3.4 进化和衰老

As we have seen, the longevity of a species is closely linked to genes selected for survival to reproductive age. Longevity has evolved. Conversely, the work of Medawar, Fisher, and Hamilton demonstrated that the slow decline in physiological function that is aging could not have arisen through natural selection. Aging has not evolved. This does not mean that genes have no role in the aging process. It simply means that genes related to the aging of a cell, tissue, organ, or organism were not subjected to the forces of 进化 for that specific purpose.

Recall that Medawar’s theory of mutation accumulation relies on evolution by genetic drift rather than on natural selection to explain aging in 进化 terms. His theory predicted that certain genes exist for the specific purpose of aging. We now know that aging does not have a basis in genetic determinism and, instead, reflects random and stochastic mechanisms (see Chapter 4). In this section we explore two theories of aging—antagonistic pleiotropic and disposable soma—that 进化arily account for age-related decline in physiological and biological function.

3.4.1 Antagonistic pleiotropy is a special case of general pleiotropy

Pleiotropy is a genetic mechanism in which a single gene produces more than one trait. For example, wild-type D. melanogaster has smoothed, curved bristles on its thorax, whereas the singed mutation, a single-point mutation, results in Drosophila with short, twisted bristles. In addition, the female singed mutant is sterile and produces ill-formed eggs (compared with the wild type) that never hatch. Therefore, in D. melanogaster, the lack of expression in one gene produces two phenotypes.

G.C. Williams combined the general concepts of pleiotropy with Medawar‘s declining force of natural selection to suggest a mechanism by which senescence can arise in a population in which genes are selected for reproductive success. This theory, antagonistic pleiotropy, predicts that genes conveying a benefit for fitness early in life will be selected even though they may be disadvantageous in later life. Williams summed up antagonistic pleiotropy as follows:

The selective value of a gene depends on how it affects the total reproductive probability [that is, over the entire life span]. Selection of a gene that confers an advantage at one age and a disadvantage at another will depend not only on the magnitudes of the effects themselves, but also on the times of the effects. An advantage during the period of maximum reproductive probability would increase the total reproductive probability more than a proportionately similar disadvantage later on would decrease it. So natural selection will frequently maximize vigor in youth at the expense of vigor later on and thereby produce a declining vigor. (Williams 1957)

Williams reaffirmed the importance of the declining force of natural selection as the basis for aging, and he placed prime importance on the timing of the effect. As we have seen, effects occurring early in the reproductive life span are strongly selected for, because of the large number of individuals involved in reproduction. If that same gene conveys a negative trait late in the life span, the lack of selection pressure (due to the limited number of viable reproductive members of the species) will allow the gene to be expressed and is, for all intents and purposes, selectively neutral. The gene will be selected because the benefit occurs during a time of high fitness, even if the detriment of the gene for the individual is significantly greater than the benefit provided early in the life span. That is, the trade-off between benefit and detriment of a pleiotropic gene will always favor the benefit, if it occurs at the right time in the reproductive life span.

At least two examples suggest the possibility of antagonistic pleiotropy in nature. First, the calcification of bone during fetal and childhood development imparts a reproductive advantage (protection of internal organs, body stability, etc.) and thus high fitness. Several genetic mechanisms that include hundreds of genes have been selected to ensure proper bone calcification. However, these same genes can be detrimental later in life, causing calcification of arteries during the postreproductive period, which can lead to coronary artery disease and myocardial infarction. Second, the Drosophila experiments described earlier in the chapter also provide evidence of antagonistic pleiotropy. In both experiments, the long-lived flies had fewer eggs, and the eggs where deformed (compared with those of the short-lived flies). Thus, the genetic mechanism that regulates normal egg production and development in short-lived flies must also have produced the problems associated with the eggs in the long-lived flies.

3.4.2 The disposable soma theory is based on the allocation of finite resources

Recall that August Weismann theorized that over 进化ary time, the soma had become mortal in order to support the immortal germ line. It was not until the early 1980s that scientists would pick up on Weismann's theory and develop a hypothesis to explain the underlying mechanism for the trade-off between the soma and the germ line. This hypothesis, first developed by Thomas Kirkwood, is known as the disposable soma theory.

The disposable soma theory is based on the 进化ary principle that all 环境s have finite resources, and organisms compete for those resources. The organisms that are the most efficient at using the available resources will survive, while inefficient organisms will die off. For example, imagine a time when protozoa (unicellular organisms) were beginning to evolve into metazoa (multicellular organisms). This would have been a time of great variation in the types of metazoa that were beginning to appear. The selection pressure would become more intense as the limited resources, such as food, were used up. The metazoan species that used the resources most efficiently would be the species to survive and pass on their genetic material to the next generation.

So what is the most efficient use of resources? The disposable soma theory suggests that the best use of resources is to give highest priority to the cells responsible for the continuation of the species, namely, the cells of reproduction, or the germ line. Supporting cells, those of the soma, would need only enough resources to ensure their primary job: supporting the survival of the germ line to the point of reproduction. That is, the soma could be disposed of once reproduction had occurred.

But, where and how are those resources being spent? Clearly, the production of a gamete would cost, in terms of energy, no more than the production of, say, a liver cell. Rather, the disposable soma theory predicts that early metazoans used available resources preferentially to maintain repair mechanisms of the DNA in the germ line. This suggestion arises from the current observation that it takes a lot of energy to ensure that the DNA sequence is correct. So, if we assume that an organism had to make an “进化ary choice” between accuracy in the DNA of the germ cell or some function of a somatic cell, maintaining the DNA of the germ cell would be the best chance for the survival of the species.

Unlike antagonistic pleiotropy, the disposable soma theory has not been tested experimentally. Rather, the disposable soma theory has been shown to be theoretically possible by describing how well it fits with established general 进化ary theory. In particular, this theory can be viewed as a special case of John Maynard Smith's optimality theory. Optimality theory predicts that an individual will optimize a behavior so that the cost associated with that behavior is minimized in accordance with the local 环境.

Optimality theory can be illustrated by species that lay eggs exposed to predation. The problem for these species is how to maximize the number of eggs that survive to hatching without investing more energy for the reproductive process than the 环境 will allow. Too few eggs, and they may all be lost to a predator; too many eggs, and insufficient nutrition to support egg production may result in “bad” eggs. The individual must arrive at a compromise to optimize survival of its offspring.

With regard to aging, at some point in 进化ary time, organisms had to “make a decision” about how much energy they should give to reproduction and how much to maintaining the soma. Too much energy diverted to accurate transmission of the genome to the next generation would result in not enough energy for maintaining the soma. The organism might not live long enough to successfully reproduce. Too much energy given to somatic maintenance, and the individual might live forever, but the accuracy of the genome would be compromised, eventually causing the extinction of the species. The disposable soma heory predicts that an organism will optimize resources so that there is high fidelity in the DNA of the gamete, with the leftover resources directed to maintenance of the soma. At some point during the postreproductive period, extrinsic aging will cause an accident to occur in the soma. The soma will not have the resources necessary to repair the function, and aging will ensue.

ESSENTIAL CONCEPTS

• August Weismann suggested that somatic cells need only live long enough to ensure survival to reproductive age. Once that job was done, there was no further need for the soma—and aging ensued.
• Weismann believed that because the detrimental effect of aging occurred after the start of reproduction, it was neutral with respect to selection pressure; that is, he though that aging neither increased nor decreased fitness.
• Population genetics defines two basic principles that affect the growth of a population: (1) the intrinsic rate of natural increase, r; and (2) the carrying capacity of a population, K.
• The values of r and K are used in the Verhulst-Pearl logistic equation, ,to describe population growth.
• Many species have K factors that are variable. For populations with variable K factors, age-structure analysis is used to determine population growth and its impact on fitness.
• The logistic equation and age-structure analysis show that species fitness is greatest at the time of the greatest rate in population growth (reproduction). This means that alleles that convey traits important to survival to reproductive age will be selected over alleles that impart longevity or aging.
• Sir Peter Medawar demonstrated that the force of natural selection declines with age.
• Genetic drift predicts that genes neutral to the force of natural selection can be fixed in a population as a result of the random sorting of alleles at the time of meiosis. Medawar suggested that genetic drift could work to select genes for aging.
• W.D. Hamilton established the mathematical foundation for the 进化ary theory of longevity by using a value he called the force of natural selection on mortality, s x . He suggested that genes that impart overall longevity for the individual must be related to genes selected for survival to reproductive age.
• Results of laboratory experiments support the mathematical and verbal predictions of Fisher, Medawar, and Hamilton and lead to the conclusion that both the intrinsic and extrinsic rates of aging are linked to the timing of reproduction, which, in turn, determines the length of the life span.
• G.C. Williams‘s theory of antagonistic pleiotropy predicts that genes that convey a benefit for fitness early in life will be selected even though they may be disadvantageous later in life.
• T.B. Kirkwood‘s disposable soma theory is based on the evolutionary principle that all 环境s have finite resources, and organisms compete for those resources. Organisms that are the most efficient at using the available resources will survive.

本章结束