Altering Developmental Trajectories in Mice by Restricted Index Selection

A restricted index selection experiment on mice was carried out for 14 generations on rate of early postnatal development (growth rate from birth to 10 days of age) vs. rate of development much later in ontogeny (growth rate from 28 to 56 days of age). Early rate of development (E) approximates hyperplasia (changes in cell number) and later rate (L) reflects hypertropy (changes in cell size). The selection criteria were as follows: E+L0 was selected to increase early body weight gain while holding late body weight gain constant; E-L0 was selected to decrease early body gain while holding late gain constant; E0L+ was selected to increase late gain holding early gain constant; and E0L- was selected to decrease late gain holding early gain constant. After 14 generations of selection, significant divergence among lines has occurred and the changes in the growth trajectories are very close to expectation. The genetic and developmental bases of complex traits are discussed as well as the concept of developmental homoplasy.     

Effect of selection for development rate on reproductive onset in female mice.

This research reports analyses of correlated response in reproductive onset in ICR mice after 23 generations of restricted index selection for divergent body weight gain, early (birth-10 days) or later (28-56 days) in life. Long-term selection altered growth trajectories and 56 day body weight of individuals under different selection regimes in this study. Mice in lines under early selection have the same percentage mature weight at vaginal opening as controls (63%). Vaginal opening is delayed in mice selected for slow early growth, which take longer to reach what appears to be a weight threshold. In contrast, individuals in lines selected for later slow growth undergo vaginal opening at the same age as controls, but at a lower weight and increased percentage mature weight. Pre-compensation or 'counter-balance growth' is observed in these lines, with mice selected for late enhanced growth reaching 52% of mature weight at vaginal opening while mice with late slow growth attain 71% of mature weight prior to vaginal opening. Only 42% of mice with late slow growth attain first oestrus by 56 days. We speculate this is a function of growth rate and fat/lean ratio. Mice with early slow growth show compensatory growth, reaching first oestrus at a similar time to controls. We conclude that selection for growth rate has asymmetrically affected reproductive onset, with lines selected for suppressed gains experiencing delays in the reproductive onset traits measured.     

Body weight and tail length divergence in mice selected for rate of development

A series of mouse lines has been produced by 19 generations of restricted index selection for rate of development during early and late ontogeny. The selection program was based on an index with the following four replicated selection treatments: E(+) and E(-) were selected to alter birth to 10-day body weight gain while holding late gain for both selection lines constant; correspondingly, L(+) and L(-) were selected to alter 28- to 56-day body weight gain holding early gain for both lines constant. Herein, we characterize response to selection for growth rate by analyzing age-specific mouse body weight and tail lengths and for growth curves using a logistics model. Selection on developmental rate has resulted in divergence in both age-specific and growth curve traits. E(+) and L(+) lines reached identical weights during the late selection interval, then diverged to unique mature weights. E(-) and L(-) lines similarly achieved identical weights during late selection and diverged to unique mature weights. However, the shapes of early and late growth curves were significantly divergent, and at least two distinct growth patterns are shown to result from selection. Response in body weight gain was accompanied by similar, though less pronounced, change in tail length traits. Significant response during intervals of restricted growth was also found, especially in lines selected for late gain. The evolution of the growth trajectory under restricted index selection is discussed in terms of drift and available additive genetic variation and covariation.     

Allocation of cells to proliferation vs. differentiation and its consequences for growth and development

A model relating the recruitment of skeletal muscle fibers from precursor cells to growth and development of the whole muscle is presented. The pattern of growth throughout ontogeny is analyzed for differences in: (1) initial number of precursor cells, (2) timing of onset of differentiation, (3) timing of offset of differentiation, and (4) differentiation rate (number of precursor cells that differentiate each cell cycle). The initial number results in a larger muscle but has no effect on relative growth rate. Later onset time and slower differentiation rate result in relatively slow growth early in ontogeny but rapid growth for most of ontogeny. A later offset time results in faster growth late in ontogeny as new fibers continue to be recruited late into ontogeny. The pattern derived from onset time and differentiation rate matches that of the precocial-altricial continuum in birds in which selection for functional ability early in ontogeny results in slow growth late in ontogeny. Methods for recognizing the different developmental parameters in the size distribution of muscle fibers are described and three empirical examples interpreted in terms of the model.     

Endopolyploidy as a morphogenetic factor of development

This paper summarizes the works published by author and his co-workers in the Russian journal Tsitologiya concerning endopolyploidy in mollusks and appraises this phenomenon in general. Both ontogenetic and phylogenetic aspects of endopolyploidy have been studied. In the snail Succinea lauta, a complex examination of endomitosis has been performed. A regular replacement of the normal (complete) proliferative mitosis by abnormal (incomplete) restitutional mitosis, and then by Geitler's classic endomitosis has been demonstrated. We examined 29 bivalve and 82 gastropod species for the presence of polyploid cells in glandular tissues and ganglia. In the bivalve species, ordinary diploid cells form various tissues, while in the gastropods, the role of polyploidy in tissue development appears to increase in phylogenesis. The rise of endopolyploidy and cell giantism in histogeneses of a variety of animal and plant species is widely known. It is believed to be a regular event in the evolution of certain groups. To give a universal interpretation of endopolyploidy, we proposed that a single polyploid cell be better considered as an endoclone. In this case, evolutionary transformation of diploid cell clones into polyploid endoclones may be viewed as Dogel's oligomerization applied to cell-tissue level. From this viewpoint, major properties of an oligomerized system (intensification of function, functional efficiency (ergonomy), increased genomes reliability, simplification of the intra- and supersystem regulations, and acceleration of development) can be considered as principal peculiarities of polyploid growth strategy. The above peculiarities allow one to consider endopolyploidy as an additional means of integrative onto(histo)genetic regulations and correlations and as an important evolutionary factor (coordinations) acting through natural selection. Thus, in general, endopolyploidy is an adaptive morphogenetic factor, but its concrete role may differ in different tissues and organisms depending on cell specialization and histogenetic particularities.     

Cellular consequences in the brain and liver of age-specific selection for rate of development in mice

Changes in cell number (hyperplasia) and cell size (hypertrophy) in the brain and liver are described for mice subjected to 24 generations of age-specific restricted index selection for rate of development in body weight. One selection treatment (E) altered rate of development between birth and 10 days of age, another treatment (L) involved changes in rate of development between 28 and 56 days of age, while a third control treatment (C) involved random selection. Each selection treatment was replicated three times. These age-specific selection treatments focused on intervals during ontogeny when different developmental processes (hypertrophy or hyperplasia) were more predominant in the control of growth. Significant changes in brain and liver weight occurred at both 28 and 70 days of age. Early selection (E) generated significant changes in the number of cells in the brain while later selection (L) had no effect since the brain had stopped growth before selection was initiated. For the liver, early and late selection produced significant effects on both cell number and cell size. These results describe the dynamic and multidimensional aspects of selection in terms of its ability to alter different cellular and developmental components of complex morphological traits.     

A correlated response of a parasite’s virulence and life cycle to selection on its host’s life history

We demonstrate a correlated response of the virulence and the mode of transmission of the microsporidian parasite Edhazardia aedis to selection on the age at pupation of its host, the mosquito Aedes aegypti. We selected three lines of mosquitoes each for early or late pupation and exposed the larvae after zero, two and four generations of selection to a low and a high concentration of the parasite’s spores. Before selection the parasites induced a similar level of mortality in the six lines; after four generations of selection mortality was higher in the mosquitoes selected for late pupation than in those selected for early pupation. Overall, parasite-induced mortality was positively correlated with the mean age at pupation of the matching uninfected line. When they died, mosquitoes selected for early pupation harboured mostly binucleate spores, which are responsible for vertical transmission. Mosquitoes selected for late pupation were more likely to harbour uninucleate spores, which are responsible for horizontal transmission. The parasite enhanced this tendency for horizontal transmission by prolonging the larval period in the lines selected for late pupation, but not in the ones selected for early pupation. These results suggest that the genetic basis of the mosquito’s age at pupation helps to determine the parasite’s mode of transmission: parasites in rapidly developing mosquitoes are benign and transmit vertically, while parasites in slowly developing mosquitoes are virulent and transmit horizontally. Thus, as the host’s life history evolves, the parasite’s performance changes, because the host’s evolution changes the environment in which the parasite develops.     

Genetic Divergence under Uniform Selection. II. Different Responses to Selection for Knockdown Resistance to Ethanol among DROSOPHILA MELANOGASTER Populations and Their Replicate Lines

We have tested the hypothesis that genetic differences among conspecific populations may result in diverse responses to selection, using natural populations of Drosophila melanogaster. Selection for ethanol tolerance in a tube measuring knockdown resistance was imposed on five West Coast populations. In 24 generations the selected lines increased their mean knockdown times, on average, by a factor of 2.7. An initially weak latitudinal cline was steepened by selection. The two southernmost populations showed the same increases in the selected character, but differed consistently in their correlated responses in characters related to ethanol tolerance. This result indicates that the populations responded to selection by different genetic changes. Selection decreased female body weight and increased resistance to acetone, suggesting components of the response unrelated to ethanol metabolism. The Adhs allele was favored by selection in all populations at the onset, but increased in frequency only in the selected lines of the southernmost population. There was a correlation between latitude and Adh frequency changes, suggesting that fitnesses of the Adh alleles were dependent on the genetic background. Genetic background also had a large effect on the loss of fitness due to selection. Genetic drift between replicate lines caused more variation in selection response than initial genetic differences between populations. This result demonstrates the importance of genetic drift in divergence among natural populations undergoing uniform selection, since the effective population sizes approached those of small natural populations. Drift caused greater divergence between selected replicates than control replicates. Implications of this result for the genetic model of selection response are discussed.     

An Experimental Study of Cell and Nuclear Growth and Their Relation to Cell Diversification within a Plant Tissue

Roots of Zea mays were grown for four days in a solution of colchicine that inhibits cell division. During this period the amount of cell growth and nuclear DNA replication was measured in different regions of the root cap. The rates at which cell volume and nuclear DNA content double are similar in the first cell-tier of the cap (the meristematic stem-cell) but in more distal cells the rate of cell growth outstrips the rate of nuclear DNA increase. It is suggested that the degree of coordination between cell and nuclear growth regulates meristematic activity and can influence the onset of cell differentiation.
The pattern of endopolyploidy changes in the different regions of the colchicine-treated root cap. It is suggested that the degree of endopolyploidy normally characteristic of cells at particular locations within this tissue is not a response to a positional signal alone; it is more likely to be due to some rate-limiting control of DNA synthesis.     

Uterine and postnatal maternal effects in mice selected for differential rate of early development.

A series of mouse lines was produced by long-term restricted index selection for divergent rate of growth during early and late postnatal development. The selection program was based on the following treatments: E(+) and E(-) lines were selected to alter birth to 10-day weight gain while holding late gain for both lines constant and a control line was established via random selection. Using embryo transfer and crossfostering methodology, we partitioned postnatal growth for E(+), E(-), and C lines into progeny genetic, uterine maternal, and nurse maternal components. Selection for differential early growth resulted in correlated response in uterine and nurse maternal effects on body weights, with significant genetic-by-environment interactions. Significant uterine effects were also observed in tail length measurements. Direct uterine effects on body weight were relatively small and resulted in growth rate differences early in development. Nurse effects were large, resulting in modification of progeny growth trajectory especially during early postnatal development. Genetic-by-uterine interactions were large and demonstrate progeny-specific effects of the prenatal uterine environment.     

Food Consumption, Feed Efficiency, Metabolic Rate and Utilization of Glucose in Lines of TRIBOLIUM CASTANEUM Selected for 21-Day Pupa Weight

Growth rate, body composition, cell number, cell size, and the activity of four dehydrogenase enzymes were studied from 10 to 25 days of age in one control (1C) and three lines (3, 9, 10) of Tribolium castaneum that had been subjected to long term selection for large 21-day pupae weight.—Selected lines were two- to three-fold larger in size than the control line throughout development. No major differences in percent of protein were detected among the lines but at any particular age, the selected lines were found to have a higher fat content than the control line. The differences in fat content were closely correlated with development such that all the lines reached very similar levels of percent of fat just prior to pupation. Water content showed an inverse relation to percent of fat.—Selection was observed to have caused major changes in the cellular response to growth. The selected lines had an average of from 17% to 48% larger cells (measured as protein/DNA) and were found to have from 37 to 62% more cells (measured as total DNA) than the control line at all ages from 10 to 19 days of age. In addition, the selected lines had a higher RNA content at all ages studied and higher RNA:DNA ratios at the young ages. In contrast the enzyme activities of ICDH and LDH were 60% lower. The results are interpreted as indicating that a more efficient metabolic machinery had evolved in the rapidly growing selected lines.     

Endopolyploidy in seed plants

Two main attempts have been suggested for the biological significance of endopolyploidy: (i) provision of high DNA amounts to support high synthetic demands in certain cells and (ii) compensation for a lack of nuclear DNA in species with small genomes. However, in seed plants, the positive correlation between DNA content and cell volume of endopolyploid cells suggests other possibilities. Cell size paralleled by the endopolyploidy level has an impact on growth and development. Endopolyploidy levels in turn are characteristic for a given species and even families, reflecting the adaptation to certain habitats during phylogeny. Furthermore, endopolyploidy levels vary to some degree between individuals of one species in response to different environmental conditions. In addition, endopolyploidy differs between different tissues suggests that a certain cell size is advantageous for a given cell function. This article reviews these findings and discusses more conclusive possible functions of endopolyploidy.     

CORRELATED RESPONSE IN THE DEVELOPMENTAL CHOREOGRAPHIES OF THE MOUSE MANDIBLE TO SELECTION FOR BODY COMPOSITION

The correlated response to 13 generations of selection for percent fatness and leanness is investigated in 11 mandible traits in mice. Five selection lines are examined including high fat (HF), low fat (LF), high lean (HL), low lean (LL) and a randomly selected control strain (RC. The ontogenetic patterns of growth in the RC strain serve as a model to evaluate the developmental consequences of directional selection. Selection has systematically altered the patterns of mandible growth in selection lines relative to the control strain. Further, selection has significantly altered the age-specific phenotypic covariance among these traits. In the HF strain, growth in the mandible is completed by 12 weeks of age for most traits. In other selected strains, notably LF and LL, there is a significant growth spurt that occurs between 12 and 15 weeks of age. Changes in the patterns of mandibular growth produce significant differences among strains in the final form of the mandible. Because of the changes in the patterns of growth, the differences among strains are themselves shown to vary at different postnatal ages. The phenotypically similar strains, i.e., HF and LL or LF and HL, show different but correlated patterns of divergence. Multivariate statistical analyses suggest that the temporal strain differences in these traits are multidimensional.     

Evolutionary relationship of fat body endoreduplication and queen fecundity in termites

Endoreduplication or nuclear genome replication without cell division is widely observed in the metabolically active tissues of plants and animals. The fat body cells of adult female insects produce abundant yolk proteins and become polyploid, which is assumed to accelerate egg production. Recently, it was reported that in termites, endopolyploidy in the fat body occurs only in queens but not in the other females; however, the relationship between the fecundity and ploidy level in the fat body remains unclear. Termite queens exhibit a huge variation in their egg‐producing capacity among different species; queens in the species with a foraging lifestyle, in which workers leave the nest to forage outside, are much more fecund than those in the species living in a single piece of wood. In this study, we conducted ploidy analyses on three foragings and three wood‐dwelling termites via flow cytometry. In all the species, the fat body of queens contained significantly more polyploid cells than that of other nonreproductive females, considering their body size effect. However, the male fat body, which is not involved in yolk production, did not show consistency in polyploid cell numbers among the species studied. Moreover, highly fecund queens in foraging termites exhibit higher levels of endopolyploidy in their fat body than those with less fecundity in wood‐dwelling termites. These results suggest that endopolyploidy in the fat body of termite queens can boost their egg production, and the level of endopolyploidy in their fat body is linked to their fecundity. Our study provides a novel insight into the evolutionary relationship between endoreduplication and caste specialization in social insects.     

Growth Rate, Body Composition, Cellular Growth and Enzyme Activities in Lines of TRIBOLIUM CASTANEUM Selected for 21-Day Pupa Weight

Growth rate, body composition, cell number, cell size, and the activity of four dehydrogenase enzymes were studied from 10 to 25 days of age in one control (1C) and three lines (3, 9, 10) of Tribolium castaneum that had been subjected to long term selection for large 21-day pupae weight.-Selected lines were two- to three-fold larger in size than the control line throughout development. No major differences in percent of protein were detected among the lines but at any particular age, the selected lines were found to have a higher fat content than the control line. The differences in fat content were closely correlated with development such that all the lines reached very similar levels of percent of fat just prior to pupation. Water content showed an inverse relation to percent of fat.-Selection was observed to have caused major changes in the cellular response to growth. The selected lines had an average of from 17% to 48% larger cells (measured as protein/DNA) and were found to have from 37 to 62% more cells (measured as total DNA) than the control line at all ages from 10 to 19 days of age. In addition, the selected lines had a higher RNA content at all ages studied and higher RNA:DNA ratios at the young ages. In contrast the enzyme activities of ICDH and LDH were 60% lower. The results are interpreted as indicating that a more efficient metabolic machinery had evolved in the rapidly growing selected lines.     

A genetic correlation between age at pupation and melanization immune response of the yellow fever mosquito Aedes aegypti

To investigate the evolutionary cost of an immune response, we selected six lines of the mosquito Aedes aegypti for earlier or later pupation and measured the extent to which this selection procedure changed the mosquito's ability to encapsulate and melanize a negatively charged Sephadex bead. After 10 generations of selection, the age at pupation in the two selection regimes differed by about 0.7 days, accompanied by an increase of wing length of the mosquitoes selected for late pupation. Among the mosquitoes that had been selected for early pupation, only 6% had strongly or completely melanized the bead, while among the individuals that had been selected for late pupation, 32% had melanized the bead. Thus, our results suggest a genetic correlation between age at pupation and immunocompetence. As a consequence, mosquitoes that respond to increased intense parasite pressure with more effective immunity are predicted to pay for the increased defense with slower development.     

De novo variation in life-history traits and responses to growth conditions of resynthesized polyploid Brassica napus (Brassicaceae)

Variation that arises in generations immediately following polyploidization may be important for the establishment, adaptation, and persistence of new polyploid species. We previously showed divergence for flowering time among lines from a resynthesized Brassica napus allopolyploid lineage derived from a cross of diploid B. rapa and B. oleracea. In this study, we more fully assess phenotypic differentiation of lines from the previously studied lineage and of lines derived from an additional resynthesized B. napus lineage. Nine polyploid lines and their diploid parents were grown under four growth conditions and measured for eight life-history traits. Polyploid lines within a lineage were expected to be genetically identical because they were derived from individual, chromosome-doubled amphihaploid plants. However, significant differences were found among lines within lineages for every phenotypic trait measured and in response to different growth conditions (genotype by environment interactions). When phenotypes of each polyploid line for each trait in each environment were compared with their diploid progenitors, approximately 30% were like one or the other parent, 50% were intermediate, and 20% were transgressive. Our results demonstrate extensive de novo variation in new polyploid lineages. Such changes could contribute to the evolutionary potential in naturally occurring polyploids.     

Ontogeny of Cell-Mediated Immunity of Murine Thymocytes and Spleen Cells

The ontogeny of cell-mediated immunity of spleen cells and thymocytes from B10 mice was studied in both in vitro mixed leukocyte culture and cell-mediated lympholysis reactions. Results show that newborn spleens contain cells competent to respond to X-irradiated allogeneic spleen cells in mixed leukocyte culture. The mixed leukocyte culture response of spleen cells, in terms of both index of stimulation and increment of tritiated thymidine incorporation, seems to be higher for mice four weeks or older than for mice less than four weeks old. The cell-mediated lympholysis response of spleen cells is not detectable until two days postpartum. It reaches adult levels in terms of % cytolysis by day four after birth. Thus, the transition period of the ontogeny of cell-mediated lympholysis response of spleen cells is apparently 0–4 days of age.
Newborn and early postnatal thymocytes (0–7 days of age) respond in mixed leukocyte culture at least as strongly as adult thymocytes (2–3 months of age). The cell-mediated lympholysis response of thymocytes is already detectable at birth, but weaker in terms of % cytolysis when compared with the cell-mediated lympholysis response of thymocytes from two days to six weeks of age. The cell-mediated lympholysis response of thymocytes starts to decline at 6–8 weeks of age. Thus, around the time of birth, there is a transition period in the cell-mediated lympholysis response of thymocytes during which thymocytes start to show high cell-mediated lympholysis reactivity. There is a second transition period between six and eight weeks of age during which the cell-mediated lympholysis response of thymocytes diminishes. The early, as well as late, postnatal cell-mediated lympholysis response of both spleen cells and thymocytes seems to be specific in nature.     

The effects of selection for different combinations of weights at two ages on the growth curve of mice

Summary The weights of mice in lines selected for different combinations of high and low body weights at 5 and at 10 weeks of age were recorded from 3 to 21 weeks of age. The average growth curve for each line was computed using the Gompertz function. The growth curves of lines selected for high or low weight at a single age (ST lines) showed large differences in estimates of mature size and small differences in estimates of maturing rate, i.e. of the relative rate of growth to maturity. The growth curves of lines selected by independent culling for divergent combinations of deviations of opposite sign in 5- and 10-week weights (ICL lines) showed little difference in estimates of mature size and a large difference in estimates of maturing rate. The growth curves of lines selected by index for divergence in 5-week weight with no change in 10-week-weight or for divergence in 10-week-weight with no change in 5-week weight showed large differences in estimates of mature size and large differences in estimates of the maturing rate. The relationship between mature size and maturing rate was affected in different ways by the three types of selection.     

GIBBERELLIN RELATIONSHIPS IN THE ‘ALASKA’ PEA (PISUM SATIVUM)

'Alaska’ peas (Pisum sativum L.) grown under a 16-hr photoperiod at 20 ± 1 C and an 8-hr dark period at 16 ± 1 C in their ontogeny exhibit two periods of sensitivity to applied gibberellin (GA), namely, prior to and subsequent to but not during the linear phase of stem elongation. This paper describes experiments conducted primarily with seedlings. Growth-saturating doses of GA, applied to dry seeds before planting (10⁻³ m) and to the shoot tips of 3-day-old seedlings (10 μg), evoked growth rates equal to the growth rate of etiolated seedlings. Sensitivity of seedlings to applied GA decreased with age through the first 2 to 3 weeks of development; by the time seedlings were about 14 days of age and had four elongating internodes they no longer responded to applied GA. As endogenous growth rate diminished late in ontogeny, the plants again became sensitive to applied GA. Growth response was used as a criterion for determining apparent translocation of applied GA. ‘Alaska’ pea seedlings appeared to transport GA, both acropetally from the cotyledons and basipetally from the shoot tip, to all internodes with remaining extension potential. Excision of both cotyledons at any time during the first 9 days of development caused a significant reduction of growth rate, and applied GA did not restore normal growth rate. No evidence was found that the cotyledons supply endogenous GA to the shoot axis in normal seedling development. It is suggested that the normal growth rate of light-grown ‘Alaska’ peas is correlated with the rate of synthesis of GA and that GA is rate-limiting for stem elongation during early seedling development and during the period of decreasing growth rate and onset of apex senescence.