Genetic variation

“ Even where the mutational variation appears to be one of gain, as happens when a positive character appears de novo in the phenotype, or when a dilute parental character is intensified in the offspring, it is, nevertheless, interpretable as a result of germinal loss, the loss, namely, total or partial, of a genetic inhibitor. Such inhibitive genes or factors are known to exist. ”

“ A few general theories from quantitative genetics form the basis of these genetic mechanisms (Falconer 1981) . First, an animal's phenotype is the result of its genotype and the environment in which it developed. ”

“ If synonymous sites harbor highly deleterious variants under strong purifying selection, then that must change our view of the functional importance of synonymous sites and their potential role in genetic disease, as a possible source for adaptation, and as the neutral foil in tests for selection. ”

“ It is demonstrated that among the fluctuating variations there are individuals which are able to transmit their particular variation and give rise by selection to a race, while the majority are not able to hand on their particular conditions to their progeny. Races developed by selection from such variations have not been carried beyond the normal limit of variability of the species. ”

“ The uniformity of the limits of variation within a species may be the result of similarly mutating genes, or of genes derived from hybridization with some exotic influence. Such hereditary property may become fairly well distributed in the course of time thruout any interbreeding population, and if the genes belong to groups of multiple factors controlling single characters in the organism, we have an explanation for the occurrence of every degree of variation between definite limits within a population. ”

“ No two individuals are exactly alike, and thus such continuous variations are universal. According to the theory of natural selection the course of evolutionary change in any organ or character would form a similar continuous series, the mean of each generation differing only by a small difference from that of the preceding. According to the modern mutationists such small differences are to be called fluctuations, and have no effect on evolution at all, are not even hereditary, are not due to genetic factors in the gametes. ”

“ Genetics, the study of heredity, can not successfully proceed by direct observation in the human species as it does with plants and rapidly-breeding animals, because the generations are too long. Less than three generations are of little value for genetic researches, and even three can rarely be observed to advantage by any one person. ”

“ It is here suggested that the modification as such, is not inherited, but is the condition under which congenital variations are favored and given time to get a hold on the organism, and are thus enabled by degrees to reach the fully adaptive level. When we remember that plastic modification and germinal variation have been working together all along the line of organic evolution, to reach the common goal of adaptation, it is difficult to believe that they have been all along wholly independent of each other. ”

“ These mutational forms are of several distinct and recognizable types which recur, and several of them breed true from their first appearance. The obvious difficulty, which in my judgment should make us unwilling at present to accept these occurrences as proof of the genesis of new species by mutation, is that we have as yet no certainty that the appearance of the new forms is not an effect of the recombination [Pg 102] of factors, such as is to be seen in so many generations of plants derived from a cross involving many genetic elements. The first question is what is Oenothera Lamarckiana? ”

“ The similar physiology and genome structure between the mouse and human facilitate ortholog comparison and functional identification between the two species. To determine if differences exist between essential and non-essential disease genes we examined several parameters in our analyses, including the physiological systems affected by each disease gene, the connectivity of each gene in protein-protein interaction networks, and the genetic mechanisms by which genes cause human disease. ”

“ It must, however, be remembered that, if the theory of genetic descent with accumulation of minute modifications be the true explanation of the production of new forms, it necessarily follows, that could a complete record be forthcoming of the ancestry of any actual species, there would be found in that pedigree no distinction of species or genera, for no sharply marked lines of limitation would be discoverable. ”

“ The transmissability of acquired characters has been called in question and is totally denied by a great number of leading biologists at the present day.
Darwin took Variation and Heredity as his basis and upon these two pillars he built up his theory of the origin of species and the evolution of organic forms. Biologists are now pushing their enquiries further back; they are not content to take Variation and Heredity as facts which require no further explanation. ”

“ Recognition of the distinction between dominant and recessive characters has, it must be conceded, created a very serious obstacle in the way of any rational and concrete theory of evolution. While variations of all kinds could be regarded as manifestations of some mysterious instability of organisms this difficulty did not occur to the mind of evolutionists. To most of those who have taken part in genetic analysis it has become a permanent and continual obsession. ”

“ Weismann. According to his conception, variations of germinal origin occur from time to time. By its innate plasticity the several parts of an organism implicated by their association with the varying part are modified in individual life in such away that their modifications cooperate with the germinal variation in producing an adaption of double origin, partly congenital, partly acquired. The organism then waits, so to speak, for a further congenital variation, when a like process of adaptation again occurs ”

“ It is however becoming probable that if more knowledge of the chemical and physical structure of organisms is to be attained, the clue will be found through Genetics, and thus that even in the uncoordinated accumulation of facts of Variation we are providing the means of analysis applicable not only to them, but to the problems of normality also.
The only classification that we can yet institute with any confidence among the phenomena of Variation is that which distinguishes on the one hand variations in the processes of division from variations in the nature of the substances divided. ”

“ For example, those with most black pigment and those with least black taken from a population continuously varying in this respect, were separately bred; but almost always the selection led to no sensible change in the position of the mean of the [Pg 221] population. The variations in these cases were evidently fluctuational. In some instances, however, real genetic differences were met with, and strains exhibiting them were, as usual, rapidly fixed.
Tower points out that several of the varieties (or species, as he prefers to call them) were obviously recessive to decemlineata. ”

“ Given that the genetic basis of human disease is often unknown, this method provides a means for identifying candidate genes, pathway members, and disease models by computationally identifying similar phenotypes within and across species. ”

“ The present is always found to be the key to the past. It is only by employing a similar method that biologists can hope to attack successfully the problems of Variation and Heredity. By actual observation and experiment they must seek to determine how species are being modified around us to-day and find out what characters are transmissible. The nature and causes of Variation and of Heredity will thus in time come to be understood.
It is only within recent years that any attempt has been made to study variations systematically. ”

“ Human Social Genomics
Initial indications that social environments might significantly affect the functional activity of the human genome came from studies dissecting leukocyte gene expression profiles into genetic and environmental components [8] , [9] . Gibson and colleagues found that ∼5% of genes expressed in leukocytes showed appreciable genetic regulation (e.g., via expression quantitative trait loci) , whereas >50% showed significant differences in expression across pastoral, rural, and urban social environments [9] . ”

“ The other possible explanation of these common limits of variability is that similar genes may have not only the same potentialities but the same lack of potentialities, reaching similar limits to their capacities for directing the growth of the individual organism or to withstand the effects of environmental factors. As Bateson put it, the degree of variation of an organism may be inherited as much as its degree of uniformity. ”

“ Of course if a dominant character is advantageous in itself, it will have a better chance of spreading through the race, than will an advantageous recessive character, because every hybrid that carries one dominant gene shows also the character, which increases the chance that it will propagate and spread the genes. ”

“ In a single period, in a limited area, there must have existed a population from which all of the present-day species, with their varying grades of relationships, have developed. This history of the expansion of a single genetic stock into 93 distinct populations, by processes of mutation, isolation, and on occasion subsequent recombination into hybrid populations, is the story we have been unfolding in this study, and which we are now ready to fit into the geologic time and the geographic areas in which speciation probably proceeded in the genus. ”

“ Their incompatibility may well be of the same nature as that of the classes in Cardamine pratensis.
Returning now to the problem of inter-specific sterility; we note, as I have said, the absence of contemporary evidence that variation can confer on a variety the power to form a sterile hybrid with the parent species. The considerations based on this want of evidence have for a long while been familiar to all who have discussed evolutionary theories, and it is worth observing the exact reason why the difficulty strikes us now with a new and special force. ”

“ In man and in domesticated animals we find that individuals appear occasionally that are defective in one or another respect. Some of the defects are inherited. Rarely a new one appears that has not been seen before. But the majority of them are reappearances of characters that have been carried under the surface as recessive genes in the germ-plasm. Today we recognize that each of these modifications, if recessive, has first arisen as a mutational change in a single gene before it appeared on the surface as a character by the coming together of two such genes. ”

“ These go over into the first generation hybrids, and are sorted out in the germ cells of the hybrid. Consequently, when the F1’s are inbred, there are all sorts of recombinations of the minor factors. This explains the greater variability of the second generation.
It is probable that in most of our domesticated animals, including man, much of the variability is due to multiple factors, which makes a study of inheritance in these groups extremely difficult, especially when, as in the case of man, the number of offspring from a pair is small, and critical combinations for study can not be made. ”

“ We do not know how widespread recessive genes are in the human germ-plasm. The fact that defective individuals appear in certain communities may be safely interpreted to mean that individuals bearing the same gene have at last come together. On the other hand, the absence of such individuals from the community, at large, may only mean that the chance of suitable combinations is small, and does not mean necessarily that the gene in question is confined to the community within which the defects have been recorded. ”

“ If we no longer see how varieties give rise to species, we may feel confident that a minute study of genetic physiology of varieties and species is the necessary beginning of any critical perception of their inter-relations. It is little more than a century since no valid distinction between a mechanical mixture and a chemical combination could be perceived, and in regard to the forms of life we may well be in a somewhat similar confusion.
As yet the genetic behaviour of animals and plants has only been sampled. ”

“ From the standpoint of heredity, however, the important consideration is to determine if these experimentally induced changes have been reflected on to the germ-cells so that they reappear in the offspring of the modified individuals.
It has been found that in some cases where male and female are of different color, the color of the female can be changed to that of the male by altering the conditions of temperature. In certain cases types can be changed by cold so that they resemble varieties of the same species found farther north, and by heat, varieties found farther south. ”

“ The recognition that disease genes are not a homogenous subset of human genes, and that essential genes cannot be excluded from consideration as candidates for all types of human disease genes, will aid in the identification of candidate disease gene loci for a variety of human diseases. ”

“ The concept of a mutation–selection balance is one of the oldest and most fundamental pillars of population genetics: natural selection increases the frequency of fit variants while mutations introduce unfit variants, giving rise to an equilibrium distribution balanced between these two effects. ”