Condition dependent sexual selection and recombination rate evolutionPatrick D. Lorch

Biological Sciences DepartmentKent State University, Kent, Ohio, USA

AbstractOne explanation for widespread sex differences in AUTOSOMAL recombination rates is that they are caused by condition dependent sexual selection (CDSS). When this is the case, sexual selection can intensify selection on traits that affect overall condition. What CDSS means at the molecular genetic level is not clear. CDSS will likely affect how resources are allocated to different traits in each sex, and the molecular mechanism for this will likely be changes in how gene expression is regulated in males versus females. Using the example of bric-à-brac (bab) and abdominal pigmentation in Drosophila, I will describe how cis-regulatory changes can lead to the kind of epistatic interactions that will select for sex differences in autosomal recombination.

Sex differences in autosomal recombination• When mapping is done so that male and female recombination rates can be

estimated separately generally we see:•One sex has a larger linkage map, indicating higher rates of recombination.•Males have dramatically lower rates of recombination.

•Example: linkage group 25 of zebrafish (Singer et al. 2002)

Trivers observed• When recombination is greater in males than females:• Male parental investment is high.• Mating is costly for males.• e.g., grasshoppers, butterflies• i.e., when sexual selection on males is weaker

Trivers hypothesis• Sexual selection acts adaptively on groups of genes in one sex to lower

recombination rate.• Preferred males are a subset of the total males available.• They have groups of alleles at loci (in cis or imprinted) that interact well

together.•Males with lower recombination pass groups of these alleles on to offspring intact.

Condition dependent sexual selection (CDSS)• Condition - resources that can be allocated to fitness enhancing traits• Lots of genes• Lots of genetic variation due to many targets for mutation

• Condition dependence - if high condition males are better able to pay for exaggerated display• Genetic covariance between condition and sexual display should develop.

• At the genetic level, this amounts to “genic capture” (Rowe and Houle 1996)• Sexual display traits “capture” genetic variance in condition• Sexual selection should affect rates of adaptation at condition loci (Lorch et al

2003)• CDSS generates conditions that might drive evolution of sex differences in

recombination rates

How can sex differences in recombination evolve• Kinds of differences in selection and epistasis between males and females that

can drive the evolution of sex differences in recombination Lenormond 2003 Results

• Ignore haploid effects.

• Diploid stage (E = epistatic effect on fitness, s = directional selection):• E(paternal) ≠ E(maternal)• s(paternal) ≠ s(maternal)• CDSS and imprinting both may be important sources of linkage disequilibrium to make these more likely• Sex dimorphism in E(cis) - E(trans)

cis Regulatory Element (CRE) Evolution• CRE evolution will likely be responsible for most sexual dimorphism

(Williams et al 2008)• Because the same DNA is expressed in males and females• Differential regulation of CREs allows modularity and evolution of

divergent gene expression (Carroll 2008)• CREs for condition dependent traits are likely spread throughout genome

• Mutations in CREs under CDSS are more likely to have strong epistatic effect in cis compared to trans in males causing dimorphism in E(cis) - E(trans)

Evolution of bab1 “dimorphic” CRE• Novel male coloration in A5, A6

• Pigments and precursors are also used in insect immunity• Only high condition males may be able to down-regulate immunity to put on an effective display (Siva-Jothy 2000)• Predicts that evolution of CREs for immunity should cause down-regulation of immunity in males

Evolutionary changes in D. melanogaster:• Reduction in spacing between binding sites• Gain of ABD-B Hox protein binding site

• These changes may be typical of changes at all CREs under CDSS• Evolutionary remodeling of CREs may be particularly important in selecting

for reduced recombination

Conclusions• CDSS generates conditions that might drive evolution of sex differences in

recombination rates• CDSS and imprinting both may be important sources of linkage

disequilibrium to make these more likely• CREs for condition dependent traits are likely spread throughout genome• Mutations in CREs under CDSS are more likely to have strong epistatic

effect in cis compared to trans leading to selection for sex differences in recombination

• CDSS suggests that evolution of CREs for immunity should cause down-regulation of immunity in males but not females

• Evolutionary remodeling of CREs may be particularly important in selecting for reduced recombination

ReferencesCarroll, S. B. 2008. Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution. Cell 134:25-36.

Lenormand. 2003. The Evolution of Sex Dimorphism in Recombination. Genetics 163:811-822.

Lorch, P. D. 2005. Sex differences in recombination and mapping adaptations. Genetica 123:39-47.

Lorch, P. D., S. Proulx, L. Rowe, and T. Day. 2003. Condition-dependent sexual selection can accelerate adaptation. Evolutionary Ecology Research 5:867-881.

Rowe, L., and D. Houle. 1996. The lek paradox and the capture of genetic variance by condition dependent traits. Proceedings of the Royal Society of London B, Biological Sciences 263:1415-421.

Singer, A., H. Perlman, Y. Yan, C. Walker, G. Corley-Smith, B. Brandhorst, and J. Postlethwait. 2002. Sex-specific recombination rates in zebrafish (Danio rerio). Genetics 160:649-657.

Siva-Jothy. 2000. A mechanistic link between parasite resistance and expression of a sexually selected trait in a damselfly. Proceedings of the Royal Society of London, Series B 267:2523-27.

Williams, T. M., J.E. Selegue, T. Werner, N. Gompel, A. Kopp, and S.B. Carroll. 2008. The regulation and evolution of a genetic switch controlling sexually dimorphic traits in Drosophila. Cell 134:610-623.

♂♀ ♂♀ ♂♀ ♂♀

Taxon F > M M > F F = M Comments

Animals

Platyhelminthes 2 1 0

Insecta 2 9 3 Orthoptera

Amphibia 4 2 0

Mammalia 7 4 1

Pisces 2 0 0

Aves 2 0 0

Plants

Monocots 20 3 4

Dicotyledonae 2 1 1

Orchidaceae 4 1 0

Totals 45 21 9

Breakdown for 75 chiasmate species by taxon.

No difference9

M > F .21 F > M

45

(Lorch 2005)

traits develop requires the identification of those genes with sex-limited expression and elucidation of the genetic and molecularmechanisms governing their regulation. We showed that dimor-phic bab expression is regulated by a discrete CRE whoseactivity is combinatorally regulated by the direct inputs of bothregion- (ABD-B) and sex-specific (DSX) transcription factors. Infemales, ABD-B acts in concert with the DSXF isoform throughbinding sites in the dimorphic element to activate bab expressionin the posterior segments. Whereas in males, ABD-B activity isoverridden by the repressive activity of the DSXM isoform whichbinds to the same sites as DSXF and hence, permits the forma-tion of the male-specific posterior pigmentation (Figure 7A).

The genetic pathways that regulate sex-determination andsexual differentiation differ greatly across the animal kingdom,so this mode of male-specific trait regulation in Drosophila maynot apply in detail to other animals. However, the integration ofregion- and sex-specific regulatory inputsmust be a requirementfor the production of dimorphic traits. We suggest that the inte-gration of such combinatorial inputs by cis-regulatory elements,

Figure 7. Model for the Operation andEvolution of the Dimorphic Genetic Switch(A) The operation of the switch. Expression of bab

in the posterior abdominal segments A5–A7 of fe-

males is mediated by the combined inputs of the

segment-specific HOX protein ABD-B and the

female-specific isoform DSXF. Expression of bab

results in the repression of full tergite pigmentation

in these segments. Expression of bab in male seg-

ments A5 and A6 is repressed by themale-specific

isoform DSXM. The absence of bab expression

in these segments allows for the development

of fully-pigmented tergites.

(B) The evolution of the switch. Schematic depic-

tion of the evolution of the dimorphic element

from the inferred common ancestor of D. mela-

nogaster and D. willistoni. Yellow boxes indicate

binding sites for ABD-B and white boxes indicate

DSX binding sites. Yellow and white ovals repre-

sent ABD-B and DSX protein monomers respec-

tively. The common ancestral CRE contained two

and thirteen orthologous binding sites for DSX

and ABD-B, respectively. In the lineage leading

to D. wil., ABD-B site 8 was lost, the polarity of

Dsx1 was reversed (red arrow) and candidate

ABD-B binding sites 12a and 12b were gained

(red stars). In the lineage leading to D. mel., inter-

binding site spacing was reduced in regions I, II,

and III, and ABD-B site 13 was gained (blue star),

which collectively contributed to the higher level

of gene expression in female segments A5 and A6.

as we have demonstrated for bab, is ageneral feature of genetic switches withinthe pathways regulating the production ofdimorphic traits.

The Evolution of a New DimorphicTraitThe origins of sexually dimorphic traitshave long been of central interest in evo-

lutionary biology. One of the key questions that Darwin (Darwin,1871) grappled with, as have many others subsequently (Fisher,1930), waswhether dimorphic traits are limited to one sex at theirorigin, or whether these traits first appear in both sexes and thenbecome restricted to one sex. This question has been particu-larly important and challenging in terms of genetics and evolu-tionary theory, as it has not been resolved previously how theeffects of mutations could be restricted to one sex.In the simplest genetic scenarios of sexual dimorphism,

male-limited traits are the products of the male-limited expres-sion of specific genes. The main evolutionary question then, asit has been phrased in classical genetic terms, is whether male-limited gene expression evolves via: (1) ‘‘alleles’’ that are ex-pressed only in males; or (2) alleles expressed in both sexeswhich are then suppressed in females or promoted in males(Coyne et al., 2008). The elucidation of the regulation andevolution of male-specific pigmentation provides a uniqueopportunity to reconstruct the genetic path of the evolution ofa dimorphic trait.

620 Cell 134, 610–623, August 22, 2008 ª2008 Elsevier Inc.

this pattern in D. melanogaster, which requires the activities ofseveral enzymes involved in pigment production as well as sev-eral transcription factors (Wittkopp et al., 2003). Two central reg-ulators of posterior pigmentation are the proteins encoded by thetandemly duplicated genes bab1 and bab2 of the bab locus.Both genes encode DNA-binding proteins (Lours et al., 2003)that act as dominant repressors of pigmentation (Coudercet al., 2002; Kopp et al., 2000). While female pupae expressbab in abdominal segments A2–A6, bab expression in males islimited to segments A2–A4, and the relative absence of babexpression in segments A5 and A6 is necessary for their greaterpigmentation in males (Kopp et al., 2000). Genetic analyses haveimplicated the Hox gene Abd-B as a repressor of bab in theseposterior segments and suggested that repression of bab is miti-gated in females by the activity of dsxF, the sex-specific tran-script derived from the doublesex (dsx) locus (Kopp et al.,2000). The male-specific repression of bab appears to haveevolved from an ancestral monomorphic condition in whichbab was expressed in the posterior of both sexes.

In order to understand the molecular mechanisms by whichbab expression is regulated and has evolved, we sought to iden-tify the CREs governing bab expression, to characterize the di-rect transcriptional regulators of their CREs, and to trace howfunctional changes in gene expression have occurred inDrosophila evolution. We found that two CREs govern bab ex-pression in the pupal abdomen. These include one elementthat regulates bab expression in segments A2–A4 of both sexesand a second, dimorphic element that regulates expression inthe posterior segments A5–A7 of females. We demonstratethat the dimorphic element is part of a genetic switch that, incombination with the HOX protein ABD-B and the sex-specificactivities of the male and female isoforms of the DSX protein, di-rects female-specific activation and male-specific repression ofbab in posterior segments. Surprisingly, we found that both thepresence of this dimorphic CRE and its regulation by ABD-Band DSX predated the origin of dimorphic pigmentation. We dis-covered that the new domain of dimorphic CRE activity requiredfor dimorphic pigmentation evolved from many fine-scale

Figure 1. Bab1 Expression in the Abdomen Is Regulated by Two CREs(A andB) Dorsal view ofD.melanogaster adult abdomens.Male segments A5 and A6 are fully pigmented (A). In females, pigmentation of these segments is limited

to a posterior stripe (B).

(C and D) Expression of Bab1 inmale and female pupae at 72 hr APF. Bab1 expression in males is limited to segments A2–A4 (C), but in females, Bab1 expression

extends into segments A5 and A6, as well in the female-specific segment A7 (D).

(E) Two CREs, the anterior element and dimorphic element, reside in the large 1st intron of bab1 and govern Bab expression in the abdominal epidermis.

(F–I) GFP-reporter expression in dorsal pupal abdomens.

(F and G) The anterior element drove GFP-reporter gene activity in segments A2-A4 of both males (F) and females (G).

(H) The dimorphic element was inactive in males.

(I) The dimorphic element drove reporter expression in female segments A5–A7, with levels increasing from the anterior to posterior.

Cell 134, 610–623, August 22, 2008 ª2008 Elsevier Inc. 611

Williams et al 2008 results: bab1 dimorphic element

Drosophila melanogaster

Mom Dad

cis trans

cis

cis

cis

cis trans cis

parental parental