Genetic dissimilarity, genetic diversity, and mate preferences in humans

Evolution and Human Behavior 31 (2010) 48 – 58

Genetic dissimilarity, genetic diversity, and mate preferences in humans Hanne. C. Liea,b,⁎, Leigh W. Simmonsb , Gillian Rhodesa b

a School of Psychology, University of Western Australia, Crawley, WA, Australia Centre for Evolutionary Biology, School of Animal Biology, University of Western Australia, Crawley, WA, Australia Initial receipt 2 April 2009; final revision received 5 July 2009

Abstract It is clear that genes at the major histocompatibility complex (MHC) are involved in mate preferences in a range of species, including humans. However, many questions remain regarding the MHC's exact influence on mate preference in humans. Some research suggests that genetic dissimilarity and individual genetic diversity (heterozygosity) at the MHC influence mate preferences, but the evidence is often inconsistent across studies. In addition, it is not known whether apparent preferences for MHC dissimilarity are specific to the MHC or reflect a more general preference for genome-wide dissimilarity, and whether MHC-related preferences are dependent on the context of mate choice (e.g., when choosing a short-term and long-term partner). Here, we investigated whether preferences for genetic dissimilarity are specific to the MHC and also whether preferences for genetic dissimilarity and diversity are context dependent. Genetic dissimilarity (number of alleles shared) influenced male, but not female, partner preferences, with males showing a preference for the faces of MHC-dissimilar females in both mating contexts. Genetic diversity [heterozygosity (H) and standardized mean (d2)] influenced both male and female preferences, regardless of mating context. Females preferred males with greater diversity at MHC loci (H) and males preferred females with greater diversity at non-MHC loci (d2) in both contexts. Importantly, these findings provide further support for a special role of the MHC in human sexual selection and suggest that male and female mate preferences may work together to potentially enhance both male and female reproductive success by increasing genetic diversity in offspring. © 2010 Elsevier Inc. All rights reserved. Keywords: MHC; Mate preferences; Genetic diversity; Genetic similarity; Disassortative mate preferences; Facial attractiveness

1. Introduction The major histocompatibility complex (MHC, or human leukocyte antigen, HLA, in humans) is found in all jawed vertebrates and contains genes that are implicated in many important biological functions, including immune functioning (Doherty & Zinkernagel, 1975; Lechler & Warrens, 2000) and mate preferences (reviewed in Havlicek & Roberts, 2009; Milinski, 2006). Because MHC genes are important for several aspects of individual fitness, they are particularly good candidates for studying the genetic benefits of mate choice (Apanius, Penn, Slev, Ruff, & Potts, 1997; Schwensow, Fietz, Dausmann, & Sommer, 2008; Tregenza & Wedell, 2000). MHC genes are directly involved in immune functioning, where each allele codes for peptides ⁎ Corresponding author. School of Psychology (M304), University of Western Australia, Crawley, WA 6009, Australia. Tel.: +61 8 6488 3573; fax: +61 8 6488 1006. E-mail address: [email protected] (H.C. Lie). 1090-5138/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.evolhumbehav.2009.07.001

that can detect a restricted range of antigens derived from pathogens and parasites. MHC alleles are expressed codominantly. Therefore, increased allelic diversity at the MHC should be beneficial as it broadens the range of antigens an individual can detect and present to T cells for destruction (Doherty & Zinkernagel, 1975). There is evidence that greater MHC diversity (heterozygosity) enhances immunocompetence in some cases (e.g., Carrington et al., 1999; Duggal et al., 2004; Froeschke & Sommer, 2005; Hraber, Kuiken, & Yusim, 2007; McClelland, Penn, & Potts, 2003; Oliver, Telfer, & Piertney, 2009; Schwensow, Fietz, Dausmann, & Sommer, 2007; Thursz, Thomas, Greenwood, & Hill, 1997), although not in all (e.g., Hill et al., 1991; Meyer-Lucht & Sommer, 2005). The exact effects of the MHC on mate preferences in humans are still debated, but are likely to involve preferences for MHC diversity (heterozygosity) and/or compatibility of parental MHC genotypes (e.g., Havlicek & Roberts, 2009; Roberts, Hale, & Petrie, 2006; Tregenza & Wedell, 2000). For example, the disassortative mating hypothesis proposes

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that individuals may prefer mates with dissimilar MHC alleles to avoid inbreeding and to gain indirect benefits in terms of increased genetic diversity and disease resistance in offspring (Brown, 1997, 1999; Freeman-Gallant, Meguerdichian, Wheelwright, & Sollecito, 2003; Penn & Potts, 1998; Potts, Manning, & Wakeland, 1991; Tregenza & Wedell, 2000; Yamazaki et al., 1976; Ziegler, Kentenich, & Uchanska-Ziegler, 2005). Additionally, the good-genes-asheterozygosity hypothesis (Brown, 1997, 1999) proposes that MHC diversity should be preferred in a mate if it is associated with individual quality. Preferences for MHCdiverse mates could therefore be adaptive because highquality mates should be able to provide direct benefits, including parental care, resources, and reduced risk of contagion to their partner and offspring (Kirkpatrick & Ryan, 1991; Roberts, Little, Gosling, Perrett, et al., 2005; Sauermann et al., 2001). Moreover, choosing a genetically diverse, or heterozygous, mate could also potentially increase genetic variability in the offspring since heterozygosity is on average heritable (Hoffman, Forcada, Trathan, & Amos, 2007; Mitton, Schuster, Cothran, & De Fries, 1993). Mate preferences for genetic diversity and dissimilarity are not mutually exclusive, and both may contribute to the maintenance of high levels of polymorphism observed at MHC loci (e.g., Apanius et al., 1997; Piertney & Oliver, 2006). Preferences for MHC-dissimilar mates have been found in a range of nonhuman species, including lizards (Olsson et al., 2003), fish (Landry, Garant, Duchesne, & Bernatchez, 2001), birds (Freeman-Gallant et al., 2003; but see Bonneaud, Chastel, Federici, Westerdahl, & Sorci, 2006), and mice (Penn & Potts, 1998; Potts et al., 1991; Yamazaki et al., 1976), while female sticklebacks choose mates to achieve an intermediate level of MHC diversity in their offspring (Aeschlimann, Haberli, Reusch, Boehm, & Milinski, 2003; Milinski, 2003, 2006). In humans, studies of preferences for MHC dissimilarity in mates yield inconsistent results (recently reviewed in Havlicek & Roberts, 2009). Couples were found to be more dissimilar at the MHC than by chance in two reproductively isolated populations, in the Hutterites (Ober et al., 1997) and Mormons (Chaix, Cao, & Donnelly, 2008), but not across the genome (Mormon sample), suggesting that the dissimilarity preference is specific to the MHC (Chaix et al., 2008). However, no evidence of MHC-based mate choice in couples was found in studies across a range of ethnic populations (Chaix et al., 2008; Hedrick & Black, 1997; Ihara, Aoki, Tokunaga, Takahashi, & Juji, 2000; Jin, Speed, & Thompson, 1995; Nordlander et al., 1983; but see Rosenberg, Cooperman, & Payne, 1983). Interestingly, increased MHC similarity in romantic couples has been associated with relationship dissatisfaction and a tendency to seek extra-pair partners for females (GarverApgar et al., 2006). In the laboratory, a female preference for the odor of MHC-dissimilar males was found in two studies (Wedekind & Furi, 1997; Wedekind, Seebeck, Bettens, & Paepke, 1995)

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but not in two larger studies (Roberts, Gosling, Carter, & Petrie, 2008; Thornhill et al., 2003). Additionally, Jacob, McClintock, Zelano, & Ober (2002) found a female preference for an intermediate level of MHC dissimilarity in males. Of three studies testing male preferences for female odor, two found a preference for MHC dissimilarity (Thornhill et al., 2003; Wedekind & Furi, 1997; see also Santos, Schinemann, Gabardo, & da Graca Bicalho, 2005). Only one study has directly tested preferences for MHC dissimilarity in faces. Roberts, Little, Gosling, Jones, et al. (2005) conducted a study where each female rater was “prematched” with three MHC-similar and three MHCdissimilar males. Contrary to past studies where a female preference for the odor of MHC-dissimilar males has been reported, Roberts, Little, Gosling, Jones, et al. (2005) found a female preference for the faces of MHC-similar men (see also Roberts, Little, Gosling, Perrett, et al., 2005). Roberts et al. suggested that the MHC-similarity preference is consistent with familial imprinting studies showing assortative preferences for facial appearance among actual couples (e.g., Bereczkei, Gyuris, Koves, & Bernath, 2002; Bereczkei, Gyuris, & Weisfeld, 2004). Thus, in humans, the current evidence for the MHC-disassortative mating hypothesis is mixed. Preferences for genetic diversity (heterozygosity) at the MHC have been found in some nonhuman animals (reviewed in Kempenaers, 2007). For example, female fattailed dwarf lemurs (Cheirogaleus medius) prefer their social and extra-pair mates to be genetically diverse at both MHC and non-MHC loci (Schwensow, Fietz, et al., 2008). MHC diversity also predicted male mating success in rhesus macaques (Macaca mulatta, Sauermann et al., 2001). In humans, laboratory studies suggest that females prefer both the odor and the faces of men who have greater genetic diversity at MHC loci compared to less diverse males (Lie, Rhodes, & Simmons, 2008; Roberts, Little, Gosling, Perrett, et al., 2005; Thornhill et al., 2003), even when controlling for diversity at non-MHC loci (Lie et al., 2008). However, males do not show a preference for MHC diversity in female faces (Coetzee et al., 2007; Lie et al., 2008; Thornhill et al., 2003), but may prefer genetic diversity at loci outside the MHC (Lie et al., 2008). Thus, at least female preferences for male MHC diversity appear to be consistent with the good genes as heterozygosity hypothesis in humans. Although there is evidence for MHC-related influences on mate preferences in many species (Havlicek & Roberts, 2009; Milinski, 2006; Penn, 2002; Penn & Potts, 1999), little is known about the relative importance of the MHC versus genetic background since most studies do not control for the potential influence of non-MHC loci (but see Chaix et al., 2008; Lie et al., 2008; Reusch, Häberli, Aeschlimann, & Milinski, 2001; Schwensow, Fietz, et al., 2008). Moreover, in humans, little is known about whether preferences for MHC dissimilarity or diversity are dependent on the mating context. That is, are they equally preferred in short-term and long-term mates? Roberts, Little, Gosling, Jones, et al.

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(2005), the only study to compare MHC effects in the two mating contexts, found that the preference for MHC similarity in faces was strongest in the long-term condition. Similarly, although they did not include a short-term context, Roberts, Gosling, Carter, & Petrie (2008) found that rating odors specifically for desirability as a long-term partner elicited stronger MHC-related effects than when rating odors for “pleasantness.” Thus, MHC-related preferences may be influenced by the mating context. Here, we explored whether genetic dissimilarity and genetic diversity, within and outside the MHC, influence partner preferences, and whether such preferences are context dependent. We investigated for the first time whether MHC dissimilarity predicts face preferences while controlling for genetic dissimilarity at loci outside the MHC. Rather than comparing attractiveness ratings of high and low MHC dissimilar individuals (as in Roberts, Little, Gosling, Jones, et al., 2005; Wedekind et al., 1995), we used genetic dissimilarity as a continuous variable (as in Jacob, McClintock, Zelano, & Ober, 2002; Wedekind & Furi, 1997), and investigated its effect on attractiveness preferences. This study is also the first to test whether males prefer the faces of MHC-dissimilar females. Although females are expected to be the choosier sex according to parental investment theory (Trivers, 1972), it should also be adaptive for males to maximize the genetic quality of offspring, especially in species, such as humans, where males have low potential to reproductively monopolize many females and tend to invest heavily in their partner and offspring (Cunningham & Birkhead, 1998; Schwensow, Eberle, & Sommer, 2008; Sefcek, Brumsbach, Vasquez, & Miller, 2006). We therefore examine both female and male preferences for genetic dissimilarity in potential partners. Second, although previous research has linked MHC diversity to male facial attractiveness, and found a nonsignificant trend for general genetic diversity to predict female attractiveness (Lie et al., 2008; Roberts, Little, Gosling, Perrett, et al., 2005), we do not know whether these preferences are influenced by the mate-choice context. Human mate preferences are expected to be context dependent (e.g., Buss & Schmitt, 1993). Past research suggests that females show greater preference for facial masculinity and symmetry, which are used as putative facial signals of genetic quality, in short-term partners compared to long-term partners (Little, Jones, Penton-Voak, Burt, & Perrett, 2002). Thus, we also examine whether preferences for genetic dissimilarity and for genetic diversity are context dependent. 2. Methods 2.1. Participants The participants were 79 (32 female), heterosexual, Caucasian students at the University of Western Australia (aged between 18 and 32). They received course credit in

return for their participation, and they had all been previously genotyped and photographed (Lie et al., 2008). 2.2. Face photographs Photographs and genotype details of the faces of 79 males and 80 females were available from our database, which included the current participants. Details of the photographs are provided in Lie et al. (2008). In brief, the photographs were taken under standardized conditions, with the participants displaying a neutral expression, and with any makeup or facial hair removed. To minimize any effects of clothing and hairstyle, the color photographs were digitally fitted with an oval mask, leaving only the face and minimal hair visible (see also Roberts, Little, Gosling, Perrett, et al., 2005). 2.3. Genotyping and genetic analysis Each individual was typed at 12 MHC and at 11 nonMHC microsatellite loci (for details, see Lie et al., 2008). The 12 MHC loci are known to be in linkage disequilibrium with functional MHC genes, including the classical HLA loci A, B, C, DRB1 and DQB1 (Malkki, Single, Carrington, Thomson, & Petersdorf, 2005). Genetic dissimilarity was measured as the number of shared alleles between two individuals. For each rater and face (person in the photograph) pair, number of alleles shared was calculated using SHAREDST, available from www2.biology.ualberta. ca/jbrzusto/sharedst.php (Brzustowski, n.d.). This program uses an algorithm to estimate allelic distance between all individuals in a sample and can be used to count how many alleles each individual shares with all other individuals in the sample. Following past research (Roberts, Little, Gosling, Jones, et al., 2005; Thornhill et al., 2003; Wedekind & Furi, 1997; Wedekind et al., 1995), allele sharing was calculated as the total number of alleles shared between two individuals at MHC or at non-MHC loci. If two individuals were homozygous for the same allele at a locus, they were then counted as sharing two alleles. Observed ranges of allele sharing between all possible male–female pairs were 0–13 for non-MHC loci (mean=5.36, S.D.=0.81; possible range, 0–22) and 0–21 for MHC loci (mean=6.67, S.D.=0.91; possible range, 0-24). Following Lie et al. (2008), genetic diversity was measured separately for the MHC and non-MHC loci using heterozygosity (referred to as H), the proportion of heterozygous loci among all loci measured, and standardized mean d2, the squared difference in number of repeat units between the two alleles at a given locus, standardized by the maximum observed value at that locus, and averaged across all measured loci (Amos et al., 2001). Heterozygosity reflects whether the two alleles at a locus are the same or not, while standardized mean d2 (referred to as d2) reflects the genetic distance between two alleles at a locus, averaged across measured loci (Coulson et al., 1998). It should be mentioned that the observed effects of MHC genotype on appearance could potentially be driven by

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substructure within the sample, reflecting regional differences in MHC genotypes and facial characteristics, rather than actual effects of MHC diversity or similarity. Although such a confounding effect cannot be completely ruled out, it is unlikely because no evidence of substructure was found in this sample (see Lie et al., 2008).

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3.75% per rater). Interrater agreement was high across all ratings, with mean Cronbach's α=.93 (range, .89–.95), indicating that there was high interrater consistency in the attractiveness rankings of the faces.

3. Results 2.4. Attractiveness ratings Participants rated photographs of opposite-sex individuals for attractiveness in two mate-choice contexts, as a short-term partner and as a long-term partner. The two ratings were completed at two different rating sessions, conducted over the internet, with a minimum of 2 weeks between rating sessions. Of the 32 female raters, 22 females rated the males in both contexts (six rated short-term attractiveness only and four rated long-term attractiveness only). Of the 47 male raters, 38 males rated the females in both contexts (four rated short-term attractiveness only and five rated long-term attractiveness only). The photographs were presented in one of two random orders for both shortterm and long-term attractiveness ratings. The participants were assigned randomly to order of presentation and viewed all the faces in the sample before rating them for attractiveness as a short- or long-term partner on a scale from 1 (not attractive at all) to 10 (extremely attractive). Description of short term and long term was based on Stewart, Stinnett, and Rosenfeld (2000). A short-term relationship was defined as a single date accepted on the spur of the moment, an affair within a long-term relationship, and the possibility of a one-night stand. A long-term relationship was defined as a relationship with someone you may want to move in with, someone you may consider leaving your current partner to be with, and someone you may, at some point, wish to marry (or enter into a relationship on similar grounds as marriage). We standardized the attractiveness ratings from each rater to control for individual differences in scale use (Roberts, Little, Gosling, Jones, et al., 2005; Roberts, Little, Gosling, Perrett, et al., 2005). Ratings of each individual face were averaged across the raters, while excluding faces familiar to the rater (on average

3.1. The relationship between short-term and long-term partner attractiveness ratings We first investigated the degree of consistency between attractiveness ratings across the two contexts (short-term and long-term partners). Table 1 shows the descriptive statistics and Spearman ρ correlation coefficients for the genetic diversity and attractiveness variables for male faces (n=79) and female faces (n=80). The mean attractiveness ratings in the short-term and long-term partner context correlated highly for both males and females (both rS's N.92, Table 1), suggesting a strong relationship between which faces people prefer across contexts. However, these high correlations may misrepresent such a relationship because they do not reflect differences at the level of the individual but rather at a group level. To investigate differences in preference within the individual, we correlated each rater's attractiveness ratings of the same faces in the short-term and in the long-term context. We used Spearman's ρ correlation coefficients (rS) as some of the individual attractiveness rating distributions were skewed. The mean correlation coefficients between short-term and long-term attractiveness across individuals were substantial but considerably lower than for the group-level coefficients for male raters (mean rS=0.54; S.D.=0.16; range, 0.13–0.78; n=37) and among female raters (mean rS=0.58; S.D.=0.14; range, 0.26–0.81; n=22). Thus, there was potential for genetic dissimilarity and diversity to influence preferences for short-term and long-term partners in different ways. 3.2. Genetic dissimilarity and facial attractiveness Next, we examined whether attractiveness ratings were influenced by genetic dissimilarity, measured as the number

Table 1 Means, standard deviations (S.D.), ranges, and Spearman’s ρ correlation coefficients for the genetic diversity and attractiveness variables presented separately for males (below the diagonal, n=79) and females (above the diagonal, n=80) Non-MHC-H

Non-MHC-H MHC-H Non-MHC-d2 MHC-d2 Short-term Long-term ⁎ pb.05. ⁎⁎ pb.01. ⁎⁎⁎ pb.001.

MHC-H

0.12 0.17 0.31⁎⁎ 0.13 −0.04 −0.02

−0.12 0.23⁎ 0.21 0.29⁎⁎

Non-MHC-d2 0.33⁎⁎ 0.00 0.00 −0.14 −0.16

MHC-d2

0.09 0.55⁎⁎⁎ 0.10 0.04 0.11

Mating context

Males

Short-term

Long-term

Mean±S.D.

Range

Mean±S.D.

Range

0.08 0.07 0.30⁎⁎ −0.05

0.11 0.02 0.27⁎ −0.11 0.95⁎⁎⁎

0.83±0.12 0.84±0.14 0.15±0.06 0.17±0.07 3.53±0.94 3.52±1.05

0.55–1.00 0.42–1.00 0.04–0.34 0.07–0.35 1.91–6.25 1.65–6.46

0.84±0.13 0.83±0.13 0.16±0.07 0.17±0.07 3.93±0.91 4.13±0.93

0.37–1.00 0.30–1.00 0.05–0.40 0.05–0.36 1.98–6.56 2.30–6.70

0.93⁎⁎⁎

Females

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Table 2 The mean regression slopes (β) of the number of non-MHC and MHC alleles shared with male raters predicting female facial attractiveness and their 95% confidence intervals averaged across 80 hierarchical multiple regression models Contexta Short-term Non-MHC MHC Long-term Non-MHC MHC

Mean β (95% CI)

t(80)

p

Range of β's

Negative/total β's

−0.03 (−0.07 to 0.01) −0.10 (−0.13 to −0.06)

−1.69 −5.72

.096 b.0001

−0.35 to 0.34 −0.48 to 0.29

48/80 59/80⁎

−0.01 (−0.05 to 0.02) −0.11 (−0.14 to −0.07)

−0.75 −5.54

.454 b.0001

−0.43 to 0.31 −0.48 to 0.29

47/80 59/80⁎

Number of non-MHC and MHC alleles shared was entered in Block 1 and Block 2, respectively. The t and p values are from single-sample t tests comparing the mean β to zero. The range of β's and the number of negative β of total number of β are also provided. a Context refers to whether the faces were rated for attractiveness as short-term or as long-term partners. ⁎ Sign test pb.001, comparing the number of observed negative β's to chance (40/80).

of alleles shared between the rater and the person being rated. We used analyses that treat the face (the individual being rated) as the unit of analysis. This approach has the greatest power to detect preferences for MHC dissimilarity because it controls for factors other than allele sharing that may influence a person's attractiveness (Roberts, Little, Gosling, Jones, et al., 2005; Thornhill et al., 2003; Wedekind et al., 1995). Because we were interested in the effect of MHC dissimilarity on attractiveness ratings (both short-term and long-term) after controlling for effects of non-MHC dissimilarity, we used hierarchical multiple regression models where non-MHC dissimilarity was entered in the first block and MHC dissimilarity in the second block. This procedure allowed us to assess whether MHC dissimilarity affects attractiveness ratings over and above non-MHC similarity. Thus, for each face being rated (80 female faces and 79 male faces), we used the number of non-MHC and MHC alleles shared with the rater to predict the attractiveness ratings in both the short-term and long-term contexts. Normality of residuals was checked for each model. For female faces, this resulted in 80 β's for each predictor variable (i.e., non-MHC and MHC dissimilarity) in each context, and for male faces, in 79 β's for each predictor in each context. We then calculated the average regression slope, “mean β,” for each predictor in each context, separately for the female and the male faces. To test for non-MHC or MHC-dissimilar preferences, we compared their respective mean β's to

zero using single-sample t tests (all reported p values are two-tailed). 3.2.1. Genetic dissimilarity and female facial attractiveness There was a significant effect of MHC dissimilarity on female attractiveness. After controlling for non-MHC dissimilarity, males preferred the faces of MHC-dissimilar females. That is, females who shared fewer MHC alleles with the males received higher attractiveness ratings than females who shared more MHC alleles, in both the shortterm and the long-term attractiveness context (Table 2). There was one β value for MHC allele sharing that was more than three standard deviations below the mean in the short-term context. Removing this outlier did not influence the effect of MHC dissimilarity on attractiveness ratings [mean β (95% CI)=−0.09 (−0.12 to −0.06), t(78)= −5.72, pb.0001]. There was also a nonsignificant trend for female faces that shared fewer non-MHC alleles with the males to be rated as more attractive in the short-term attractiveness context (Table 2). This trend became significant when removing one β value for non-MHC allele sharing that was more than three standard deviations above the mean in the short-term context [mean β (95% CI)=−0.04 (−0.07 to −0.01), t(78)=2.26, p=.026]. Thus, genetic dissimilarity at the MHC, and possibly outside the MHC, appears to influence males' preferences for female facial attractiveness.

Table 3 The mean regression slopes (β) of number of non-MHC and MHC alleles shared with female raters predicting male facial attractiveness and their 95% confidence intervals averaged across 79 hierarchical multiple regression models Contexta Short-term Non-MHC MHC Long-term Non-MHC MHC

Mean β (95% CI)

t(79)

p

Range of β's

Negative/total β's

0.04 (−0.09 to 0.01) 0.00 (−0.05 to 0.05)

−1.75 0.00

.085 1.00

−0.57 to 0.40 −0.41 to 0.46

46/79 40/79

−0.02 (−0.05 to 0.01) −0.01 (−0.06 to 0.04)

−1.16 −0.23

.252 .818

−0.34 to 0.32 −0.50 to 0.59

45/79 37/79

Number of non-MHC and MHC alleles shared was entered in Block 1 and Block 2, respectively. The t and p values are from single-sample t tests comparing the mean β to zero. The range of β's and the number of negative β of total number of β are also provided. a Context refers to whether the faces were rated for attractiveness as short-term or as long-term partners.

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Table 4 Hierarchical multiple regression models of female attractiveness as short-term or long-term partner regressed on non-MHC- and MHC-heterozygosity, or on nonMHC- and MHC-standardized mean d2 Contexta Short-term Long-term

Short-term Long-term

B±95%CI Heterozygosity Non-MHC-H MHC-H Non-MHC-H MHC-H Standard mean d2 Non-MHC-d2 MHC-d2 Non-MHC-d2 MHC-d2

β

S.E.

t

p

R2/ΔR2

0.85 (−0.80 to 2.51) 0.59 (−1.03 to 2.22) 1.17 (−0.45 to 2.78) 0.12 (−1.46 to 1.71)

0.83 0.82 0.81 0.80

0.119 0.085 0.167 0.018

1.03 0.73 1.44 0.15

.309 .470 .154 .878

0.03/0.01

3.67 (0.56 to 6.78) −0.55 (−3.48 to 2.36) 3.37 (0.33 to 6.41) −1.03 (−3.88 to 1.83)

1.56 1.47 1.53 1.44

0.261 −0.042 0.245 −0.080

2.35 −0.38 2.21 −0.72

.021 .706 .030 .476

0.07*/0.00

0.03/0.00

0.06*/0.01

Only Block 2 results are presented, n=80 (full models are available online as Supplementary Data Appendix A, Table S1). a Context refers to whether the faces were rated for attractiveness as short-term or as long-term partners.

3.3.1. Genetic diversity and female facial attractiveness When measuring genetic diversity as heterozygosity, neither non-MHC-H nor MHC-H predicted female attractiveness in either context (Table 4). However, when measuring genetic diversity as genetic distance (d2), female facial attractiveness was significantly predicted by nonMHC diversity (non-MHC-d2) in both the short-term and the long-term context. More genetically diverse females were rated as more attractive than less diverse females. NonMHC-d2 explained 7% of the variance in short-term attractiveness ratings and 6% of variance in long-term attractiveness ratings. MHC-d2 did not, however, predict female facial attractiveness in either context. Thus, males appear to prefer non-MHC, but not MHC, diversity in a partner regardless of the mate-choice context.

3.2.2. Genetic dissimilarity and male facial attractiveness We found no evidence for an effect of genetic dissimilarity, at either non-MHC or MHC loci, on attractiveness ratings of male faces made by female raters in either context (Table 3). 3.3. Genetic diversity and facial attractiveness We also investigated whether genetic diversity predicted attractiveness in both rating contexts. Again, we used hierarchical multiple regression models and regressed either short-term or long-term attractiveness on non-MHC diversity (H or d2, entered in Block 1), and MHC diversity (H or d2, entered in Block 2) to assess whether MHC diversity affects attractiveness ratings over and above non-MHC diversity. Analyses were conducted separately for males and females. Attractiveness ratings in both the short-term and long-term contexts were normally distributed, but all of the genetic diversity distributions were negatively skewed. The skewed distributions were left untransformed, because the residuals of each model were normally distributed (and using transformed variables did not change the results reported, data not shown).

3.3.2. Genetic diversity and male facial attractiveness When measuring genetic diversity as heterozygosity, male facial attractiveness was significantly predicted by MHC diversity (MHC-H), after controlling for non-MHCH, in both the short-term and the long-term context (Table 5). That is, females preferred the faces of males with greater MHC diversity compared to less diverse males.

Table 5 Hierarchical multiple regression models of male attractiveness as short-term or long-term partner regressed on non-MHC- and MHC-heterozygosity, or on nonMHC- and MHC-standardized mean d2 Contexta Short Long

Short Long

Heterozygosity Non-MHC-H MHC-H Non-MHC-H MHC-H Standard mean d2 Non-MHC-d2 MHC-d2 Non-MHC-d2 MHC-d2

B±95%CI

S.E.

β

t

p

R2/ΔR2

−1.04 (−2.99 to 0.91) 1.72 (0.08 to 3.38) −0.82 (−2.54 to 0.90) 2.07 (0.61 to 3.52)

0.98 0.83 0.86 0.73

−0.121 0.237 −0.106 0.315

−1.07 2.08 −0.95 2.83

.289 .041 .346 .006

0.06*/0.05*

−1.83 (−5.53 to 1.87) −0.02 (−3.52 to 3.48) −2.27 (−5.57 to 1.03) 0.89 (−2.23 to 4.02)

1.86 1.76 1.66 1.57

−0.112 −0.001 −0.155 0.064

−0.99 −0.01 −1.37 0.57

.328 .992 .175 .571

0.01/0.00

Only Block 2 results are presented, n=79 (full models are available online as Supplementary Data Appendix A, Table S2). a Context refers to whether the faces were rated for attractiveness as short-term or as long-term partners.

0.10**/0.10**

0.03/0.00

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MHC-H explained 5% of the variance in short-term attractiveness ratings and 10% of the variance in the long-term attractiveness ratings. Non-MHC-H did not predict attractiveness of male faces in either context. MHC-H explained significantly more variance than nonMHC-H in both short-term [F change(1,76)=4.34, p=.041] and long-term attractiveness [F change(1,76)=7.99, p=.006]. Neither non-MHC-d2 nor MHC-d2 predicted male facial attractiveness in either context (Table 5). Thus, females show a preference for MHC diversity (H) in both short-term and long-term partners. 4. Discussion We investigated whether genetic dissimilarity and genetic diversity at both MHC and non-MHC loci influence human mate preferences in short-term and long-term contexts. We found for the first time that males show a specific preference for MHC-dissimilar females, after controlling for non-MHCdissimilarity, in both short-term and long-term partners. Moreover, there may also be a weak effect of non-MHC dissimilarity on male preferences for female faces, at least in short-term partners. A second novel finding was that preferences for genetic diversity in a mate do not appear to be context dependent. Extending the finding of Lie et al. (2008), we found that nonMHC diversity (d2) predicted female facial attractiveness in both partner contexts, whereas MHC diversity (H) predicted attractiveness in male faces in both contexts. Importantly, our results provide some evidence for both the disassortative mating hypothesis and the “good-genes as heterozygosity hypothesis,” and are discussed below. 4.1. Genetic dissimilarity and facial attractiveness Our findings that males prefer the faces of females that are MHC-dissimilar, and possibly non-MHC-dissimilar, imply that faces contain cues to genetic dissimilarity, both at the MHC and in general. They also add to the evidence that the MHC may play a special role in human sexual selection because MHC dissimilarity influenced face preferences when controlling for non-MHC-dissimilarity. Contrary to Roberts, Little, Gosling, Jones, et al. (2005) (see also Roberts, Little, Gosling, Perrett, et al., 2005), we found no evidence for an influence of genetic similarity on female preferences for male faces at either MHC or non-MHC loci. The discrepancy in the previous findings and the current findings could potentially reflect differences in the designs of the two studies. First, Roberts et al. measured MHC similarity across three MHC genes (HLA-A, HLA-B, and HLA-DRB1), whereas we used 12 microsatellite markers in linkage with at least one MHC gene (including HLA-A, HLA-B, and HLA-DRB1; Malkki et al., 2005), and that span a larger area of the MHC region than the three MHC genes. Second, importantly, we controlled for genetic similarity at non-MHC loci, which Robert et al. did not. Third, rather than

prematching raters with a few faces (n=6) in terms of MHC similarity and dissimilarity, our subjects rated a large sample of opposite-sex faces (n=79 or 80), thus allowing us to examine continuous variation in the effect of genetic similarity on face preferences. However, our sample of raters was smaller than the sample of Roberts et al. (n=32 vs. 92), which might make a weak MHC-similarity preference harder to detect. Lastly, Roberts et al. used female raters who were not taking oral contraception and at their most fertile period in their menstrual cycle, whereas we did not control for contraceptive use. However, if contraceptive use increases females' preferences for MHC similarity as suggested by the odor preference study of Roberts et al. (2008), then this should increase, not hamper, our chances of finding assortative preferences. Arguably, Roberts' method may be more sensitive than our method to detect any MHC similarity preferences by comparing extreme groups. However, we found significant dissimilarity preferences for males, suggesting that the lack of effect in females was not due to insufficient sensitivity. Thus, our results do not lend support to the conclusion of Roberts et al. (2005) that face preferences in humans are MHC-assortative. Rather, we found evidence for MHC disassortative preferences across two mating contexts. Altogether, the differences in experimental designs render a direct comparison of results impossible. Further research is needed to determine whether face preferences are assortative or disassortative, and whether the apparent sex difference in preferences is robust. The lack of an effect of MHC similarity on female preferences is in line with two recent odor preference studies that did not find any preference for the odor of MHC similar males (Roberts et al., 2008; Thornhill et al., 2003). Additionally, the male MHC dissimilarity preference for female faces is consistent with the findings that males prefer the scent of MHC-dissimilar females (Thornhill et al., 2003; Wedekind & Furi, 1997). It is also consistent with two studies that found actual couples to be more MHC dissimilar than expected by chance (Chaix et al., 2008; Ober et al., 1997). The male preference for MHC-dissimilar females appears at odds with reports that couples look more similar than expected by chance (e.g., Hinsz, 1989; Little, Burt, & Perrett, 2006) and with familial imprinting studies reporting assortative facial preferences among couples (Bereczkei et al 2002; 2004). However, the perceived similarity between couples may reflect similarity in facial characteristics that are not associated with genetic similarity but rather with environmental similarity. Why would males seek genetically dissimilar females? Because human males' reproductive success is constrained by partner fertility, regardless of their own mating strategy (Buss & Schmitt, 1993), they should value fertility in their partners. A preference for MHC dissimilarity may serve to reduce fertility problems associated with increased MHC allele sharing, including longer birth intervals, recurrent spontaneous abortion, and fetal loss in humans (Beydon &

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Saftlas, 2005; Ober, 1999; Ober, Elias, Kostyu, & Hauck, 1992; Ober, Hyslop, Elias, Weitkamp, & Hauck, 1998, see also Knapp, Ha, & Sackett, 1996). One could speculate that MHC dissimilarity influenced male, but not female, mate preferences because males may be more sensitive than females to facial cues to MHC dissimilarity. Visual cues appear to be more important for male than female mate choice, whereas odor cues are more important for female mate choice (Havlicek et al., 2008; Herz & Inzlicht, 2002). Interestingly, males also use facial resemblance to assess paternity, and the allocation of parental investment to offspring (Platek et al., 2004), again suggesting that facial cues are important for male reproductive decisions. 4.2. Genetic diversity and facial attractiveness Although the relative attractiveness of potential mates varied across rating context (average rS=0.5 within individuals), preferences for genetic diversity did not appear to be context dependent. Genetic diversity was preferred in both short-term and long-term partners. Using the same male faces as in Lie et al. (2008), these results extend previous findings that MHC diversity is attractive in male faces when no mating context is specified (Lie et al., 2008; Roberts, Little, Gosling, Perrett, et al., 2005). Here, MHC diversity explained 10% of the variance in long-term attractiveness and 5% in short-term attractiveness. This difference is difficult to compare formally, but the 95% confidence intervals around the β weights of MHC-H when predicting short-term versus long-term attractiveness overlap, thus suggesting that the difference in effect sizes may not be biologically relevant. Females should prefer MHC diversity in both short-term and long-term mates because heterozygosity is somewhat heritable (Hoffman et al., 2007; Mitton et al., 1993). Moreover, provided MHC diversity is associated with fitness, choosing an MHC-diverse mate may provide both resources and reduced risk of contagion in short-term and long-term relationships as well as highquality parental care in long-term relationships (Gangestad & Scheyd, 2005; Roberts & Little, 2007). The finding that non-MHC-d2 significantly predicted female attractiveness extends the findings of Lie et al. (2008) who found a nonsignificant trend for non-MHC-d2 to predict attractiveness using the same female faces. Here, using a different sample of raters, we found that non-MHC-d2 explained 7% and 6% of the variance in attractiveness ratings in the short-term and the long-term context, respectively. Consistent with previous findings (Coetzee et al., 2007; Lie et al., 2008; Thornhill et al., 2003), there was no evidence of a male preference for MHC diversity in female faces. This lack of an MHC preference is consistent with the male preference for MHC dissimilarity in the same female faces because the most MHC-diverse female may not be the most MHC-dissimilar female to a male (see Roberts, Hale, & Petrie, 2006, for further discussion). Combined, male

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preferences for general genetic diversity and MHC dissimilarity could be adaptive as they would increase genetic diversity in offspring, and reduce potential fertility-related problems that are associated with reduced genetic diversity in females (Ober, Hyslop, & Hauck, 1999) and with increased MHC allele sharing in couples (Beydon & Saftlas, 2005; Ober, 1999). It is not clear why standardized mean d2, and not heterozygosity, should be associated with male preferences for females (discussed in Lie et al., 2008). Mean d2 has been criticized for being less sensitive to genetic diversity–fitness correlations than heterozygosity (e.g., Slate et al., 2004; Tsitrone, Rousset, & David, 2001). However, mean d2 may better detect diversity–fitness associations in large, outbred populations where most individuals are heterozygous at most loci, as is the case for our human sample (Höglund et al., 2002; Kretzmann, Mentzer, DiGiovanni, Leslie, & Amato, 2006). It is therefore possible that non-MHC-d2 provides information regarding genetic variation outside the MHC not captured by heterozygosity, including more detailed information about the inbred–outbred continuum, which may influence female fitness. Alternatively, non-MHC-H and non-MHC-d2 differ in their underlying distributions, especially when using a limited number of markers as here, which could explain some of the observed differences between associations to facial appearance. As for most other human sexual selection research, an obvious limitation of our study is that we examined mate preferences, not actual mate choice, in a laboratory setting. Although this approach has the advantage of examining mate preferences without the constraints of mate choice in the real world (Roberts & Little, 2007), the challenge for future research is to test whether these subtle preferences translate into actual behavior. Moreover, here, partner preferences were judged from color photographs. Although this allowed us to establish that humans are sensitive to phenotypic cues of genetic dissimilarity and diversity in faces, it may underestimate the cues available from real-life faces. It would be of interest to determine what other features may also signal MHC dissimilarity and MHC diversity, and the relative importance of these cues for mate choice. Future research could use more complex, naturalistic stimuli that contain richer information about an individual, for example, dynamic video clips including faces, bodies, and voices, or real-life interpersonal interactions such as in a speed-datelike setting or in actual couples. In conclusion, our results add to the mounting evidence that the MHC plays a special role in human mate preferences. We found that MHC dissimilarity was especially important for male mate preference and that MHC diversity was especially important for female mate preferences. In addition, males also showed a preference for faces of females that are genetically diverse at non-MHC loci, suggesting that general genetic diversity may also play a role in human sexual selection. Moreover, both the male and female preferences appeared to be robust to the mating

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context in which partner preference judgments were made (e.g., short-term or long-term partner context). These results suggest that preferences vary between the sexes and that, combined, these preferences could work to enhance both male and female reproductive success by enhancing the genetic diversity of offspring. The next challenge lies in testing these predictions in actual couples. Acknowledgments We thank Jason Kennington, Paco Garcia-Gonzalez, Maxine Beveridge, and Davina French for advice. This work was supported by the University of Western Australia, the Australian Federation of University Women, Western Australia (AFUW-WA), and the Australian Research Council. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.evolhumbehav. 2009.07.001. References Aeschlimann, P. B., Haberli, M. A., Reusch, T. B. H., Boehm, T., & Milinski, M. (2003). Female sticklebacks Gasterosteus aculeatus use self-referencing to optimize MHC allele number during mate selection. Journal of Evolutionary Biology, 19, 558−569. Amos, W., Worthington Wilmer, J., Fullard, K., Burg, T. M., Croxall, J. P., & Bloch, D., et al. (2001). The influence of parental relatedness on reproductive success. Proceedings of the Royal Society of London B Biological Sciences, 268(1480), 2021−2027. Apanius, V., Penn, D., Slev, P. R., Ruff, L. R., & Potts, W. K. (1997). The nature of selection on the major histocompatibility complex. Critical Reviews in Immunology, 17(2), 179−224. Bereczkei, T., Gyuris, P., Koves, P., & Bernath, L. (2002). Homogamy, genetic similarity, and imprinting; parental influence on mate choice preferences. Personality and Individual Differences, 33, 677−690. Bereczkei, T., Gyuris, P., & Weisfeld, G. (2004). Sexual imprinting in human mate choice. Proceedings of the Royal Society of London - Series B: Biological Sciences, 271, 1129−1134. Beydon, H., & Saftlas, A. F. (2005). Association of human leucocyte antigen sharing with recurrent spontaneous abortions. Tissue Antigens, 65, 123−135. Bonneaud, C., Chastel, O., Federici, P., Westerdahl, H., & Sorci, G. (2006). Complex MHC-based mate choice in a wild passerine. Proceedings of the Royal Society of London B Biological Sciences, 273(1590), 1111−1116. Brown, J. L. (1997). A theory of mate choice based on heterozygosity. Behavioral Ecology, 8(1), 60−65. Brown, J. L. (1999). The new heterozygosity theory of mate choice and the MHC. Genetica, 104(3), 215−221. Brzustowski, J. Retrieved 25/11/2008 from http://www2.biology.ualberta. ca/jbrzusto/sharedst.php. Buss, D. M., & Schmitt, D. P. (1993). Sexual strategies theory: An evolutionary perspective on human mating. Psychological Review, 100, 204−232. Carrington, M., Nelson, G. W., Martin, M. P., Kissner, T., Vlahov, D., & Goedert, J. J., et al. (1999). HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science, 283(5408), 1748−1752.

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