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Genetics, Vol. 169, 671-682, February 2005, Copyright © 2005
doi:10.1534/genetics.104.033274
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Department of Biology, University of Rochester, Rochester, New York 14627
1 Corresponding author: Department of Biology, University of Rochester, Rochester, NY 14627.
E-mail: aorr{at}mail.rochester.edu
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ABSTRACT |
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 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSLITERATURE CITED |
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Mutations that cause meiotic drive distort Mendelian ratios to their own advantage, usually by inactivating sperm that carry a homologous chromosome. X chromosome-bearing sperm might, for instance, inactivate Y chromosome-bearing sperm. While obviously advantageous for the driving mutation, meiotic drive imposes a fertility cost on its bearers (since many gametes are rendered nonfunctional) as well as a fitness cost on most other genes in the genome (LYTTLE 1991). When residing on the sex chromosomes, mutations causing meiotic drive also bias sex ratios away from the 50:50 favored by Fisherian selection. For all these reasons, there will usually be strong selection to suppress meiotic drive (SANDLER and NOVITSKI 1957; LYTTLE 1991; JAENIKE 2001).
It is easy to imagine how mutations causing meiotic drive could ultimately give rise to intrinsic postzygotic isolation between taxa: two allopatric populations might each be invaded by different meiotic drive mutations; if each mutation later becomes suppressed, both populations will return to normal segregation ratios; if, however, these populations later come into secondary geographic contact and hybridize, this normally cryptic meiotic drive could become reexpressed (assuming that the suppressors of meiotic drive are less than fully dominant). In the simplest (although not the only) scenario, X-linked drive alleles might inactivate Y-bearing sperm in hybrids, while Y-linked alleles would inactivate X-bearing sperm, rendering XY hybrids sterile. Such a scenario might even help to explain "Haldane's rule," the preferential sterility or inviability of hybrids of the heterogametic (XY) sex, an idea that was proposed independently by FRANK (1991) and HURST and POMIANKOWSKI (1991).
TAO and HARTL (2003), HENIKOFF et al. (2001), and HENIKOFF and MALIK (2002) have recently suggested variations on the meiotic drive theory of postzygotic isolation. In Tao and Hartl's scenario, struggles over sex ratio are especially acute in the heterogametic sex as different portions of the genome in heterogametic individuals "prefer" different sex ratios (the Y chromosome in Drosophila, for instance, prefers more sons). In Henikoff and colleagues' scenario, struggles over which chromosome segregates into an egg (and not into a polar body) in female meiosis give rise to bouts of meiotic drive followed by suppression of drive; these bouts, they suggest, involve evolution at centromeric sequences and at the special histones that bind these sequences. Despite their differences, these models all share a central theme: segregation distorters appear and are then suppressed within species, only to be reexpressed in species hybrids.
Although the meiotic drive theory of postzygotic isolation is attractive—especially as segregation distortion occurs in a wide variety of organisms, including insects, mammals, plants, and fungi (LYTTLE 1991)—it fell out of favor in the early 1990s. The main reason was that experiments by COYNE (1986), JOHNSON and WU (1992), and COYNE and ORR (1993) found no segregation distortion in hybrids between several pairs of Drosophila species. (These hybridizations produce partially fertile F1 hybrids, allowing tests of segregation distortion in hybrid gametogenesis.) These findings were widely viewed as fatal to the meiotic drive theory of speciation (a view once shared by the senior author).
More recent studies, however, suggest that Coyne, Orr, Johnson, and Wu may have been unlucky in their choice of species pairs or of hybrid genotypes. Several cases of normally cryptic segregation distortion have now been described. All occur in Drosophila, presumably reflecting the intense genetic scrutiny of this genus. By far the best studied of these cases involves the species pair Drosophila simulans and D. mauritiana. TAO et al. (2001) showed that otherwise D. simulans males that are homozygous for a small region of the D. mauritiana third chromosome suffer sex ratio segregation distortion, producing 
80% daughters. Tao et al. suggest that the D. simulans genome carries an X-linked meiotic drive factor(s) that is normally suppressed within species by a dominant autosomal suppressor on the D. simulans third chromosome. When this dominant suppressor is replaced by recessive autosomal material from D. mauritiana, sex chromosome meiotic drive results. TAO et al. (2001) map this autosomal suppressor to <80 kb of DNA; they call the putative suppressor gene residing in this region too much yin (tmy). Similarly, DERMITZAKIS et al. (2000) showed that certain hybrid introgression lines between D. simulans and D. sechellia suffer male meiotic drive, which causes sex ratio distortion among their progeny. Although several different introgression lines show such distortion, complementation tests suggested that the same autosomal region is involved in all lines (DERMITZAKIS et al. 2000). While the above cases involve hybrids between named "good" species, other cases involve hybrids between populations or strains within species. In one, D. simulans flies produced by crossing individuals from Tunisia with individuals from Seychelles or New Caledonia suffer meiotic drive, while pure-population individuals do not (MERCOT et al. 1995; CAZEMAJOR et al. 1997; MONTCHAMP-MOREAU and JOLY 1997). In another, hybrids between certain stocks of D. subobscura suffer meiotic drive, while pure-stock individuals do not (HAUSCHTECK-JUNGEN 1990).
Here we report the discovery of segregation distortion in hybrids between the Bogota and USA subspecies of D. pseudoobscura, taxa that have often been viewed as paradigmatic of the earliest stages of speciation (e.g., LEWONTIN 1974). The Bogota subspecies is restricted to high elevations near Bogota, Colombia and is geographically isolated from the USA subspecies of North and Central America by >2000 km (PRAKASH 1972). The Bogota-USA system represents an especially young hybridization: DNA sequence analysis shows that the Bogota and USA subspecies may have separated as recently as 155,000–230,000 years ago (SCHAEFFER and MILLER 1991; WANG et al. 1997; MACHADO et al. 2002; MACHADO and HEY 2003). Not surprisingly, the Bogota and USA subspecies are incompletely reproductively isolated: they show little or no prezygotic isolation (PRAKASH 1972) or conspecific sperm precedence (DIXON et al. 2003) and produce completely fertile female hybrids. Male hybrids are also fertile in one direction of the hybridization (USA mothers), while male hybrids from the reciprocal direction of the hybridization (Bogota mothers) have traditionally been described as completely sterile. This hybrid male sterility has been the subject of several genetic studies (PRAKASH 1972; DOBZHANSKY 1974; ORR 1989a,b; ORR and IRVING 2001).
Here we show that hybrid males having Bogota mothers are not, in fact, completely sterile; instead these hybrids become weakly fertile when aged. Surprisingly, these F1 hybrid males produce almost all daughters. The results presented below suggest that this sex ratio distortion reflects normally cryptic segregation distortion in hybrid males. We also present the results of a preliminary genetic analysis of this distortion.
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MATERIALS AND METHODS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSLITERATURE CITED |
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Male fertility:
Male fertility was measured by assessing sperm motility, which is standard in studies of hybrid male sterility in Drosophila (e.g., COYNE 1985; VIGNEAULT and ZOUROS 1986; ORR 1987; ORR and COYNE 1989; DAVIS and WU 1996). Testes were dissected from 4- day-old virgin males and examined under a compound microscope with dark field optics. Males were classified into three sperm motility classes: Many, wherein a male had a large number of motile sperm that filled the field of vision; Few, wherein small pockets of motile sperm were seen; and None, wherein no motile sperm were seen. While sperm motility is not equivalent to fertility, the two are strongly correlated (ORR 1987). In one large cross described below, male fertility was measured by counting number of offspring produced, as these offspring were produced for other reasons.
Egg to adult lethality:
The frequency of lethality among offspring of hybrid males was measured by aging hybrid F1 males for 8–9 days and then single-pair mating them to 3- to 4-day-old virgin Bogota females. When a pair of flies began to produce first instar larvae, the pair was transferred to an egg-counting vial. This vial contained a small plastic spoon filled with standard media dyed purple to ease visualization of eggs. The adult pair was left in this vial for 24 hr and then transferred to a new egg-counting vial for another 24 hr. Because hybrid males are almost completely sterile, almost all eggs are unfertilized. It is thus impractical to measure hatch rates among the very rare fertilized eggs. Instead, we simply counted the number of dead offspring. In particular, each egg-counting vial was scored for number of dead eggs and dead first instar larvae 24 and 48 hr after the parents were removed. (Dead eggs and larvae of D. pseudoobscura are necrotic and unmistakably brown.) The media from the egg-counting vials were transferred to fresh vials and maintained at room temperature. Vials were scored for further larval lethality 7 days after the parental pair was removed. Vials were later scored for number of emerging adults. After 3 consecutive days in which no adults emerged, pupae were scored for lethality. (Empty pupal cases are easily distinguished from those containing a dead individual.) Pupal cases containing dead individuals were dissected to score sex; this is typically possible as D. pseudoobscura males have bright orange testes.
Statistics:
When comparing sex ratios produced by males of different genotypes, we treat each father as a single data point; i.e., each father produces a percentage of daughters. This is much more conservative than treating each offspring as a single data point. The null hypothesis of no difference in sex ratio between genotypes was tested with unpaired t-statistics on arcsin square-root transformed proportion daughters (SOKAL and ROHLF 1981). Nonparametric tests (Mann-Whitney U-test) on untransformed proportions usually yielded similar results. In our large X chromosome mapping experiments, the effect of chromosome regions on sex ratio was tested by comparing the sex ratios produced by all fathers that differ at a marker; only fathers producing 10 or more offspring were included in these mapping experiments, to ensure some accuracy in sex ratio measurements.
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RESULTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSLITERATURE CITED |
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The sex ratio among adult F1 hybrids was close to even, although there was a slight excess of females (mean ± SD, 55.1 ± 4.6%; Figure 1), suggesting mild hybrid male inviability in the F1 generation. Surprisingly, however, 18 of 97 lines produced some F2 hybrids. These cases did not reflect contamination as, in all instances, crosses were extremely difficult and very few F2 hybrids appeared (sometimes only a single fly). Several USA iso-female lines that produced F2 hybrids were retested; most consistently produced a few F2 offspring (results not shown). As the "Flagstaff-5" iso-female line produced the largest number of F2 hybrids, this line was divided into sublines and each subline was tested further. We chose the subline that produced the most F2 hybrids for further analysis. (The number of F2 hybrids produced by this subline varied with the Bogota stock to which it was crossed. In the best case, an average of 1.7 F2 progeny were produced per F1 male; in the worst case, an average of 0.02 F2 progeny were produced per F1 male; see below and some results not shown.) As the results presented below suggest that this subline carries a Mendelizing hybrid fertility rescue mutation, we refer to this stock as Hybrid male fertile (Hmf).
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We crossed hybrid F1 males carrying Hmf to many different genotypes of D. pseudoobscura females. The results are shown in Table 1. Remarkably, these normally sterile hybrid F1 males produce almost all daughters (88–99%). This is true regardless of the Bogota strain to which Hmf was initially crossed and regardless of whether the resulting F1 males were subsequently crossed to pure USA females, to pure Bogota females, or to hybrid F1 females (having USA or Bogota cytoplasm). The reciprocal class of Hmf F1 males—those having a USA mother—do not produce distorted sex ratios. Instead, these normally fertile F1 males produce offspring having nearly even sex ratios (Table 2).
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There are at least three possibilities. First, sex transformation may occur among the progeny of hybrid males, with genetic males transformed into somatic females. Second, hybrid inviability may occur among the progeny of F1 males, with most sons dying. Third, segregation distortion may occur in F1 males, such that most zygotes derive from sperm that carry an X chromosome. The sex transformation hypothesis is more plausible than it might first seem: partial or complete sex transformation has been observed in species hybrids both in Drosophila (STURTEVANT 1946) and in Caenorhabditis (BAIRD 2002). We were, however, able to rule out this possibility by using X-linked visible markers: we crossed Hmf-rescued hybrid F1 males to USA females carrying the X-linked mutation, yellow (1-74.5). As expected, almost all offspring were again female (Table 1, line 5). These daughters were all phenotypically y+, while the few emerging sons were phenotypically y. Sex transformation does not, therefore, occur among the offspring of F1 males.
We tried to distinguish the hybrid inviability and segregation distortion hypotheses in two ways. The first was indirect: with hybrid inviability, we expect the fitness of the sons of F1 males to depend on their genotype, e.g., on whether sons carry a Bogota or a USA X chromosome. As emphasized, however, F1 males produce almost all daughters regardless of whether F1 males are crossed to pure Bogota, pure USA, or hybrid females—and so regardless of whether their sons carry a pure Bogota X, a pure USA X, or a recombinant X chromosome. This pattern differs qualitatively from that expected with hybrid inviability.
The second approach was more direct: if the absence of sons reflects hybrid inviability, massive lethality must occur among the offspring of hybrid F1 males. To assess this, we measured egg, larval, and pupal lethality in a large cross involving hybrid F1 males, as described in MATERIALS AND METHODS and in Table 7. Once again, we found that hybrid F1 males produced almost all daughters (485 females, 29 males; Table 7). Not surprisingly, some lethality was seen in this cross (which does, after all, involve subspecific hybridization). The observed lethality was, however, far too rare to explain the near-absence of sons. Although 456 sons are "missing" (485 – 29 = 456), we observed very few dead embryos or larvae and only 37 dead pupae (Table 7). Importantly, we could score the sex of 21 of these dead pupae and almost all were female (17 females, 4 males). Sex ratio distortion thus appears before the pupal stage, but there is very little embryonic or larval lethality (Table 7).
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Genetic basis of hybrid segregation distortion—X chromosome mapping:
We would like to understand the genetic basis of hybrid segregation distortion. Given, however, that even "fertility-rescued" hybrid males remain highly sterile, all genetic analyses proved extraordinarily difficult and our sample sizes were, consequently, often less than ideal. Nonetheless, we were able to establish several facts, which we describe for the remainder of this article.
Given that hybrid segregation distortion occurs in F1 males that carry a Bogota X and a USA Y and that almost all daughters result, it seems likely that the Bogota X chromosome carries gene(s) that cause segregation distortion. To confirm this and to roughly map these putative X-linked genes, we produced backcross hybrid males that carried recombinant X chromosomes, a USA Y chromosome, and mostly USA autosomes. In particular, we backcrossed F1 females from the cross of Bogota Toro-1 females x USA ct (1-22.5) sd (1-43.0) y (1-74.5) se (1-156.5) males to USA Hmf males. Recombinant backcross males of known X chromosome genotype were then singly mated to wild-type Bogota Toro-1 females and the sex ratio of the resulting progeny was scored. The results are shown in Figure 2, which is arranged to match Figure 2 of ORR and IRVING (2001).
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The X-linked genes causing segregation distortion also show strong conspecific epistasis: comparisons among genotypes 1–4 and 9 reveal that no single X chromosome region from Bogota has any effect on sex ratio by itself. Instead, sex ratio distortion appears only when several X chromosome regions from Bogota are jointly introgressed into a USA background. It also appears that at least one gene causing segregation distortion is loosely linked to our X-linked markers, since the most Bogota-like of our backcross genotypes (ct+ sd+ y+ se+; genotype 16) does not suffer full F1-male-like levels of segregation distortion.
Hybrid segregation distortion and hybrid male sterility:
Although crude, the above mapping results resemble those from our previous work on hybrid male sterility between the Bogota and USA subspecies (ORR and IRVING 2001). Indeed the same regions of the Bogota X chromosome are involved in both hybrid male sterility and hybrid segregation distortion and these regions show a similar pattern of complex conspecific epistasis for both phenotypes. Moreover, the region near se plays a large—and necessary—role in both hybrid segregation distortion and hybrid male sterility. Our findings are, then, at least consistent with the idea that the same genes cause both phenomena. Indeed throughout many of the above crosses we noticed that hybrid males that show segregation distortion produce few progeny, while males that do not show segregation distortion produce many progeny.
To better assess this possible association between hybrid segregation distortion and hybrid male sterility, we scored the number of offspring produced by each recombinant backcross male from the above X chromosome mapping experiment. The results are shown in Figure 3. There is a highly significant correlation between sex ratio among progeny and the number of offspring produced by a male (r = –0.472, P < 0.0001; Kendall's 
= –0.297, P < 0.0001). This negative correlation is not an artifact of any inviability of sons, as sex ratio and number of daughters produced by a hybrid male are also strongly correlated (r = –0.372, P < 0.0001; Kendall's = –0.205, P < 0.0001). Although the evidence presented in this section certainly does not prove that the same genes cause both hybrid segregation distortion and hybrid male sterility, we cannot exclude this possibility.
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The existence of Bogota suppressors of segregation distortion is confirmed in the top panel of Figure 4. Genotypes A and B both carry an unrecombined X chromosome from Bogota as well as pure Bogota cytoplasm. But genotype A carries a Y chromosome from USA and only half of its autosomes from Bogota and shows strong segregation distortion; genotype B, on the other hand, carries a Y chromosome from Bogota and three-fourths of its autosomes (on average) from Bogota and shows little segregation distortion (t = 4.58, P < 0.0001). Replacing the Y chromosome and/or autosomes from USA with those from Bogota thus suppresses distortion. The middle panel of Figure 4 confirms that at least some of the suppressors of segregation distortion reside on the Bogota autosomes. Genotypes C and D both carry an unrecombined X chromosome from Bogota and a Y chromosome from USA; they differ only in the fraction of the autosomes that, on average, derive from Bogota (one-half in genotype C and three-fourths in genotype D). Genotype C shows strong segregation distortion, while genotype D shows weaker distortion (although this difference has borderline significance: t = 1.92, P = 0.065). While this contrast involved the Hmf stock, the bottom panel in Figure 4 shows that these findings do not depend on Hmf. Instead, hybrid males that carry fewer autosomes from Bogota (genotype E) show significantly stronger segregation distortion than do those that carry more autosomes from Bogota (genotype F), even when Hmf is not used (t = 2.63, P = 0.015).
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60% females). While the top half of Table 8 involves Hmf, the bottom half does not. In both cases, the autosomes affect the strength of hybrid segregation distortion.
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Genetic basis of hybrid segregation distortion—Y chromosome:
It appears that segregation distortion is strongest when hybrid males carry a USA Y chromosome. We performed a number of crosses that were essentially identical to many described above but in which hybrid males carried a Bogota Y chromosome. In all cases, we observed little sex ratio distortion among offspring. One example is shown in Figure 5. The backcross males shown there are similar to those shown in Figure 2. The key difference is that the males in Figure 2 carry a USA Y chromosome (and show strong sex ratio distortion), while the males in Figure 5 carry a Bogota Y chromosome (and show little sex ratio distortion; indeed all sex ratios are within 7% of each other). It is especially interesting to note that males having a Bogota-like X chromosome genotype (ct+ sd+ y+ se+) produce 65% daughters when carrying a Bogota Y chromosome (Figure 5); the same genotype produces 85% daughters when carrying a USA Y chromosome (Figure 2). Thus while some segregation distortion may occur on a Bogota Y genetic background, it is weaker than that on a USA Y background.
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To test this, we asked whether the SR chromosome causes segregation distortion on a largely Bogota genetic background, i.e., on a background that contains some suppressors of hybrid segregation distortion. In particular, we crossed USA SR females to Bogota Toro-1 males; the resulting F1 males carry an SR X chromosome, but a Y chromosome and haploid complement of autosomes from Bogota. As a control, we crossed USA SR females to USA Standard arrangement males; the resulting F1 males carry an SR X chromosome on an entirely USA genetic background. As expected, SR causes strong segregation distortion in control USA F1 males: scoring offspring from 52 F1 fathers (singly mated to USA Standard females), the average sex ratio was 96.5% daughters. The experimental hybrid F1 males also showed segregation distortion, although not as strong: scoring offspring from 75 F1 fathers (singly mated to USA Standard females), the average sex ratio was 87.4% daughters. While highly significant (t = 7.26, P < 0.0001), this difference is small and SR segregation distortion clearly still occurs in hybrid males. We also attempted to produce backcross hybrid males that carry an SR X chromosome on a homozygous autosomal Bogota background. Unfortunately, these crosses proved extremely difficult and we could not recover progeny from a meaningful number of SR backcross males.
It thus appears that SR may be slightly less effective on a Bogota genetic background. However, SR still causes strong segregation distortion when paired with a Bogota Y chromosome, unlike the X-linked hybrid segregation distortion genes described above. The hybrid and SR meiotic drive systems thus appear mostly independent.
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DISCUSSION |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSLITERATURE CITED |
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Our second main conclusion is that Bogota-USA hybrid males show segregation distortion. More precisely, Bogota-USA hybrid males having Bogota mothers produce almost all daughters (typically >90%). Several lines of evidence suggest that this sex ratio bias is caused not by male inviability or sex transformation, but by sex chromosome segregation distortion. This distortion occurs in crosses between all Bogota and USA strains tested. Reciprocal F1 hybrid males (those that have a USA mother and are highly fertile) do not produce distorted sex ratios. It is important to note that this case of hybrid segregation distortion, unlike those recently described in the D. simulans clade (e.g., TAO et al. 2001), affects not only later-generation hybrids but also F1 hybrids.
We do not yet know the precise functional basis of hybrid segregation distortion. The possibilities include "classic" meiotic drive in which X-bearing sperm inactivate Y-bearing sperm, which are not transferred to females (LYTTLE 1991); failure of Y-bearing sperm to function properly in the female reproductive tract (e.g., failure to migrate to sperm storage organs); or failure of Y-bearing male pronuclei to fuse with X-bearing female pronuclei following fertilization (yielding eggs that suffer no obvious necrosis, etc.). We currently know only that hybrid males produce few necrotic eggs or dead larvae; that sex ratio distortion appears before the pupal stage; and that hybrid segregation distortion is largely independent of the meiotic drive caused by the Sex Ratio (SR) X chromosomal arrangement. Because F1 hybrid males are highly sterile—and show disrupted spermatogenesis—our preliminary work suggests that cytological approaches alone will not cleanly resolve the functional basis of segregation distortion. We are thus planning real-time PCR analyses to characterize the stage at which sex chromosome segregation distortion first appears (e.g., in hybrid males vs. in the uterus of females immediately after copulation vs. in sperm storage organs several hours after copulation).
There are at least two possible interpretations of the present—and other—cases of normally cryptic hybrid segregation distortion. The first is that described in the Introduction: a mutation causing segregation distortion appears within one of the parental taxa, is subsequently suppressed, and becomes reexpressed upon hybridization of two taxa. The second is that segregation distortion never appeared in the evolutionary histories of either lineage leading to the present species and instead represents a hybrid pathology (DERMITZAKIS et al. 2000; ORR and PRESGRAVES 2000). Under this second interpretation, hybrid segregation distortion is a consequence of the inappropriate interaction of genes from two taxa and represents a special case of Dobzhansky-Muller incompatibilities between taxa (ORR 1995b). Unfortunately, we currently know of no way to distinguish between these possibilities.
We also report the results of a preliminary genetic analysis of Bogota-USA hybrid segregation distortion. Although the near-complete sterility of hybrid males showing segregation distortion obviously compromises any such analysis, several facts seem reasonably clear. For one thing, segregation distortion requires genes from several regions of the Bogota X chromosome. Also, the effect of these genes is suppressed within the Bogota subspecies by (incompletely dominant) autosomal alleles (we have not yet succeeded in localizing these autosomal genes). Moreover, segregation distortion is more extreme when the Bogota X chromosome is paired with a USA Y chromosome than with a Bogota Y chromosome.
These mapping experiments lead to our third and final main conclusion: the genetic basis of segregation distortion in the Bogota-USA hybridization is similar to that of hybrid male sterility between the same taxa. Our experiments confirm that the genes causing both phenomena map to the same regions of the X chromosome. More remarkably, both hybrid phenotypes show the same pattern of conspecific epistasis: both hybrid male segregation distortion and hybrid male sterility appear only when hybrids carry the appropriate combination of X-linked alleles from the Bogota subspecies, and no single X-linked region can, by itself, cause any hybrid segregation distortion or hybrid sterility (ORR and IRVING 2001). Moreover, one or more genes tightly linked to sepia play a large and necessary role in both phenomena. Our results also show a strong correlation between the fertility of individual backcross hybrid males and the sex ratio of their offspring. (The fact that this correlation is imperfect is not surprising, as individual males often produced very few offspring, causing sex ratio to be measured with considerable error.)
Although these findings are suggestive, we do not claim that hybrid segregation distortion causes Bogota-USA hybrid male sterility. Indeed there are some reasons for thinking that segregation distortion cannot be the sole cause of hybrid male sterility. For one thing, the segregation distortion discovered here—if involving classic meiotic drive—would inactivate only half of all sperm (i.e., those carrying a Y chromosome), which could not explain the near-complete sterility of F1 males having a Bogota mother. Although additional meiotic drive systems might act within Bogota-USA hybrids, perhaps also inactivating many X-bearing as well as Y-bearing sperm, we presently have no evidence for such systems.
We also do not claim, however, that segregation distortion plays no role in Bogota-USA hybrid sterility. Instead, while our results suggest an association between hybrid segregation distortion and hybrid male sterility, they do not currently allow us to either accept or reject the hypothesis that segregation distortion causes hybrid sterility. Indeed it is worth noting that all of our findings can be accommodated by the more moderate hypothesis that hybrid segregation distortion contributes to, but is not the sole cause of, hybrid male sterility. Interestingly, TAO et al. (2001) arrived at a similar conclusion in their analysis of D. simulans-D. mauritiana hybrids. Through an impressively fine-scale genetic analysis, Tao et al. showed that the same 80-kb region that allows hybrid segregation distortion also causes partial hybrid male sterility. They further showed, however, that complete hybrid male sterility requires the action of at least one additional autosomal locus (which they mapped and named broadie). Indeed TAO et al. (2001) speculate that hybrid segregation distortion and hybrid male sterility may often involve partially (but not completely) overlapping sets of genes.
In conclusion, the most important unanswered question now confronting us is clear: Do the genes that cause hybrid segregation distortion between the Bogota and USA subspecies also contribute to hybrid male sterility? Fortunately, this question can be resolved in a straightforward way: one need only determine if, in some chromosome region of large effect on both phenotypes, the genes causing hybrid segregation distortion can be separated meiotically from those causing hybrid male sterility (e.g., TAO et al. 2001). We are now attempting to answer this question via a large introgression experiment in which the genes causing hybrid segregation distortion and hybrid male sterility in the sepia region of XR will be fine mapped using molecular markers. This analysis will obviously be facilitated by the availability of the complete D. pseudoobscura genome sequence.
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ACKNOWLEDGEMENTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSLITERATURE CITED |
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LITERATURE CITED |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSLITERATURE CITED |
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