flagella). Because of these and other exceptions, new kingdoms of living things had to be created.
More information about the kingdoms of living things

Research done over the last half century has shown us that there are even stranger organisms that live in extremely harsh anaerobic environments such as hot springs, deep ocean volcanic vents, sewage treatment plants, and swamp sediments. Unlike other life forms, they usually get their energy from geological sources rather than from the sun. There are also microscopic things that are not quite alive by definition but have some characteristics that are similar to living things. These are the viruses and prions. It is easy to overlook the importance of these extremely small things because they cannot be seen with the naked eye. However, there are very likely around ten times as many viruses as all living things put together. There are about 50 million viruses in 1 cm3 of ocean water. It has been estimated that these viruses are responsible for the death of 20% of all oceanic bacteria every day, thereby keeping the phenomenal reproductive capability of bacteria under control. There are also complex interactions between bacteria, viruses, and other microbal life forms within our own bodies. Most of the time, there are about 10 times as many microbial cells within us as there are body cells.

Phylum
Immediately below kingdom is the phylum level of classification. At this level, animals are grouped together based on similarities in basic body plan or organization. For instance, species in the phylum Arthropoda have external skeletons as well as jointed bodies and limbs. Insects, spiders, centipedes, lobsters, and crabs are all arthropods.

Phylum Arthropoda

Phylum Mollusca

In contrast, members of the phylum Mollusca have soft, unsegmented bodies that are usually, but not always, enclosed in hard shells. They also usually have at least one strong foot that helps them move. Octopi, squids, cuttlefish, snails, slugs, clams, and other shellfish are mollusks.

There are at least 33 phyla (plural of phylum) of animals. Humans are members of the phylum Chordata . All of the chordates have elongated bilaterally symmetrical bodies. That is to say, the left and right sides are essentially mirror images of each other. If there are two functionally similar body parts, they are usually found roughly equidistant from the center line, parallel to each other. Note the location of the woman's eyes, nostrils, and cheeks relative to the center line of her body. At some time in their life cycle, chordates have a pair of lateral gill slits or pouches used to obtain oxygen in a liquid environment. In the case of humans, other mammals, birds, and reptiles, lungs replace rudimentary gill slits after the embryonic stage of development. Frogs replace them with lungs in the transition from tadpoles to adults. Fish retain their gill slits all of their lives.
Bilateral symmetry (phylum Chordata)

Gill slits (phylum Chordata)

Chordates also have a notochord at some phase in their life cycle. This is a rudimentary internal skeleton made of stiff cartilage that runs lengthwise under the dorsal surface of the body. Generally, there is a single hollow nerve chord on top of the notochord. Among humans and the other vertebrates, the notochord is replaced by a more complex skeleton following the embryonic stage of development. Members of the phylum Chordata also often have a head, a tail, and a digestive system with an opening at both ends of the body. In other words, the body organization is essentially that of a tube in which food enters one end and waste matter passes out of the other. The chordates include mammals, birds, reptiles, amphibians, fish, as well as the primitive lancelets (or amphioxus) and tunicates (or sea squirts).

Notochord in a lancelet (phylum Chordata)

Tunicate (phylum Chordata)

Subphylum
The chordates are divided into three subphyla. Humans are members of the subphylum Vertebrata . Among the vertebrates, the notochord is replaced by a more complex spinal chord late in the embryonic stage of development. A segmented vertebral (or spinal) column of cartilage and/or bone develops around the spinal chord of vertebrates to protect it from injury. At one end of the spinal chord is a head with a brain and paired sense organs that function together to coordinate movement and sensation. Vertebrata is the most advanced and numerous subphylum of chordates. It includes all of the fish, amphibians, reptiles, birds, and mammals. Collectively, there are about 43,000 living vertebrate species in comparison to just over 1500 species in the other two invertebrate subphyla of chordates.

Human skeleton

Class
The subphylum Vertebrata includes all of the familiar large animals and some rare and unusual ones as well. The 7 living classes of vertebrates are distinguished mostly on the basis of their skeletal system, general environmental adaptation, and reproductive system.
subphylum: class: Agnatha Chondrichthyes Vertebrata Osteichthyes Amphibia Reptilia Aves Mammalia

Three of the vertebrate classes are fish. The most primitive of these is Agnatha . It consists of jawless fish that do not have scales. These are the lampreys and hagfish. Fish that have skeletons consisting of hard rubber-like cartilage rather than bone are members of the class Chondrichthyes . These are the sharks and rays. All of the bony fish are members of the class Osteichthyes . Tuna, bass, salmon, and trout are examples of Osteichthyes.

Ray (class Chondrichthyes) and bony fish (class Osteichthyes)

Animals in the class Amphibia spend part of their lives under water and part on land. Frogs, toads, and salamanders are amphibians. Many of these species must keep their skin moist by periodically returning to wet areas. All of them must return to water in order to reproduce since their eggs would dry out otherwise. They start life with gills, like fish, and later develop lungs to breathe air.

Salamander and frog (class Amphibia)

The class Reptilia includes turtles, snakes, lizards, alligators, and other large reptiles. All of them have lungs to breathe on land and skin that does not need to be kept wet. They produce an amniote egg which usually has a leather hard shell that protects the embryo from drying out. This is an advantage over fish and amphibians because the amniote egg can be laid on land where it is usually safer from predators than it would be in lakes, rivers, and oceans.

Tortoise, snake, and lizard (class Reptilia)

The class Aves includes all the birds. They also produce amniote eggs but usually give them greater protection from predators by laying them high off of the ground or in other relatively inaccessible locations. In the case of both reptiles and birds, the eggs are fertilized within the reproductive tract of females.

Birds (class Aves)

Dogs, cats, bears, humans and most other large animals today are members of the vertebrate class Mammalia . All mammals conceive their young within the reproductive tract of the mother and, after birth, nourish them with milk produced by their mammary glands . Mammals are heterodonts with strong jaws. That is to say, they have a variety of specialized teeth (incisors, canines, premolars, and molars). This allows them to chew their food into small pieces. Many reptiles must swallow their prey whole, which limits them to hunting smaller animals.

Mammalian heterodontism

Like birds, mammals are endothermic , or warm blooded. They are able to maintain a relatively constant body temperature regardless of external environmental conditions mainly by using internal physiological mechanisms. In other words, they are homeothermic, or stable in core body temperature, as a result of endothermy. All other classes of living animals are ectothermic , or cold blooded. They keep their body temperature in a normal range mainly by avoiding exposure to environmental temperature extremes. On hot days, reptiles usually remain in shaded areas to prevent fatal overheating. On cold nights, their lowered body temperature can cause them to become sluggish and inactive. In contrast, endothermic animals are able to remain active at night and often in the winter when the air temperatures are especially cold. They can also move about in the heat of very warm days. This ability most likely provided an advantage for the early small mammals in surviving alongside dinosaurs and other large reptiles. The downside of endothermy is the need to consume far more calories relative to body size in order to maintain a constant core body temperature. Small mammals, such as moles with their rapid metabolism rates, must eat insects or

other high calorie foods every half hour or so in order to stay alive. By comparison, cold blooded rattlesnakes have been known to go without food for as long as two years. Aiding in mammal body temperature control is their insulating hair and sweat glands. The latter function to dissipate heat by evaporative cooling. Compared to most other land mammals, humans are relatively hairless, but they have far more sweat glands. Mammals have four chambered hearts (like birds), complex nervous systems, and large brains. This broad range of useful features has made mammals highly adaptive and successful. They first appeared about 200,000,000 years ago in the age of dinosaurs and replaced reptiles as the dominant class of land animals after 65,000,000 years ago. Important to mammalian success is their reproductive system. Their bodies took the amniote egg revolution of reptiles one step further. In effect, the uterus functions as the protective eggshell. Young mammals spend a long period of their early development within their mother's uterus. After birth, they are provided with protein and fat rich milk to eat and are usually protected until maturity. Pregnancy and milk production require mothers to significantly increase their calorie consumption in order to provide nutrients for their infants. A nursing human female normally uses about 30% of her body's energy just to produce milk.

Mammalian mother and her baby

Despite their success, mammals still only make up about .4% of known animal species. It is humbling to realize that all chordates together are only just over 3.7% of known animal species. By comparison, well over 1/2 of all animal species are insects.

Subclass to Infraclass
Among the mammals, there are three major variations in reproductive systems. This is the basis for dividing them into subclasses and infraclasses.
class: subclass: Prototheria infraclass: Mammalia Theria Metatheria Eutheria

Members of the subclass Prototheria lay eggs like most non-mammalian vertebrates. However, they feed their newborn with mammary gland secretions like all other mammals. They lack nipples, but the skin over their mammary glands exude milk for their babies. The Prototheria are also referred to as monotremes , which literally means that they have one opening for excretion and reproduction. This is similar to birds. There are only three surviving rare species groups of Prototheria. These are the Australian platypus and 2 echidna (spiny anteater) species of Australia and New Guinea.

Platypus (subclass Prototheria)

Echidna (subclass Prototheria)

Genome of the Platypus--video clip from Nature.com (length = 7 mins. 30 secs.)

All other living mammalian species, including humans, are in the subclass Theria . They have in common the fact that they give birth to live young. Therian mammals apparently did not evolve from the Prototheria. The relatively primitive prototherian reproductive system evidently evolved after their evolutionary line separated from the other early mammals. The oldest infraclass of therian mammals is the Metatheria , or the marsupials . Their young are born very immature and cannot live without further development in the mother's pouch. The word marsupial comes from marsupium, the Latin word for purse. Marsupials include kangaroos, koalas, opossums, and many other similar animals. Most of them are native only to Australia and New Guinea.

Kangaroo and koala (infraclass Metatheria)

Most mammal species, including humans, are in the infraclass Eutheria . They are also referred to as placental mammals. Eutherian mothers carry their unborn children within the uterus where they are nourished and protected until an advanced stage is reached. This is made possible by the umbilical cord and placenta which connects the fetus to the uterus wall and enables nutrients and oxygen to get to the offspring as well as provides a means of eliminating waste. Placental mammals have been extremely successful in outcompeting monotremes and marsupials for ecological niches. This is mostly due to the fact that their babies are born more mature, which increases their chances of survival. Marsupials give birth to early stage fetuses. Placental mammals give birth after fetuses are much more developed. The downside is that pregnant placental mammals must consume significantly more calories to nurture their fetuses and themselves, especially during the second half of their pregnancies. Placental mammals are found on all continents, in the air, and in the seas. Primates, cats, dogs, bears, hoofed animals, rodents, bats, seals, dolphins, and whales are among the dominant placental mammal groups today. Nearly 94% of all mammal species now are placental mammals.
Human fetus in utero

Whale, dolphin, monkey, and zebra (infraclass Eutheria)

The next tutorial in this series, The Primates, investigates all of the Linnaean classification categories below the infraclass level for humans, apes, monkeys, and some other closely related animals. This will take us from the "order" level down to "species."

NEWS: A team of researchers led by Wesley Warren at Washington University School of Medicine reported their completion of a draft of the platypus genome sequence in the May 8, 2008 issue of the journal Nature. This showed that the platypus has about 18,500 genes (about 2/3 as many as humans) and that 82% are shared with humans, mice, dogs, opossums, and chickens. Other platypus genes show links to reptiles, including those related to egg-laying, vision, and venom production. Adult male

platypuses can inject their poison with a spur just above the heel of each hind foot. Apparently, they use this as a weapon against other males during the mating season. Platypuses are also unusual in having sensors in their bills that are used to detect faint electrical fields from their prey when they hunt them under water. NEWS: The results of a 5 year global project sponsored by the Union for Conservation of Nature to survey all living mammals has been completed. The researchers concluded in October 2008 that one half of the 5487 mammal species are declining in numbers and at least 1/4 are now threatened with extinction due primarily to habitat destruction, hunting by humans, and climate change (Jan Schipper et al., Science 1165115, 2008).
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Mendel's Genetics
For thousands of years farmers and herders have been selectively breeding their plants and animals to produce more useful hybrids . It was somewhat of a hit or miss process since the actual mechanisms governing inheritance were unknown. Knowledge of these genetic mechanisms finally came as a result of careful laboratory breeding experiments carried out over the last century and a half.

Hybridized domesticated horses

By the 1890's, the invention of better microscopes allowed biologists to discover the basic facts of cell division and sexual reproduction. The focus of genetics research then shifted to understanding what really happens in the transmission of hereditary traits from parents to children. A number of hypotheses were suggested to explain heredity, but Gregor Mendel , a little known Central European monk, was the only one who got it more or less right. His ideas had been published in 1866 but largely went unrecognized until 1900, which was long after his death. His early adult life was spent in relative obscurity doing basic genetics research and Gregor Mendel teaching high school mathematics, physics, and Greek in Brno (now 1822-1884 in the Czech Republic). In his later years, he became the abbot of his monastery and put aside his scientific work.

Common edible peas While Mendel's research was with plants, the basic underlying principles of heredity that he discovered also apply to people and other animals because the mechanisms of heredity are essentially the same for all complex life forms.

Through the selective cross-breeding of common pea plants (Pisum sativum) over many generations, Mendel discovered that certain traits show up in offspring without any blending of parent characteristics. For instance, the pea flowers are either purple or white--intermediate colors do not appear in the offspring of cross-pollinated pea plants. Mendel observed seven traits that are easily recognized and apparently only occur in one of two forms: 1. 2. 3. 4. flower color is purple or white flower position is axil or terminal stem length is long or short seed shape is round or wrinkled 5. seed color is yellow or green 6. pod shape is inflated or constricted 7. pod color is yellow or green

This observation that these traits do not show up in offspring plants with intermediate forms was critically important because the leading theory in biology at the time was that inherited traits blend from generation to generation. Most of the leading scientists in the 19th century accepted this "blending theory." Charles Darwin proposed another equally wrong theory known as "pangenesis" . This held that hereditary "particles" in our bodies are affected by the things we do during our lifetime. These modified particles were thought to migrate via blood to the reproductive cells and subsequently could be inherited by the next generation. This was essentially a variation of Lamarck's incorrect idea of the "inheritance of acquired characteristics." Mendel picked common garden pea plants for the focus of his research because they can be grown easily in large numbers and their reproduction can be manipulated. Pea plants have both male and female reproductive organs. As a result, they can either selfpollinate themselves or cross-pollinate with another plant. In his experiments, Mendel was able to selectively cross-pollinate purebred plants with particular traits and observe the outcome over many generations. This was the basis for his conclusions about the nature of genetic inheritance.

Reproductive structures of flowers

In cross-pollinating plants that either produce yellow or green pea seeds exclusively, Mendel found that the first offspring generation (f1) always has yellow seeds. However, the following generation (f2) consistently has a 3:1 ratio of yellow to green.

This 3:1 ratio occurs in later generations as well. Mendel realized that this was the key to understanding the basic mechanisms of inheritance.

He came to three important conclusions from these experimental results: 1. that the inheritance of each trait is determined by "units" or "factors" that are passed on to descendents unchanged (these units are now called genes ) 2. that an individual inherits one such unit from each parent for each trait 3. that a trait may not show up in an individual but can still be passed on to the next generation. It is important to realize that, in this experiment, the starting parent plants were homozygous for pea seed color. That is to say, they each had two identical forms (or alleles ) of the gene for this trait--2 yellows or 2 greens. The plants in the f1 generation were all heterozygous . In other words, they each had inherited two different alleles--one from each parent plant. It becomes clearer when we look at the actual genetic makeup, or genotype , of the pea plants instead of only the phenotype , or observable physical characteristics.

Note that each of the f1 generation plants (shown above) inherited a Y allele from one parent and a G allele from the other. When the f1 plants breed, each has an equal chance of passing on either Y or G alleles to each offspring. With all of the seven pea plant traits that Mendel examined, one form appeared dominant over the other, which is to say it masked the presence of the other allele. For example, when the genotype for pea seed color is YG (heterozygous), the phenotype is yellow. However, the dominant yellow allele does not alter the recessive green one in any way. Both alleles can be passed on to the next generation unchanged. Mendel's observations from these experiments can be summarized in two principles: 1. the principle of segregation 2. the principle of independent assortment According to the principle of segregation, for any particular trait, the pair of alleles of each parent separate and only one allele passes from each parent on to an offspring. Which allele in a parent's pair of alleles is inherited is a matter of chance. We now know that this segregation of alleles occurs during the process of sex cell formation (i.e., meiosis ).

Segregation of alleles in the production of sex cells

According to the principle of independent assortment, different pairs of alleles are passed to offspring independently of each other. The result is that new combinations of genes present in neither parent are possible. For example, a pea plant's inheritance of the ability to produce purple flowers instead of white ones does not make it more likely that it will also inherit the ability to produce yellow pea seeds in contrast to green ones. Likewise, the principle of independent assortment explains why the human inheritance of a particular eye color does not increase or decrease the likelihood of having 6 fingers on each hand. Today, we know this is due to the fact that the genes for independently assorted traits are located on different chromosomes . These two principles of inheritance, along with the understanding of unit inheritance and dominance, were the beginnings of our modern science of genetics. However, Mendel did not realize that there are exceptions to these rules. Some of these exceptions will be explored in the third section of this tutorial and in the Synthetic Theory of Evolution tutorial. By focusing on Mendel as the father of genetics, modern biology often forgets that his experimental results also disproved Lamarck's theory of the inheritance of acquired characteristics described in the Early Theories of Evolution tutorial. Mendel rarely gets credit for this because his work remained essentially unknown until long after Lamarck's ideas were widely rejected as being improbable.

NOTE: Some biologists refer to Mendel's "principles" as "laws". NOTE: One of the reasons that Mendel carried out his breeding experiments with pea plants was that he could observe inheritance patterns in up to two generations a year. Geneticists today usually carry out their breeding experiments with species that reproduce much more rapidly so that the amount of time and money required is significantly reduced. Fruit flies and bacteria are commonly used for this purpose now. Fruit flies reproduce in about 2 weeks from birth, while bacteria, such as E. coli found in our digestive systems, reproduce in only 3-5 hours.

Probability of Inheritance
The value of studying genetics is in understanding how we can predict the likelihood of inheriting particular traits. This can help plant and animal breeders in developing varieties that have more desirable qualities. It can also help people explain and predict patterns of inheritance in family lines. One of the easiest ways to calculate the mathematical probability of inheriting a specific trait was invented by an early 20th century English geneticist named Reginald Punnett . His technique employs what we now call a Punnett square. This is a simple

graphical way of discovering all of the potential combinations of genotypes that can occur in children, given the genotypes of their parents. It also shows us the odds of each of the offspring genotypes occurring. Setting up and using a Punnett square is quite simple once you understand how it works. You begin by drawing a grid of perpendicular lines:

Next, you put the genotype of one parent across the top and that of the other parent down the left side. For example, if parent pea plant genotypes were YY and GG respectively, the setup would be:

Note that only one letter goes in each box for the parents. It does not matter which parent is on the side or the top of the Punnett square. Next, all you have to do is fill in the boxes by copying the row and column-head letters across or down into the empty squares. This gives us the predicted frequency of all of the potential genotypes among the offspring each time reproduction occurs.

In this example, 100% of the offspring will likely be heterozygous (YG). Since the Y (yellow) allele is dominant over the G (green) allele for pea plants, 100% of the YG

offspring will have a yellow phenotype, as Mendel observed in his breeding experiments. In another example (shown below), if the parent plants both have heterozygous (YG) genotypes, there will be 25% YY, 50% YG, and 25% GG offspring on average. These percentages are determined based on the fact that each of the 4 offspring boxes in a Punnett square is 25% (1 out of 4). As to phenotypes, 75% will be Y and only 25% will be G. These will be the odds every time a new offspring is conceived by parents with YG genotypes.

An offspring's genotype is the result of the combination of genes in the sex cells or gametes (sperm and ova) that came together in its conception. One sex cell came from each parent. Sex cells normally only have one copy of the gene for each trait (e.g., one copy of the Y or G form of the gene in the example above). Each of the two Punnett square boxes in which the parent genes for a trait are placed (across the top or on the left side) actually represents one of the two possible genotypes for a parent sex cell. Which of the two parental copies of a gene is inherited depends on which sex cell is inherited--it is a matter of chance. By placing each of the two copies in its own box has the effect of giving it a 50% chance of being inherited. If you are not yet clear about how to make a Punnett Square and interpret its result, take the time to try to figure it out before going on.

Are Punnett Squares Just Academic Games?

Why is it important for you to know about Punnett squares? The answer is that they can be used as predictive tools when considering having children. Let us assume, for instance, that both you and your mate are carriers for a particularly unpleasant genetically inherited disease such as cystic fibrosis . Of course, you are worried about whether your children will be healthy and normal. For this example, let us define "A" as being the dominant normal allele and "a" as the recessive abnormal one that is responsible for cystic fibrosis. As carriers, you and your mate are both heterozygous (Aa). This disease only afflicts those who are homozygous recessive (aa). The Punnett square below makes it clear that at each birth, there will be a 25% chance of you having a normal homozygous (AA) child, a 50% chance of a healthy heterozygous (Aa) carrier child like you and your mate, and a 25% chance of a homozygous recessive (aa) child who probably will eventually die from this condition.

If both parents are carriers of the recessive allele for a disorder, all of their children will face the following odds of inheriting it: 25% chance of having the recessive disorder 50% chance of being a healthy carrier 25% chance of being healthy and not have the recessive allele at all

If a carrier (Aa) for such a recessive disease mates with someone who has it (aa), the likelihood of their children also inheriting the condition is far greater (as shown below). On average, half of the children will be heterozygous (Aa) and, therefore, carriers. The remaining half will inherit 2 recessive alleles (aa) and develop the disease.

If one parent is a carrier and the other has a recessive disorder, their children will have the following odds of inheriting it: 50% chance of being a healthy carrier 50% chance having the recessive disorder

It is likely that every one of us is a carrier for a large number of recessive alleles. Some of these alleles can cause life-threatening defects if they are inherited from both parents. In addition to cystic fibrosis, albinism, and beta-thalassemia are recessive disorders. Some disorders are caused by dominant alleles for genes. Inheriting just one copy of such a dominant allele will cause the disorder. This is the case with Huntington disease, achondroplastic dwarfism, and polydactyly. People who are heterozygous (Aa) are not healthy carriers. They have the disorder just like homozygous dominant (AA) individuals.

If only one parent has a single copy of a dominant allele for a dominant disorder, their children will have a 50% chance of inheriting the disorder and 50% chance of being entirely normal.

Punnett squares are standard tools used by genetic counselors. Theoretically, the likelihood of inheriting many traits, including useful ones, can be predicted using them. It is also possible to construct squares for more than one trait at a time. However, some traits are not inherited with the simple mathematical probability suggested here. We will explore some of these exceptions in the next section of the tutorial.

Exceptions to Simple Inheritance

Since Mendel's time, our knowledge of the mechanisms of genetic inheritance has grown immensely. For instance, it is now understood that inheriting one allele can, at times, increase the chance of inheriting another or can affect how and when a trait is expressed in an individual's phenotype. Likewise, there are degrees of dominance and recessiveness with some traits. The simple rules of Mendelian inheritance do not apply in these and other exceptions. They are said to have non-Mendelian inheritance patterns.

Polygenic Traits
Some traits are determined by the combined effect of more than one pair of genes. These are referred to as polygenic , or continuous, traits. An example of this is human stature. The combined size of all of the body parts from head to foot determines the height of an individual. There is an additive effect. The sizes of all of these body parts are, in turn, determined by numerous genes. Human skin, hair, and eye color are also polygenic traits because they are influenced by more than one allele at different loci. The result is the perception of continuous gradation in the expression of these traits.

Polygenic traits: stature, body shape, hair and skin color

NOTE: whether an individual achieves his or her genetically programmed height is significantly affected by human growth hormones (HGH) produced in the pituitary gland. A deficiency in the amount of these hormones during childhood and puberty can result in stunted growth. Too much of them can cause excessive growth resulting in exceptional height. Differences in diet and other environmental factors during the crucial growth years can also be important in determining stature and other complex traits. Usually, about 10% of an individual's height is due to the environment.

Intermediate Expression
Apparent blending can occur in the phenotype when there is incomplete dominance resulting in an intermediate expression of a trait in heterozygous individuals. For instance, in primroses, snapdragons, and four-o'clocks, red or white flowers are homozygous while pink ones are heterozygous. The pink flowers result because the

single "red" allele is unable to code for the production of enough red pigment to make the petals dark red.

Another example of an intermediate expression may be the pitch of human male voices. The lowest and highest pitches apparently are found in men who are homozygous for this trait (AA and aa), while the intermediate range baritones are heterozygous (Aa). The child-killer disease known as Tay-Sachs is also characterized by incomplete dominance. Heterozygous individuals are genetically programmed to produce only 40-60% of the normal amount of an enzyme that prevents the disease. Fortunately for Mendel, the pea plant traits that he studied were controlled by genes that do not exhibit an intermediate expression in the phenotype. Otherwise, he probably would not have discovered the basic rules of genetic inheritance.

Codominance
For some traits, two alleles can be codominant. That is to say, both are expressed in heterozygous individuals. An example of this is people who have an AB blood type for the ABO blood system. When they are tested, these individuals actually have the characteristics of both type A and type B blood. Their phenotype is not intermediate between the two.

Type AB blood testing as both A and B

Multiple-allele Series
The ABO blood type system is also an example of a trait that is controlled by more than just a single pair of alleles. In other words, it is due to a multiple-allele series. In this

case, there are three alleles (A, B, and O), but each individual only inherits two of them (one from each parent). Some traits are controlled by far more alleles. For instance, the human HLA system, which is responsible for identifying and rejecting foreign tissue in our bodies, can have at least 30,000,000 different genotypes. It is the HLA system which causes the rejection of organ transplants. The more we learn about human genetics the more it becomes clear that multiple-allele series are very common. In fact, it now appears that they are more common than simple two allele ones.

Modifying and Regulator Genes

There are two classes of genes that can have an effect on how other genes function. They are called modifying genes and regulator genes. Modifying genes alter how certain other genes are expressed in the phenotype. For instance, there is a dominant cataract gene which will produce varying degrees of vision impairment depending on the presence of a specific allele for a companion modifying gene. However, cataracts also can be promoted by diabetes and common environmental factors such as excessive ultraviolet radiation, and alcoholism. Nearly half of all people in North America over 65 years of age eventually develop them.

Regulator genes can either initiate or block the expression of other genes. They control the production of a variety of chemicals in plants and animals. For instance, the time of production of specific proteins that will be new structural parts of our bodies can be controlled by such regulator genes. Shortly after conception, regulator genes work as master switches orchestrating the timely development of our body parts. They are also responsible for changes that occur in our bodies as we grow older. In other words, they control the maturation and aging processes. Regulator genes that are involved in subdividing an embryo into what will become the major body parts of an individual are also referred to as homeotic , homeobox , or Hox genes. They are responsible for setting generalized cells on the path to become a head, torso, arms, legs, etc.
Gene Control--video clip from Teachers' Domain Can We Slow Aging--video clip from Nova ScienceNow

View in: QuickTime or Windows Media Player (length = 2 mins 58 secs)

about a regulator gene that controls the aging process (length = 11 mins 30 secs)

Incomplete Penetrance
Some genes are incompletely penetrant. That is to say, their effect does not normally occur unless certain environmental factors are present. For example, you may inherit the genes that are responsible for type 2 diabetes but never get the disease unless you become greatly overweight, persistently stressed psychologically, or do not get enough sleep on a regular basis. Similarly, the genes that cause the chronic autoimmune disease, multiple sclerosis , may be triggered by the Epstein-Barr virus and possibly other specific environmental stresses. New research suggests that abundant exposure to the sun in childhood can provide some protection from developing MS. Subsequently, people who grow up in tropical and subtropical regions of the world have significantly lower rates of MS as adults.

Sex Related Genetic effects

There are three categories of genes that may have different effects depending on an individual's gender. These are referred to as: 1. sex-limited genes 2. sex-controlled genes

Human gender differences in facial hair

3. genome imprinting Sex-limited genes are ones that are inherited by both men and women but are normally only expressed in the phenotype of one of them. The heavy male beard is an example. While women have facial hair it is most often very fine and comparatively sparse.

In contrast, sex-controlled genes are expressed in both sexes but differently. An example of this is gout , a disease that causes painfully inflamed joints. If the gene is present, men are nearly eight times more likely than women to have severe symptoms. Some genes are known to have a different effect depending on the gender of the parent from whom they are inherited. This phenomenon is referred to as genome imprinting or genetic imprinting. Apparently, diabetes , psoriasis , and some rare genetically inherited diseases, such as a form of mental retardation known as Angelman syndrome , can follow this inheritance pattern. Recent research by Catherine Dulac of Harvard University points to genetic imprinting as being an important factor in causing male and female brains to develop somewhat differently. She suggests that this is due to the fact that some of the genes inherited from the opposite sex parent are likely to be turned off following conception.

Pleiotropy
A single gene may be responsible for a variety of traits. This is called pleiotropy . The complex of symptoms that are collectively referred to as sickle-cell trait , or sickle-cell anemia, is an example. A single gene results in irregularly shaped red blood cells that painfully block blood vessels, cause poor overall physical development, as well as related heart, lung, kidney, and eye problems. Another pleiotropic trait is albinism . The gene for this trait not only results in a deficiency of skin, hair, and eye pigmentation but also causes defects in vision.

Stuttering Alleles
Lastly, it is now known that some genetically inherited diseases have more severe symptoms each succeeding generation due to segments of the defective genes being doubled in their transmission to children (as illustrated below). These are referred to as stuttering alleles or unstable alleles. Examples of this phenomenon are Huntington's disease, fragile-X syndrome, and the myotonic form of muscular dystrophy .

Unstable allele doubling each generation

Mendel believed that all units of inheritance are passed on to offspring unchanged. Unstable alleles are an important exception to this rule.

Environmental Influences
The phenotype of an individual is not only the result of inheriting a particular set of parental genes. The specific environmental characteristics of the uterus in which a fertilized egg is implanted and the health of the mother can have major impacts on the phenotype of the future child. For instance, oxygen deprivation or inappropriate hormone levels can cause lifelong, devastating effects. Likewise, accidents, poor nutrition, and other environmental influences throughout life can alter an individual's phenotype. Geneticists study identical or monozygotic twins to determine which traits are inherited and which ones were acquired following conception. Since monozygotic twins come from the same zygote, they are essentially identical in their genetic makeup. If there are any differences in their phenotypes, the environment is virtually always responsible. Such differences show up in basic capabilities such as handedness, which had been assumed to be entirely genetically determined. In rare instances, one monozygotic twin will be clearly right-handed while the other will be left-handed. This suggests that there may be both genetic and environmental influences in the development of this trait.

Summary
Researchers have identified more than 5,000 genetically inherited human diseases and abnormalities. As we learn more about the inheritance patterns for these traits, it is becoming clear that at least some of the twelve exceptions to the simple Mendelian rules of inheritance described here are, in fact, relatively common. It would not be surprising if other "exceptions" were discovered in the future. However, it is important to keep in mind that there are at least 18,000 human traits controlled by genes that follow the basic Mendelian rules of inheritance.

NEWS: Susan Lolle et al. reported in the March 2005 issue of Nature that they have discovered a plant species that can overwrite the genetic makeup inherited from parents. These cress plants seem to be able to revert back to the DNA sequences of their grandparents including genetic information that was lost in the intervening generation. The researchers suggest that since the DNA sequences were not present in the parents that there may be a "template-directed process that makes use of an ancestral RNA-sequence cache." The implication is that this is a form of inheritance that does not follow the basic tenets of classical genetics. ("Genome-wide Non-

Mendelian Inheritance of Extra-genomic Information in Arabidopsis", Nature, Vol. 434, No 7032, March 24, 2005)
-----------------------------------------------------------------------------------------------------------------------------------------http://www.allaboutscience.org/origin-of-life.htm Origin of Life - Spontaneous Generation For millennia, the Origin of Life was thought to be the result of Abiogenesis (also known as "Spontaneous Generation"). The doctrine of Spontaneous Generation holds that organic life could and does arise from inorganic matter. As late as the 17th century, there were recipes to "create" life. Take sweaty rags, wrap them around wheat, and set them in an open jar. In 21 days, you'll "create" mice. For rats, just throw garbage in the street. In a few days, rats will take the place of the garbage. All over the world, in Europe, Asia, Africa and the Americas, mankind was formulating recipes for "creating" bees, lice, scorpions, maggots, worms, frogs, etc. In 1668, Francesco Redi publicly opposed the idea of Spontaneous Generation. While it was generally accepted that rotting meat generated maggots, Redi disagreed. He maintained that maggots hatched from eggs laid by flies. To test his hypothesis, Redi performed one of the first known experiments to utilize a "control group." Thus began both the death of Spontaneous Generation and the birth of the modern era of scientific development. Redi placed meat in three flasks - one open, one sealed and one covered with gauze. Maggots appeared in the open flask, as the flies were able to reach the meat. Maggots did not appear in the sealed flask or the flask covered by gauze. At the time, this experiment was not thought to disprove Spontaneous Generation. It merely proved that maggots did not come from meat. Origin of Life - Louis Pasteur Spontaneous Generation was thought to be the Origin of Life until the late 1850's. It wasn't until Frenchman Louis Pasteur that this fallacy was finally disproved. In 1859, the French Academy of Science sponsored a Science Fair, the goal being to prove or disprove Spontaneous Generation. Young Pasteur's award winning experiment was a clever variation of earlier experiments performed by John Needham (1713-1781) and Lazzaro Spallanzani (17291799). Pasteur filled a long necked flask with meat broth. He then heated the glass neck and bent it into an "S" shape. Air could reach the broth, but gravity acted to trap airborne microorganisms in the curve of the neck. He then boiled the broth. After a time, no microorganisms had formed in the broth. When the flask was tipped so that the broth reached the microorganisms trapped in the neck, the broth quickly became cloudy with microscopic life. Thus, Pasteur disproved Spontaneous Generation. Furthermore, Pasteur proved that some microorganisms are airborne. Origin of Life - Origin of Species and Modern Day Science Class Spontaneous Generation was disproved as the Origin of Life in 1859. Ironically, it was this same year that Charles Darwin's Origin of Species was published. From this work arose the modern evolutionary movement, which is now thought to have occurred in six phases: (1) Cosmic Evolution (the origin of space, time, matter and energy from nothing); (2) Chemical Evolution (the development of the higher elements from hydrogen); (3) Stellar and Planetary Evolution (the origin of stars and planets); (4) Organic Evolution (the origin of organic life from a rock); (5) Macro Evolution (the origin of major kinds); and (6) Micro Evolution (the variation within the kinds). Only the sixth phase has been observed and documented. The first five are merely assumed. Interestingly, the fourth assumption is the old doctrine of Spontaneous Generation - organic life developing from inorganic matter (a rock). The sadly comical result is that some modern day textbooks devote a chapter to the work of Francesco Redi and Louis Pasteur, and their success in disproving Spontaneous Generation. Then, a few chapters later, school kids are taught that Spontaneous Generation is the Origin of Life.

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