P S - I - 2C O N T R IBUTIONS OF DROSO P H I L A RESE A R C H TO

Q U A N T I T A T I V E GENETICS AND A N I M A L B R E E D I N G

C o n t r i b u c i S n de la investigacidn sobre Droso p h i l a a la g e n S t i c a cuantitativa y m e j o r a animal

R. FRANKHAM*

A U S TRALIA

Our knowledge of genetics comes primarily from discoveries made in laboratory species, especially D rosoph ila m s la n o g a s te r , and this is particularly true of quantitative genetics and animal breeding. The contributions of D ro so p h ila research to these fields were reviewed at the 1st Congress by HAMMOND (1974) and previous reviews are referred to by him. It is worth restating the three major roles for laboratory animals in breeding research recognised by ROBERTSON (1959), namely:(i) The experimental evaluation of theory(ii) Research into the genetic system underlying quantitative variation, and(iii) As physiological analogues to predict the consequences of selection on traits in commercial species.D ro so p h ila can fulfil the first two of these functions but other species are necessary to fulfil the third role.

Traditionally, D ro so p h ila has been used as a research organism for four main reasons,(a) Short generation interval and high fecundity(b) Low cost of culturing individuals(c) Easily studied polytene chromosomes(d) Range of available stocks and techniques (e.g. balancer chromosomes and deletion stocks) and body of accumulated knowledge. In the future the accumulated knowledge of the developmental genetics and molecular biology of D ro so p h ila will be of increasing importance to its role as a laboratory animal.

In an era when funding cuts have forced careful reviews of our priorities it is relevant to examine the contributions of D ro so p h ila research to quantitative genetics and animal breeding. The major contributions of D ro so p h ila research to these fields are listed in TABLE 1. To save space, only the most recent paper of those prior 1974 is referred to on each topic; It is clear that D ro so p h ila research has had a profound impact on our field. A common pattern has been for quantitative genetics theory to be evaluated first in D ro so p h ila , then in other laboratory species and finally in commercially important species. The important inputs at the second level are. outside my brief.

* School of Biological Sciences, Macquarie University, North Ryde, N.S.W. 2113, Australia.

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TABLE 1

CONTRIBUTIONS OF DROSOPHILA RESEARCH TO QUANTITATIVE GENETICS AND ANIMAL BREEDING.

Topic

1. Prediction of- shortterra response to selection

2. Effects of population size oh short term response to selection

3. Theory of limits in artificial selection (ROBERTSON, 1960)

4. Effects of populationsize bottlenecks on selection response (JAMES, 1971)

5. .Variation among replicate selection lines (HILL, 1974, 1977)

6. Two trait selectiontheory (HAZEL and LUSH, 1942)

7. Selection with sublining (WRIGHT, 1939;MADALENA and HILL, 1972)

8. Individual v family v combined selection (LUSH, 1947)

9. Inbreeding theory (WRIGHT, 1921)

10. Reciprocal recurrent selection(COMSTOCK Ot a l . , (1949)

11. Optimum selection intensities (ROBERTSON, 1970)

12. Asymmetrical responses to bidirectional selection due to a rare allele of large effect

13. Assortative mating and selection

14. Correlated response theory

15. Recombination and selection response

16. Foundation population(s)- one or several (JAMES, 1966)

17. Genetical basis of heterosis

18. An evaluation of methods for overcoming selection plateaux

19. Effects of intermittent versus continuous selection

20. Effects of X-rays on selection response

21. Genetical analyses of long term selection lines

22. Decline in fitness in selection lines

23. Genetic variation for characters exhibiting invariant phenotypes

24. Inbreeding effect of selection (ROBERTSON, 1961)

25. Nature of quantitative genetic variation

26. Contributions of mutations to selection response

27. Unequal crossing over as a source of genetic variation

28. Effects of two-trait selection on the genetic correlation

References

CLAYTON et a t. (1957b)FRANKKAM at a l. (1968a)OSARIO (1981)JONES at al. (1968)OSARIO (1981)

see HAMMOND (1973)FRANKHAM (1980b)

HAMMOND (1973)YUKSEL (1974)See SEN and ROBERTSON (1964)

KATZ and YOUNG (1975)MADALENA and ROBERTSON(If 75RATH!S’ and NICHOLAS (1§80)See McBRIDE and ROBERTSON

(1963)AVALOS and HILL (1981)See KIDWELL and KEMPTHORNE

(1966)RUMBALL (1978)See KOJIMA and KELLEHER

(1963)BROWN and BELL (1980)FRANKHAM (1977)

FRANKHAM and NURTHEN (1981)

McBRIDE and ROBERTSON (1963)

CLAYTON at al. (1957a)

McPHEE and ROBERTSON (1970) MARKOW (1975)THOMPSON (1977)HOWE and JAMES (1973)

ROBERTSON and REEVE (1955)

OSMAN and ROBERTSON (1968)

RATHIE and BARKER (1968)

See HOLLINGDALE and BARKER (1971b)

See FRANKHAM at a l. (1968b) YOO (1980b, 1980c)YOO at al. (1980)LATTER and ROBERTSON (1962)

See REJ4DEL (1967)

See JONES (1969)YOO (1980d)See PIPER (1971)See THOMPSON and THODAY

(1979)See HOLLINGDALE (1971) ROBERTSON (1978)FRANKHAM (1980a)YOO (1980b)FRANKHAM a t d l . (1978, 1980)

SHERIDAN and BARKER (1974)

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Clearly there may be danger of extrapolation from laboratory animals to commercially important species, as many authors have cautioned. However, I know of no case where the results obtained using Drosophila have been in conflict with results obtained for characters with similar spectra of genetic variation in other laboratory species or in commercially important species (see also BELL, 1974).

Five topics, where recent Drosophila research^as contributed to animal breeding have been chosen for more detailed discussion. Other important recent contributions not discussed in detail, are listed in TABLE 1.

1. THE CONTRIBUTIONS OF MUTATIONS TO SELECTION RESPONSE.

Significant contributions of "mutations" arising in long term selection lines to response in those lines have been found by MATHER and WIGAN (1942), HOLLINGDALE (1971), FRANKHAM &t at. (1978, 1980), FRANKHAM (1980a) and YOO (1980b). The soabrous allele has been found at high frequencies in abdominal bristle selection lines by several workers. HOLLINGDALE (1971), FRANKHAM (1980a) and YOO (1980b) showed that their sea alleles arose as mutations during the selection experiment, rather than being derived from their base populations. On the basis of the time of first detection of mutant horaozygotes, ROBERTSON (1978) inferred that 800. alleles detected in selection lines by other authors had also arisen as mutations in those lines. FRANKHAM (1980a) and YOO (1980b) presented evidence that high frequency lethal chromosomes in abdominal bristle selection lines had arisen by "mutation". These conclusions would be negated if these chromosomes contained synthetic lethals rather than single locus lethals but I have evidence to exclude this possibility. We have found a further "mutational" contribution to selection response for low abdominal bristle number in a near homozygous selection line due to the dominant mutant Hairless (FRANKHAM and STEWkRT, unpublished).

The above conclusions in relation to long-term selection response are in apparent conflict with the results of CLAYTON and ROBERTSON (1955, 1964) and HOLLINGDALE and BARKER (1971a) who found little contribution of mutations to short-term selection response. This conflict has been resolved by HILL (1982) in an excellent theoretical paper. He showed that the mutational contributions to selection response are generally minor for about 20 generations of selection but are likely to be of increasing importance beyond this time. It should be noted that the above results cast doubt on attempts to infer the nature of quantitative genetic variation in base populations from long term selection studies (see LATTER 1969; DUDLEY, 1977; COMSTOCK and ENFIELD, 1981) as mutational contributions to selection response have been assumed to be negligible.

The research with Droeophila referred to in this section would not have been possible without the special stocks and accumulated genetic knowledge available only in Droeophila.

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2. INDIVIDUAL, FAMILY AND COMBINED SELECTION

LUSH (1947) developed theory on the relative effectiveness of individual selection, family selection and on an index combining individual and family information (combined selection). He predicted that combined selection would be more effective than individual or family selection. The relative efficiency of individual versus family selection depended on the heritability, with individual selection being more effective at higher heritabilities and family selection yielding greater response for low heritability characters. Experimental evaluations of this theory have been inconclusive. CLAYTON e t a l .(1957b) and McBRIDE and ROBERTSON (1963) reported reasonable agreement between observed and expected selection responses for abdominal bristle number in Drosophila, in comparisons of individual, half-sib family and full-sib family selection and of individual selection with combined selection, respectively. The evaluations of this theory for egg production traits in poulty (KINNEY e t a l t , 1970; GARWOOD e t a l t , 1980} GARWOOD and LOWE, 1981) have not yielded significant, deviations from expectations, thouc i KINNEY e t a l t (1970) found, in contrast to expectations, that individual selection was more effective than family selection on a standardized basis. Similarly, evaluations of this theory for size characters in Tribo lium (WILSON, 1974; CAMPO and TAGARRO, 1977) did not yield significant deviations from expectations, but the trends in selection response of the treatments were not as expected from theory. The equivocal results in poultry and T rib o liu m may reflect real deviations from the theoretical expectations or they may simply be due to the difficulties of carrying out experiments sufficiently large to detect the often small differences expected.

AVALOS and HILL (1981) evaluated individual versus combined information for abdominal bristle number in D rosoph ila and obtained results in agreement with LUSH's theory. JAMES (pers. comm.) is carrying out a large scale comparison of individual, and combined selection for sternopleural bristle number in D rosophila t He obtained ratios of response to combined/individual selection of 133 ± 9.7% and 111 ± 4% in two replicated experiments of one and five generation, respectively, not significantly different from the expected ratio of 121%. None of the evaluations have given significant deviations from expectations, so the theory is, at least to my mind, adequate for characters exhibiting mainly additive genetic variation. This conclusion may not apply for characters affected by a congenitally transmitted pathogen with characteristics similar to those of the lymphoid leukosis virus in poultry (HARRIS, 1979).

3. LONG TERM SELECTION

The main impetus for the recent era of long term selection studies has been the availability of predictive theory, particularly ROBERTSON'S (1960) theory of limits in artificial selection. ROBERTSON'S (1960) theory has been evaluated by JONES e t a l t (1968), using abdominal bristle number in D rosophila , and EISEN (1975) using body weight in mice. In both experiments long term response for the selection treatments was in general agreement with expectations. OSARIO (1981) has extended this evaluation to characters with different spectra of

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genetic variation in his studies using thorax length and pupae number in D roeoph ila . For thorax length the results were comparable to those mentioned above and in general agreement with expectations. Conversely, results for pupae number were not in accord with expectations, but this was thought to be an artifact of complications in the culture conditions.

Long term selection studies have been reviewed by BARKER (1967), AL-MURRANI (1974), ENFIELD (1974, 1980), HAMMOND (1974) and KRESS (1975). Recently YOO and colleagues (YOO, 1980a, 1980b, 1980c, 1980d;YOO e t a l . , 1980) reported on an extensively replicated selection study for abdominal bristle number in D rosoph ila using large population sizes and of 86-89 generations duration. Response continued for at least 75 generations. Final means averaged over four times the initial mean; average total response was 16 phenotypic standard deviations, 36 additive genetic standard deviations and 51 times the first generation response. These probably represent the greatest responses achieved in any selection experiments to date. Each replicate showed its own characteristic pattern of selection response, total response and regression on relaxation of selection. Each line had unfixed favourable alleles at the termination of selection as all lines regressed on relaxation of selection. As referred to in section 1, there was evidence that lethal and visible mutations occurring in the lines made an important contribution to selection response. These studies confirm and extend the results of other long term selection studies in D roeoph ila and other laboratory and commercial species (reviewed in the above mentioned papers).

4. AUTOMATICALLY SCOREABLE QUANTITATIVE CHARACTERS.

The most serious impediment to quantitative genetics research is the cgst involved. The labour cost involved in scoring individuals for the quantitative character is the major expense for D roeophila workers. Consequently, systems for automatically scoring individuals for quantitative characters have been developed for geotaxis (HIRSCH, 1959), phototaxis (HADLER, 1964), escape behaviour (GRANT and METTLER, 1969), eclosion time (GRANT e t a l . , 1970; GRANT and HARRISON, 1970), body size (BAPTIST and ROBERTSON, 1976) and locomotor activity (MONTIJN a t a l , , 1974; VAN DIJKEN and SCHARLOO, 1979). Behaviourists often raise questions concerning what character is measured in such apparatus but these are not of particular relevance to quantitative geneticists. Successful selection- experiments have been done in all of the above systems. All have heritabilities of less than 20% and all are typically influenced by a wide range of environmental effects (see GROSSFIELD, 1978). Genetically marked stocks can be run as internal controls with the selection lines in most of the above systems to obviate environmental trends. Scoring of phototaxis is semi-automatic in the countercurrent distribution apparatus (BENZER, 1967; TOMPKINS e t a l . , 1978). ELENS (1972) selected successfully for phototaxis using this apparatus but realized heritabilities and other details were not presented. Further labour savings can be made by using the cold shock desperming technique (NOVITSKI and RUSH, 1949) rather than collecting virgins in the usual way.

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The above devices have not come into general usage in quantitative genetics (however, see MARROW, 1975 and THOMPSON, 1977) but they deserve careful consideration for studies where large population sizes, extensive replication or intense selection are desired. The locometer (VAN DIJKEN and SCHARLOO, 1979) is particularly impressive due to the short duration of runs (15-20 minutes) and the ability to handle 13 groups of 100 flies simultaneously.

Most of these devices have measurement limits. Consequently, the automatically scoreable characters seem most suitable for research into the nature of quantitative genetic variation and for short term selection studies where the measurement limits are unlikely to be a problem.

5. PARENTAL AGE AND HERITABILITYBEARDMORE, e t a l . (1975) and BEARDMORE and SHAMI (1976) reported

that heritabilities for sternopleural bristle number in D rosophila me la n o g a ste r and for fin ray number in the Guppy P o e o il ia r e t ic u la ta changed with parental age. Both these characters do not change after "birth" so the observations are different from those reported for characters which change during adult life. These findings challenge our understanding of quantitative genetics and, if widespread, would lead to changes in the emphasis on short generation intervals in animal breeding. Attempts to repeat the D rosophila experiments have met with variable success. BEARDMORE and SHAMI (1976) reported that LOPEZ-FANJUL had obtained similar results using the Vallecas strain of D rosoph ila , but, LOPEZ-FANJUL’s results were, in fact, unclear and somewhat contradictory. ANGUS (1979) reported higher realized heritabilities for older versus younger parents for the Votanikos strain used by BEARDMORE e t a l . (1975). Conversely, ROBERTSON (pers. comm., 1976) failed to find an effect of parental age on heritability for sternopleural bristle number in the Dahomey strain. CALXGARI and BABAN (1981) found parental age effects on the same character in an inbred line. However, they showed that this effect was an artifact due to an effect of parental age on number of progeny produced. Several attempts in my laboratory to repeat the BEARDMORE e t a l . (1975) findings using Australian strains of D rosophila or their Votanikos strain have failed to demonstrate convincing effects of parental age on heritability of sternopleural bristle number. Consequently, effects of parental age on heritability are probably not a general phenomenon, and the existence of a genetic effect remains an enigma.

PROBLEMS REQUIRING RESEARCH.

The following are problems I would identify as requiring research:1. M u l t i - t r a i t s e le c t io n Practical breeders express disquiet concerning multi-trait selection theory. This is mainly due to either poor response to selection, or to calculated index weights having the wrong sign. At least part of the problem seems to be due to non­positive definite matrices (HILL and THOMPSON, 1978) (this corresponds to heritabilities outside the 0-1 limits or genetic correlations outside the -1 to +1 limits). Large scale replicated evaluations of multi-trait selection theory are required to test the adequacy of the theory.

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2. M ethods f o r im proving h e te r o t io t r a i t s Many commercial animal products come from crossbreds. In spite of considerable research, particularly by BELL and colleagues (see BROWN and BELL, 1980), there seems to be no consensus as to the most efficient procedures for improving heterotic traits. In particular, it is unclear what the best procedures are for improving egg production stocks in poultry and within line selection, reciprocal recurrent selection and inbreeding and hybridization have been used by different breeding companies.3. n a tu re o f q u a n t i ta t iv e g en e tio v a r ia t io n Many of the parameters we require to optimise selection procedures, especially for long term selection are unknown. Such parameters as the number of segregating loci, number of alleles per locus and the allelic frequencies and allelic effects distribution responsible for the genetic variation for quantitative characters are unknown but are necessary to predict the limits to artificial selection.4. D ecline i n re p ro d u c tiv e f i t n e s s in s e le c t io n l in e s Decline in reproductive fitness in selection lines is widely observed but is not quantitatively predictable. This problem has received much less attention than its practical importance would dictate. The lack of predictive theory seems to be an impediment to research on this problem.

THE FUTURE

Clearly research with D rosophila and other laboratory animals has led to great advances in quantitative genetics and animal breeding.There can be little doubt that D rosophila will continue to be the first species on which evaluations of new theory are reported. Hopefully, much of this work will be done using automatically scoreable characters to encourage extensive replication at minimal costs. There has been a much needed move towards studies of the physiology and biochemistry of quantitative character differences and selection response (see FALCONER e t a l . , 1981 for a particularly elegant example). This research will not be" done in D rosoph ila , but must be done using the species involved or their physiological analogues. With molecular probes becoming commonplace, the power of genetic analyses in commercially important species is rapidly increasing. Unless considerable progress is made in delimiting genes with favourable effects on quantitative characters in commercially important species we may be faced with the reality of genetic engineering before we have defined genes we wish to engineer. Despite the above trends, several types of research will remain the preserve of laboratory animal workers. Long term selection work must remain largely restricted to laboratory animals (particularly D rosophila) due to constraints of generation interval and costs.Research on the nature of quantitative genetic variation is likely to remain largely the preserve of D rosophila research as it is only in D rosophila that we have the required techniques for genetic analysis and the necessary background information on genetics, cytogenetics, developmental biology and molecular biology.

The proportion of quantitative genetics research done using D rosoph ila has declined in recent years. In spite of this, the contributions from D rosoph ila research have been substantial and many of the findings could not have been made with any other species. To take full advantage of D rosoph ila as a research organism we must analyse

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problems and peculiarities with all the tools at our disposal for in no other organism do we have such powers of genetic analysis. It must be emphasised that we are in a state of ignorance concerning the genetics of quantitative genetic variation. For no quantitative character do we kncxy the number of loci, number of alleles per locus, allelic effects - allelic frequencies distribution, gene interaction effects and linkage relations responsible for the observed genetic variation, let alone the biochemical and developmental effects of the loci and the patterns of gene regulation. It is only in Drosophila that we can hope to have such information. The unexpected discoveries of split genes and mobile genetic elements by molecular biologists should serve to remind us that we may have surprises awaiting us.

SUMMARY

Contribution of D r o s o p h i l a research to quantitative genetics and animal breeding research are tabulated and recent results on the contribution of mutations to selection response, on individual, family and combined selection, on long term selection, on automatic ally- scoreable quantitative characters and on parenteral age and - heritability, are reviewed. Problems requiring research are document ed. In spite of trends for more research to be done on commercial species or their physiological models, D r o s o p h i l a seems likely to rethin a crucial role as a model organism for quantitative genetic and animal breeding research, especially for evaluating new theory, for long term selection studies and for research into the nature of quantitative genetic variation. The need to utilise methods of genetig analyses, available only in D r o s o p h i l a , is stressed.

RESUMEN

Se tabulan las contribuciones de la investigaciSn con D r o s o ­p h i l a para la investigaciSn genStica cuantitativa y de mejora ani­mal, y se examinan los tiltimos resultados sobre las contribuciones de las mutaciones a la respuesta de selecciSn a largo plazo, los - carScteres cuantitativamente clasificables y la edad a la reproduc- ci6n y herabilidad. Se expone documentaciSn sobre lps problemas ne- cesitados de investigaciSn. Pese a las tendencias de que se realice mSs investigaciSn sobre las especies comerciales o sus modelop fi- siol6gicos, parece probable que la D r o s o p h i l a siga desempefiando un papel crucial como organismo modelo para la investigaciSn genStica cuantitativa y de crla animal, sobre todo para la valoraciSri de nue vas teorlas, para lbs estudlos de selecciSn a largo plazo y la in­vestigaciSn de la naturaleza de la variaciSn genStica cuantitativa.Se acenttia la necesidad de utilizar mStodos de anSlisis genStico, so lamente practicables en la D r o s o p h i l a .

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BEARDMORE, J.A. and SHAMI, S.A. (1976): Parental age, genetic variationand selection, in: P opula tion G enetics and Ecology (Eds. s . Karlin and E. Nevo) pp. 3-22. Academic Press: New York.

bell, a .e . (1974): G enetic m odelling w ith labora tory anim als:In tro d u c tio n . Proc. 1st. World Cong. Genetics Applied to Livestock Production. 1:413-424.

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BROWN, W.P. and BELL, A.E. (1980): An experimental comparison ofselection alternatives to plateaued response. G en etic s, 94:477- 496.

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CAMPO, J.L. and TAGARRO, P. (1977): Comparison of three selectionmethods for pupal weight of T rib o liim eastaneum. Arm. G enet. S e l . A nim ., 9:259-268.

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