The Genetic Structure of the Raleigh Natural Population of Drosophila melanogaster Revisited

Corresponding author: Shinichi Kusakabe, Department of Biology, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan., sakusa{at}ipc.hiroshima-u.ac.jp (E-mail)

Communicating editor: M. J. SIMMONS

	ABSTRACT

TOP ABSTRACT MATERIALS AND METHODS RESULTS AND ANALYSES DISCUSSION LITERATURE CITED

The Raleigh natural population of Drosophila melanogaster was reanalyzed with special attention to possible dysgenic effects during the extraction of chromosomes. About 600 second chromosomes were extracted from the Raleigh natural population, half in the cytoplasm of wild-caught females (native genetic background) and half in the cytoplasm of the laboratory line, C160(In(2LR)SM1, Cy/In(2LR)bw^V1) (foreign genetic background). We could not find significant differences between the two extraction schemes in the frequency of lethal second chromosomes (Q = 0.252 for the lines with the negative genetic background vs. 0.231 for the lines with the foreign genetic background) or in the homozygous detrimental (D) and lethal (L) loads (D = 0.210 vs. 0.251; L = 0.287 vs. 0.264). The effective size of the population was estimated to be ~19,000, based on the allelism rate of lethal-bearing chromosomes. The homozygous load markedly decreased in the 15 years since a previous study of the same population.

GENETIC variation in viability in the Raleigh natural population of Drosophila melanogaster was intensively studied in the early 1970s by Mukai and his colleagues (MUKAI et al. 1972 , MUKAI et al. 1974 ; MUKAI and YAMAGUCHI 1974 ; WATANABE et al. 1976A ; MUKAI and VOELKER 1977 ). One remarkable finding was the greater homozygous viability load compared to the loads observed by Crow and his colleagues in Wisconsin (GREENBERG and CROW 1960 ; HIRAIZUMI and CROW 1960 ; TEMIN et al. 1969 ), although the ratio of the detrimental load to the lethal load was not much different in the different studies. The further analysis of the Orlando-Lake Placid, Florida population in 1972 revealed a larger homozygous viability load (MUKAI and NAGANO 1983 ).

In the course of these studies, phenomena such as appreciable frequencies of unique inversions (CHIGUSA et al. 1969 ), an unexpectedly high spontaneous mutation rate (CARDELLINO and MUKAI 1975 ), and the spontaneous occurrence of chromosomal aberrations (YAMAGUCHI et al. 1976 ) suggested that some kind of mutator (IVES 1950 ) existed in the southern populations. Meanwhile, the phenomenon of hybrid dysgenesis was discovered (KIDWELL et al. 1977 ; reviewed in ENGELS 1997 ) and is now known to cause a high spontaneous mutation rate (KIDWELL et al. 1973 ; MUKAI et al. 1985 ; YUKUHIRO et al. 1985 ; MACKAY 1987 ), hybrid sterility (ENGELS 1979 ), male recombination (YAMAGUCHI and MUKAI 1974 ), and chromosomal aberrations (SIMMONS and LIM 1980 ). Analyses in the Katsunuma, Japan population (MUKAI et al. 1985 ) suggest the possibility that the dysgenic effect during chromosome extraction could inflate the estimate of the homozygous viability load of a natural population. Thus, we have reanalyzed the Raleigh natural population to estimate various population genetic parameters, paying special attention to the effect of the genetic background during chromosome extraction.

The studies on the genetic structure of the Raleigh natural population (MUKAI and YAMAGUCHI 1974 ) were originally undertaken to characterize a control population that could be used to assess the effects of environmental mutagens in the future. Because the Raleigh population has been studied extensively, it is valuable to reanalyze it to determine whether any changes have occurred since the original studies. Thus, the aims of the present study were: (1) to determine whether the large homozygous load observed in the 1970s is characteristic of the Raleigh natural population per se or confounded with mutational events caused by hybrid dysgenesis at the time the chromosomes were extracted and (2) to determine whether the genetic structure of the Raleigh natural population has changed.

	MATERIALS AND METHODS

TOP ABSTRACT MATERIALS AND METHODS RESULTS AND ANALYSES DISCUSSION LITERATURE CITED

Extraction of second chromosomes:
About 400 female flies were collected in the fall of 1984 in Raleigh, North Carolina by Cathy C. Laurie to establish a series of isofemale stocks, each cultured in a vial, maintained in a room at 18°. Within five generations, ~300 second chromosomes were independently extracted both in the wild cytoplasm and in the laboratory (M cytotype) cytoplasm of the Cy/Pm (C160; In(2LR)SM1, Cy/In(2LR)bw^V1) stock from each isofemale stock, using the marked inversion method (Figure 1). Thus, ~600 second chromosomes in total were established as isogenic lines with respect to the second chromosomes; half of them had the wild cytoplasm and half had the Cy/Pm cytoplasm. These two types of lines are hereafter called the native and foreign strains, respectively. These isogenic lines were maintained at 18° and served in the following experiments carried out in 1985–1986. Some of the results were presented at the 58th Annual Meeting of the Genetic Society of Japan (1986).

View larger version (53K): In this window In a new window Download PPT slide   Figure 1. Mating scheme for the extraction of second chromosomes from the Raleigh natural population (1984). The shaded area indicates origin from the wild isofemale line and the white area indicates origin from the experimental stock C160(Cy/Pm).

Cytological examination and enzyme assay:
All of the salivary gland chromosomes of the established lines were examined for chromosomal aberrations after crossing with a cn bw stock, which has the standard arrangement of bands on the second chromosome. For the electrophoretic survey, the following five enzyme loci located on the second chromosome were examined: -glycerol-3-phosphate dehydrogenase (GPDH, map position 2-17.8), malate dehydrogenase (MDH, 2-35.3), alcohol dehydrogenase (ADH, 2-50.1), hexokinase-C (HEX-C, 2-74.5), and -amylase (AMY, 2-77.3). The four dehydrogenases were assayed by starch gel electrophoresis (SHAW and PRASAD 1970 ), whereas -amylase was assayed by acrylamide gel electrophoresis (PRAKASH et al. 1969 ).

Estimation of the rate of allelism among lethal chromosomes:
For estimating the effective size of the population, allelism tests among lethal chromosome lines were carried out using 74 complete lethal chromosomes from the native strains. Crosses were made between Cy/l_i and Cy/l_j, where l indicates a lethal-bearing chromosome, and subscripts i and j are the line numbers.

Estimation of relative viabilities and homozygous viability load:
Homozygous and heterozygous viabilities were estimated with the Cy method as in WALLACE 1956 . The procedure for the estimation of viability was the same as in MUKAI and YAMAGUCHI 1974 . Crosses for estimating homozygous viabilities were made between five Cy/+_i females and five Cy/+_i males with two simultaneous replications in each chromosome line, where i indicates the line number. Crosses for estimating random heterozygous viabilities were simultaneously made between five Cy/+_i females and five Cy/+_i+1 males (i = 1 - n), where n is the number of lines in one set of the experiments. In the offspring of both crosses, the expected segregation ratio of Cy to wild type is 2:1. Relative viability was calculated as 2b/(a + 1), where b is the number of wild-type flies and a the number of Cy flies, and the 1 in the denominator is HALDANE 1956 correction for bias in averaging ratios. All of the estimated viabilities were standardized by the mean viability of the heterozygotes.

Reanalyses of the viability data from the 1970s sample of flies:
The late Professor Terumi Mukai left the original data of viability studied by MUKAI and YAMAGUCHI 1974 . We analyzed these data, paying special attention to the genetic background of the extracted lines. In Mukai and Yamaguchi's study, as shown in Figure 2 (right), wild-caught male flies were individually crossed to five Cy/Pm (C160) females with typical laboratory cytoplasm, and randomly chosen F₁ Cy/+ males with the cytoplasm of the Cy/Pm laboratory stock were individually backcrossed to Cy/Pm females to establish lines with isogenic second chromosomes. In addition, wild-caught females were crossed with Cy/Pm males to extract second chromosomes (Figure 2, left). In this case, however, the cytoplasm of the F₁ Cy/+ male used to establish the line was that of the wild stock. We call the first set of lines the male-originated lines and the second set the female-originated lines. In both sets, the cytoplasm of the established lines was derived from the Cy/Pm stock. Viabilities were estimated as described above except that there were four simultaneous replications instead of two. We reanalyzed all the viability data of MUKAI and YAMAGUCHI 1974 and estimated the mean homozygous viabilities of the female-originated lines and the male-originated lines separately.

View larger version (44K): In this window In a new window Download PPT slide   Figure 2. Mating scheme for the extraction of second chromosomes from the Raleigh natural population (1970). The shaded area indicates origin from the wild-caught female or male and the white area indicates origin from the experimental stock C160(Cy/Pm).

	RESULTS AND ANALYSES

TOP ABSTRACT MATERIALS AND METHODS RESULTS AND ANALYSES DISCUSSION LITERATURE CITED

Genetic variation in the 1984 Raleigh population:
The frequencies of fast (F) electrophoretic alleles and inversions are shown in Table 1 in comparison with those observed between 1968 and 1974 in the same population (MUKAI et al. 1971 , MUKAI et al. 1974 ; MUKAI and VOELKER 1977 ). Most of the frequencies had not changed over 17 years. The frequency of In(2L)t is significantly different at the 5% level between 1968–1974 and 1984, but not significantly different between 1974 (0.070 ± 0.010 in MUKAI and VOELKER 1977 ) and 1984 (0.090 ± 0.012). A highly significant difference in the frequency of unique inversions was seen between 1968–1974 and 1984.

Effective size of the 1984 Raleigh population:
The allelism rate of lethals is estimated to be 0.0061 (16/2638) using 74 lethal chromosomes derived only from the native strains. The effective size of the population (N_e) can be estimated by NEI's formula (NEI 1968 ),

where l_g stands for the allelism rate of lethal genes and is estimated by

where l_c stands for the allelism rate of lethal chromosomes, U is the total lethal mutation rate, and Q is the frequency of the lethal chromosomes.

With these formulas, the effective size of the population (N_e) was estimated to be ~19,000, assuming the lethal mutation rate (U) per second chromosome per generation to be 0.005 and the rate per locus (µ) per generation to be 10^-5 (CROW and TEMIN 1964 ). The estimates on effective population size are listed in Table 2 along with those with 1968 and 1974 (MUKAI and YAMAGUCHI 1974 ; MUKAI and VOELKER 1977 ). These estimates and the present estimates are not much different from each other, although the one estimate from 1970 is large.

Distribution of viabilities and estimation of homozygous viability load:
About 300 lines from both the native (329 lines) and foreign (281 lines) strains were examined for their homozygous and heterozygous viabilities. The average of the unstandardized heterozygous viabilities was 1.072 ± 0.082 for the foreign strains and 1.059 ± 0.078 for the native strains. The average of the unstandardized homozygous viabilities was 0.640 ± 0.070 for the foreign strains and 0.645 ± 0.069 for the native strains. These are not significantly different. The frequency distributions of the standardized viabilities are shown in Figure 3. By the Kolmogorov-Smirnov nonparametric test, there is no significant difference in the distribution patterns between the native and foreign strains (P > 0.20).

View larger version (28K): In this window In a new window Download PPT slide   Figure 3. The distributions of homozygote and heterozygote viabilities for the second chromosomes with different genetic backgrounds.

The frequencies of lethal-carrying second chromosomes with viability <0.05 were 0.237 ± 0.023 (78/329) for the native strains and 0.231 ± 0.025 (62/281) for the foreign strains. These are not significantly different from each other. However, in 1970 (MUKAI and YAMAGUCHI 1974 ) the frequency of lethal-carrying chromosomes was 0.375 ± 0.019 (259/291). Thus, it has decreased in 15 years.

The averaged standardized viability of all homozygous lines (B), that of the homozygous lines excluding the lethal chromosomes (C), and that of the homozygous lines with viability indices >0.6 are shown in Table 3. There are no significant differences in the average homozygous viabilities from the native and foreign strains. The total homozygous load (T), detrimental load (D), and lethal load (L) were calculated using the formulas given by GREENBERG and CROW 1960 :

The estimates are shown in Table 3. We find a marked decrease in the homozygous viability load between 1974 (Table 4) and 1984, reflecting a decrease in both the lethal and detrimental loads. However, the D:L load ratio is not much different between these years.

View this table: In this window In a new window   Table 4. Reanalyzed homozygous loads in the Raleigh natural population in MUKAI and YAMAGUCHI 1974

Distribution of viabilities in 1970s sample:
In the study of MUKAI and YAMAGUCHI 1974 , the extraction method of the second chromosomes was slightly different between the wild-caught females and males. Viability distributions of the female-originated lines and the male-originated lines are graphically presented in Figure 4. By the Kolmogorov-Smirnov nonparametric test, these distribution patterns were not significantly different (P > 0.2). The heterogeneity of the distribution patterns was also tested by a ² test. Because the small number of members in the classes inflates the ² value, we lumped the classes with members 5 with an adjacent class to create classes of adequate size for the test. The number of classes was reduced from 12 to 9. The ² value was estimated to be 8.19 (d.f. = 8, 0.5 < P < 0.6), which is not significant. The frequencies of lethal-carrying chromosomes were 0.384 ± 0.025 (141/367) for the female-originated lines and 0.364 ± 0.027 (118/324) for the male-originated lines. These two estimates are not significantly different from each other.

View larger version (23K): In this window In a new window Download PPT slide   Figure 4. The distributions of homozygote viabilities for the second chromosome samples derived from the wild-caught females and from the wild-caught males (data from MUKAI and YAMAGUCHI 1974 ).

The average relative viability of all homozygous lines (B), that of the homozygous lines excluding those with lethals (C), and that of the homozygous lines with viability indices >0.6 are shown in Table 4. There are no significant differences in the average viabilities of homozygous lines between the female-originated and male-originated lines. The total homozygous load (T), detrimental load (D), and lethal load (L) were calculated based on these estimates and are shown in Table 4. Thus, we could not detect any differences between the two types of chromosomal lines derived by different extraction schemes.

	DISCUSSION

TOP ABSTRACT MATERIALS AND METHODS RESULTS AND ANALYSES DISCUSSION LITERATURE CITED

The significant findings in this study:
(1) The homozygous load (detrimental and lethal loads) was not different between strains derived by two different extraction schemes (the native lines and the foreign lines) for the second chromosome samples in 1984; (2) the homozygous load of the Raleigh population had greatly decreased during 15 years, although other estimates of the population genetic parameters had not changed.

The dysgenic effect of the cytoplasm-chromosome interaction on homozygous loads in different genetic backgrounds:
We had tested the cytotype of the Cy/Pm (C160) stock used in the present study and found it to be the M type (YUKUHIRO et al. 1985 ). Thus, if the P-M type of hybrid dysgenesis had occurred during the extraction of the second chromosomes, we might have detected differences in the estimates of homozygous loads between the two sets of strains. A difference was not detected in any estimate of the average homozygous viabilities between the native and foreign strains. The dysgenesis-induced lethal mutation rate is reported to be 0.031 per second chromosome per generation (CARDELLINO and MUKAI 1975 ). This estimate was obtained using chromosome lines extracted from the Raleigh population and maintained in the Cy/Pm cytoplasm. It was also estimated by SUH and MUKAI 1987 to be ~0.090 (51/566) per second chromosome each generation by studying lethal mutations that were induced on the second chromosomes of a typical P strain derived from the Ishigakijima natural population in the Cy/Pm cytoplasm (M type). Another estimate of the lethal mutation rate of the ₂ strain is 0.067 per second chromosome per generation (YUKUHIRO et al. 1985 ). All of these estimates are >10 times greater than the ordinary spontaneous lethal mutation rate (CROW and TEMIN 1964 ; MUKAI 1964 ). The common feature of all these studies is that the dysgenic crosses induce mostly lethal mutations and not mildly deleterious mutations. These lethal mutations are induced in the premeiotic germ line of the F₁ males in dysgenic crosses, which corresponds to the G-2 male in the extraction scheme (Figure 1) in the present study. Because most of these lethal mutations occur later in spermatogenesis, the mutated lethal chromosomes do not fix in the next generation (G-3) but rather segregate in the established lines (G-3) if mutation has occurred (SUH and MUKAI 1987 ), thereby reducing the viability of the line spuriously. Thus, the frequency of the lethal chromosome lines among the extracted second chromosomes is not strongly affected by the dysgenic effect at chromosome extraction, even if mutation occurred. This may be the reason why there is no difference in the lethal frequency and, hence, in the lethal load between the native and foreign strains; however, the segregating lethals in the established chromosome lines might manifest their effects as semilethal or severely detrimental chromosome lines, thereby reducing the average homozygote viability after excluding the lethal lines. This might be expressed as a slight inflation of the homozygous detrimental load in the foreign strain in the present study and in the male-originated lines in the 1970s study. The analyses of the Ishigakijima population (SUH and MUKAI 1991 ) show the same tendency, i.e., slight inflation of the detrimental load in the foreign genetic background and no difference in lethal load between the native and foreign genetic backgrounds. However, it can be concluded that the dysgenic effect at chromosome extraction would be very small, if any, and would not affect the viability estimate. Thus, the homozygous load and the genetic variances of the Raleigh natural populations of MUKAI and YAMAGUCHI 1974 and MUKAI et al. 1974 are not overestimated due to any artifact occurring at extraction of the chromosomes.

The change of genetic structure of the Raleigh population during 15 years: allele frequency in isozymes, frequencies of inversions, and effective population size:
The allelism rate of the lethal chromosomes was nearly constant over 15 years and, in addition, the frequencies of alleles at the enzyme loci and of the inversions had not changed. This suggests that the Raleigh natural population is a large panmictic population. The fact that most of these population genetic parameters did not change in 15 years in spite of the large difference in the homozygous load suggests that these enzyme loci and the loci that contribute to the homozygous load seem to segregate independently in the population, indicating that linkage equilibria have been maintained between the loci responsible for these electrophoretic variations and those that contribute to the homozygous load.

The unique inversion observed in this study is superimposed on In(2R)NS (KUSAKABE et al. 1990 ). This inversion is not due to a dysgenic effect during second chromosome extraction. STALKER 1976 has already reported the same unique inversion as In(2R)J. His sample of flies was collected in 1973 in Oklahoma. This inversion is presumably caused by P elements in natural populations, because the probe p25.1 hybridized at the breakpoints of the new rearrangement (KUSAKABE et al. 1990 ). This indicates that P elements already existed in the early 1970s or late 1960s and the inversion had been produced on In(2R)NS due to P-element activity and was maintained from the late 1960s to 1984 in the southern United States.

Potential mutator hypothesis and rapid invasion hypothesis:
The homozygous load had decreased in 15 years from 0.834 to 0.497, which is rather close to the value observed in Wisconsin in the early 1960s (0.404 in GREENBERG and CROW 1960 ; SIMMONS and CROW 1977 ). This decrease in homozygous load was due to both lethal and detrimental load components and, therefore, the load ratio did not change between these years. This suggests that MUKAI and YAMAGUCHI's study (1974) might be at the highest period for the homozygous viability load. An increase and then a decrease in the homozygous viability load in North America may support the rapid invasion hypothesis of P elements proposed by KIDWELL 1983 .

An increase and then a decrease in lethal frequencies were also observed both in the Katsunuma population in Japan (WATANABE et al. 1976B ) and in Korea (CHOO and LEE 1986 ) around 1970. MUKAI et al. 1985 reanalyzed the Katsunuma population in 1983 and compared the viability estimates with those of WATANABE et al. 1976B . Their quantitative analysis suggested that the model could explain an increase of lethal frequencies from 15 to 30% in 6–7 years in the Katsunuma population due to the rapid invasion of P elements. It is probable that the rapid invasion of transposable elements, such as P elements, had occurred in several areas around the world at these times, thereby inducing an increase of homozygous load in populations in the 1970s.

In this context, the potential mutator hypothesis proposed by CARDELLINO and MUKAI 1975 was prophetic. They accumulated spontaneous mutations on the second chromosome lines extracted from the Raleigh natural population and observed abnormally high rates of the lethal mutations and chromosomal aberrations. On the basis of these studies, CARDELLINO and MUKAI 1975 proposed the potential mutator hypothesis, which says that "about 70% of the second chromosomes in the natural population carry potential mutators which become actual mutators, perhaps when some kind of virus infects the flies... the present experimental materials might have been heavily infected by a virus in the course of the experiment or in the natural population. It was likely that viruses in bodies of the flies propagated rapidly in the laboratory conditions... This high frequency of chromosome and/or chromatid breaks should cause a large magnitude of genetic load... At present, we can only say that mutator factors produce a raw materials of evolution at a high expense of genetic load." We speculate that the large homozygous load observed in MUKAI and YAMAGUCHI 1974 might really be such an expense.

	FOOTNOTES

This article is dedicated to the memory of Dr. Terumi Mukai.
¹ Present address: Department of Biology, Faculty of Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan.
² Present address: Graduate School of Biological Sciences, Kyoto University, Kyoto 606-8224, Japan.
³ Present address: Toxicology Laboratory, Yokohama Research Ctr., Mitsubishi Chemical Corp., Yokohama, Kanagawa 227-8502, Japan.

	ACKNOWLEDGMENTS

We thank Cathy C. Laurie for sending us the flies used in these studies.

Manuscript received April 9, 1999; Accepted for publication October 7, 1999.

	LITERATURE CITED

TOP ABSTRACT MATERIALS AND METHODS RESULTS AND ANALYSES DISCUSSION LITERATURE CITED

CARDELLINO, R. A. and T. MUKAI, 1975  Mutator factors and genetic variance components of viability in Drosophila melanogaster.. Genetics 80:567-583[Abstract].

CHIGUSA, S. I., L. E. METTLER, and T. MUKAI, 1969  Characteristics of a southern population of Drosophila melanogaster.. Genetics 61:s10.

CHOO, J. K. and T. J. LEE, 1986  Genetic changes in a Korean population of Drosophila melanogaster.. Jpn. J. Genet. 61:337-343.

CROW, J. F. and R. G. TEMIN, 1964  Evidence for the partial dominance of recessive lethal genes in natural populations of Drosophila. Am. Nat. 98:21-33.

ENGELS, W. R., 1979  Hybrid dysgenesis in Drosophila melanogaster: rules of inheritance of female sterility. Genet. Res. 33:216-236.

ENGELS, W. R., 1997  Invasions of P elements. Genetics 145:11-15[Medline].

GREENBERG, R. and J. F. CROW, 1960  A comparison of the effect of lethal and detrimental chromosomes from Drosophila population. Genetics 45:1154-1168.

HALDANE, J. B. S., 1956  Estimation of viabilities. J. Genet. 54:294-296.

HIRAIZUMI, Y. and J. F. CROW, 1960  Heterozygous effects of viability, fertility, rate of development and longevity of Drosophila chromosomes that are lethal when homozygous. Genetics 45:1071-1083[Free Full Text].

IVES, P. T., 1950  The importance of mutation rate genes in evolution. Evolution 4:236-252.

KIDWELL, M. G., 1983  Evolution of hybrid dysgenesis determinants in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 80:1655-1659[Abstract/Free Full Text].

KIDWELL, M. G., J. F. KIDWELL, and M. NEI, 1973  A case of high rate of spontaneous mutations affecting viability in Drosophila. Genetics 75:133-153[Abstract/Free Full Text].

KIDWELL, M. G., J. F. KIDWELL, and J. A. SVED, 1977  Hybrid dysgenesis in Drosophila melanogaster: a syndrome of aberrant tracts including mutation, sterility and male recombination. Genetics 86:813-833[Abstract/Free Full Text].

KUSAKABE, S., K. HARADA, and T. MUKAI, 1990  The rare inversion with a P element at the breakpoint maintained in a natural population of Drosophila melanogaster.. Genetica 81:111-115.

MACKAY, T. F. C., 1987  Transposable element-induced polygenic mutations in Drosophila melanogaster.. Genet. Res. 49:225-233.

MUKAI, T., 1964  The genetic structure of natural populations of Drosophila melanogaster. I. Spontaneous mutation rate of polygenes controlling viability. Genetics 50:1-19[Free Full Text].

MUKAI, T. and S. NAGANO, 1983  The genetic structure of natural populations of Drosophila melanogaster. XIV. Excess of additive variance of viability. Genetics 105:115-134[Abstract/Free Full Text].

MUKAI, T. and R. A. VOELKER, 1977  The genetic structure of natural populations of Drosophila melanogaster. XIII. Further studies on linkage disequilibrium in a large population. Genetics 86:175-185[Abstract/Free Full Text].

MUKAI, T. and O. YAMAGUCHI, 1974  The genetic structure of natural populations of Drosophila melanogaster. XI. Genetic variability in a local population. Genetics 76:339-366[Abstract/Free Full Text].

MUKAI, T., L. M. METTLER, and S. I. CHIGUSA, 1971  Linkage disequilibrium in a local population of Drosophila melanogaster.. Proc. Natl. Acad. Sci. USA 68:1065-1069[Abstract/Free Full Text].

MUKAI, T., S. I. CHIGUSA, L. E. METTLER, and J. F. CROW, 1972  Mutation rate and dominance of genes affecting viability in Drosophila melanogaster.. Genetics 72:335-355[Abstract/Free Full Text].

MUKAI, T., T. K. WATANABE, and O. YAMAGUCHI, 1974  The genetic structure of natural populations of Drosophila melanogaster. XII. Linkage disequilibrium in a large local population. Genetics 77:771-793[Abstract/Free Full Text].

MUKAI, T., M. BABA, M. AKIYAMA, N. UOWAKI, and S. KUSAKABE et al., 1985  Rapid change in mutation rate in a local population of Drosophila melanogaster.. Proc. Natl. Acad. Sci. USA 82:7671-7675[Abstract/Free Full Text].

NEI, M., 1968  The frequency distribution of lethal chromosomes in finite populations. Proc. Natl. Acad. Sci. USA 60:517-524[Free Full Text].

PRAKASH, S., R. C. LEWONTIN, and J. L. HUBBY, 1969  A molecular approach to the study of genic heterozygosity in natural populations. IV. Patterns of genic variation in central, marginal and isolated populations of Drosophila pseudoobscura. Genetics 61:841-858[Free Full Text].

SHAW, C. R. and R. PRASAD, 1970  Starch gel electrophoresis of enzymes—a compilation of recipes. Biochem. Genet. 4:297-320[Medline].

SIMMONS, M. J. and J. F. CROW, 1977  Mutation affecting fitness in Drosophila population. Annu. Rev. Genet. 11:49-78[Medline].

SIMMONS, M. J. and J. K. LIM, 1980  Site specificity of mutations arising in dysgenic hybrids of Drosophila melanogaster.. Proc. Natl. Acad. Sci. USA 77:6042-6046[Abstract/Free Full Text].

STALKER, H. D., 1976  Chromosome studies in wild populations of D. melanogaster.. Genetics 82:323-347[Abstract/Free Full Text].

SUH, D. S. and T. MUKAI, 1987  Mosaic lethal mutations as one of the syndrome of hybrid dysgenesis due to the P element in Drosophila melanogaster.. Jpn. J. Genet. 62:51-58.

SUH, D. S. and T. MUKAI, 1991  The genetic structure of natural populations of Drosophila melanogaster. XXIV. Effects of hybrid dysgenesis on the components of genetic variance of viability. Genetics 127:545-552[Abstract].

TEMIN, R. G., H. U. MEYER, P. S. DAWSON, and J. F. CROW, 1969  The influence of epistasis on homozygous viability depression in Drosophila melanogaster.. Genetics 61:497-519[Free Full Text].

WALLACE, B., 1956  Studies on irradiated populations of Drosophila melanogaster.. J. Genet. 54:280-293.

WATANABE, T. K., O. YAMAGUCHI, and T. MUKAI, 1976a  The genetic variability of third chromosomes in a local population of Drosophila melanogaster.. Genetics 82:63-82[Abstract/Free Full Text].

WATANABE, T. K., T. WATANABE, and C. OHSHIMA, 1976b  Genetic changes in natural populations of Drosophila melanogaster.. Evolution 30:109-118.

YAMAGUCHI, O. and T. MUKAI, 1974  Variation of spontaneous occurrence rates of chromosomal aberrations in the second chromosomes of Drosophila melanogaster.. Genetics 78:1209-1221[Abstract/Free Full Text].

YAMAGUCHI, O., R. A. CARDELLINO, and T. MUKAI, 1976  High rates of occurrence of spontaneous chromosome aberrations in Drosophila melanogaster.. Genetics 83:409-422[Abstract/Free Full Text].

YUKUHIRO, K., K. HARADA, and T. MUKAI, 1985  Viability mutations induced by the P elements in Drosophila melanogaster.. Jpn. J. Genet. 60:531-537.

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