The Desirable Dad Hypothesis: Male Same-Sex Attraction as the Product of Selection for Paternal Care via Antagonistic Pleiotropy.

Same-sex attraction, a heritable trait with a reproductive cost, lacks a comprehensive evolutionary explanation. Here we build on a hypothesis invoking antagonistic pleiotropy, which suggests that genes linked to male same-sex attraction remain in the gene pool because they have conferred some fitness advantage to heterosexual men possessing them. We posit the "desirable dad hypothesis," which proposes that alleles linked to male non-heterosexual orientations increase traits conducive to childcare; heterosexual men possessing same-sex attracted alleles are more desirable mating partners as a function of possessing superior paternal qualities. We conducted three studies to test predictions from this hypothesis. Results were consistent with all three predictions. Study 1 (N = 1632) showed that heterosexual men with same-sex attracted relatives were more feminine than men without, as indicated by self-report measures of femininity (η2 = .007), warmth (η2 = .002), and nurturance (η2 = .004 - .006). In Study 2 (N = 152), women rated feminine male profiles as more romantically appealing than masculine ones (d = 0.83)-but less so than profiles possessing a combination of feminine and masculine traits. In Study 3 (N = 153), women perceived feminine male profiles as depicting the best fathers and masculine profiles the worst (d = 1.56): consistent with the idea that femininity is attractive for childcare reasons. Together, these findings are consistent with the idea that sexual selection for male parental care may be involved in the evolution of male same-sex attraction.

Fertility of Czech Gay and Straight Men, Women, and Their Relatives: Testing the Sexually Antagonistic Gene Hypothesis.

One proposal for the persistence of homosexuality in the human population is the sexually antagonistic gene hypothesis, which suggests that the lower fertility of homosexual individuals, especially men, may be compensated by higher fertility of their relatives of the opposite sex. To test this hypothesis, we have collected data from 7,312 heterosexual men, 459 gay men, 3,352 heterosexual women, and 79 lesbian women mainly from Czechia. In an online survey, participants answered questions regarding their own as well as their parents' and grandparents' fertility. For men, we obtained no significant results except for higher fertility of gay men's paternal grandmothers, but the magnitude of this effect was very small. For the female sample, we recorded lower fertility of lesbian women's mothers and fathers. In line with our expectations, both gay men and lesbian women had lower fertility rates than their heterosexual counterparts. Our results are consistent with recent studies which likewise do not support the sexually antagonistic gene hypothesis.

Genome-Wide Linkage and Association Study of Childhood Gender Nonconformity in Males.

Male sexual orientation is influenced by environmental and complex genetic factors. Childhood gender nonconformity (CGN) is one of the strongest correlates of homosexuality with substantial familiality. We studied brothers in families with two or more homosexual brothers (409 concordant sibling pairs in 384 families, as well as their heterosexual brothers), who self-recalled their CGN. To map loci for CGN, we conducted a genome-wide linkage scan (GWLS) using SNP genotypes. The strongest linkage peaks, each with significant or suggestive two-point LOD scores and multipoint LOD score support, were on chromosomes 5q31 (maximum two-point LOD = 4.45), 6q12 (maximum two-point LOD = 3.64), 7q33 (maximum two-point LOD = 3.09), and 8q24 (maximum two-point LOD = 3.67), with the latter not overlapping with previously reported strongest linkage region for male sexual orientation on pericentromeric chromosome 8. Family-based association analyses were used to identify associated variants in the linkage regions, with a cluster of SNPs (minimum association p = 1.3 × 10-8) found at the 5q31 linkage peak. Genome-wide, clusters of multiple SNPs in the 10-6 to 10-8 p-value range were found at chromosomes 5p13, 5q31, 7q32, 8p22, and 10q23, highlighting glutamate-related genes. This is the first reported GWLS and genome-wide association study on CGN. Further increasing genetic knowledge about CGN and its relationships to male sexual orientation should help advance our understanding of the biology of these associated traits.

Human Immunodeficiency Virus Type 1 Phylodynamics to Detect and Characterize Active Transmission Clusters in North Carolina.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) phylodynamics can be used to monitor epidemic trends and help target prevention through identification and characterization of transmission clusters. METHODS: We analyzed HIV-1 pol sequences sampled in North Carolina from 1997 to 2014. Putative clusters were identified using maximum-likelihood trees and dated using Bayesian Markov Chain Monte Carlo inference. Active clusters were defined as clusters including internal nodes from 2009 to 2014. Effective reproductive numbers (Re) were estimated using birth-death models for large clusters that expanded ≥2-fold from 2009 to 2014. RESULTS: Of 14 921 persons, 7508 (50%) sequences were identified in 2264 clusters. Only 288 (13%) clusters were active from 2009 to 2014; 37 were large (10-36 members). Compared to smaller clusters, large clusters were increasingly populated by men and younger persons; however, nearly 60% included ≥1 women. Clusters with ≥3 members demonstrated assortative mixing by sex, age, and sample region. Of 15 large clusters with ≥2-fold expansion, nearly all had Re approximately 1 by 2014. CONCLUSIONS: Phylodynamics revealed transmission cluster expansion in this densely sampled region and allowed estimates of Re to monitor active clusters, showing the propensity for steady, onward propagation. Associations with clustering and cluster characteristics vary by cluster size. Harnessing sequence-derived epidemiologic parameters within routine surveillance could allow refined monitoring of local subepidemics.

Experienced homophobia and gene expression alterations in Black and Latino men who have sex with men in Los Angeles County.

Men who have sex with men (MSM) experience high rates of homophobic victimization, which is linked to myriad chronic physical and mental health disparities. Social adversity such as rejection, isolation, and racial discrimination can induce a conserved transcriptional response to adversity (CTRA) involving upregulation of proinflammatory genes and downregulation of type I interferon and antibody synthesis genes. This study specifically examines whether homophobic victimization is associated with expression of CTRA profiles in Black and Latino MSM living in Los Angeles. Analyses linked behavioral survey data with quantified RNA from leukocytes from blood samples of 70 participants over 12 months. CTRA gene expression was increased by 3.1-fold in MSM who experienced homophobic victimization while adjusting for major leukocyte subsets and sociodemographics. Accounting for all these factors, CTRA gene expression was significantly enhanced in MSM who identified as Black compared to Latino. Our findings identify experiences of homophobic victimization as drivers of inflammatory and type I interferon gene expression profiles, which can contribute to physical and mental health challenges in Black and Latino MSM.

On the Mathematics of the Fraternal Birth Order Effect and the Genetics of Homosexuality.

Mathematicians have always been attracted to the field of genetics. The mathematical aspects of research on homosexuality are especially interesting. Certain studies show that male homosexuality may have a genetic component that is correlated with female fertility. Other studies show the existence of the fraternal birth order effect, that is, the correlation of homosexuality with the number of older brothers. This article is devoted to the mathematical aspects of how these two phenomena are interconnected. In particular, we show that the fraternal birth order effect implies a correlation between homosexuality and maternal fecundity. Vice versa, we show that the correlation between homosexuality and female fecundity implies the increase in the probability of the younger brothers being homosexual.

Rapid and complicated HIV genotype expansion among high-risk groups in Guangdong Province, China.

BACKGROUND: Guangdong Province is one of the most developed and populous provinces in southern China, with frequent foreign exchanges and large transient population. The annual number of cases of HIV/AIDS reported in Guangdong has been higher than most of provinces in China for several successive years. HIV infection by heterosexual transmission occurs across the province, with transmission among men who have sex with men occurring mainly in larger urban centers. There is a lack of widespread and representative data on the distribution of HIV subtypes in Guangdong. This study aimed to thoroughly investigate and estimate the prevalence and distribution of HIV-1 subtypes using a city-based sampling strategy to better understand the characteristics of HIV transmission in Guangdong. METHODS: Archived plasma samples (n = 1205) from individuals diagnosed as HIV-1 infection in 2013 were selected randomly from all 21 cities in Guangdong Province. Genotypes were determined using env and/or gag sequences using phylogenetic analysis. The distributions of HIV genotypes in different risk groups and different cities were analyzed. RESULTS: A total of 15 genotypes, including six discordant genotypes, were identified. The four main HIV-1 subtypes in Guangdong were CRF01_AE (43.2%), CRF07_BC (26.3%), CRF55_01B (8.5%), and CRF08_BC (8.4%). CRF01_AE was the predominant subtype in all risk populations. The high mobility of people shaped the complexity of the HIV genotypes, while the switch of risk factors affected the distribution and future trend of HIV-1 genotypes in Guangdong. Another epicenter located in the western region in addition to the known epicenter cities in the Pearl River Delta region of Guangdong may exist. CONCLUSIONS: Our study provides a comprehensive molecular epidemiologic dataset to understand the diversity and distribution of HIV genotypes in Guangdong, as well as to clarify the unique region- and risk group-specific transmission dynamics. The results provide critical and insightful information for more effective intervention strategies to limit HIV transmission in the future.

Biogenetic ties and parent-child relationships: The misplaced critique.

According to an almost axiomatic standard in bioethics, moral commitment should ground parents' relationship with their children, rather than biogenetic relatedness. This standard has been used lately to express skepticism about extending existing assisted reproductive treatments (ARTs) to same-sex couples and to research into novel fertility interventions for those couples, but this skepticism is misplaced on several grounds. As a matter of access and equity, same-sex couples seem presumptively entitled to genetic relatedness to their children as far as possible both in regard to existing ARTs and to novel ARTs under investigation. For those worried about the effects of trying to secure biogenetic relatedness for same-sex couples, it may be noted that same-sex couples will only ever be a fraction of the parents implicated in propping up "biologism," as the expectation of biogenetic relatedness it is sometimes called. The cultural force of biologism would survive almost intact even if no same-sex couples were ever to have genetically related children. It is therefore hard to see why same-sex couples should forfeit aspirations to biogenetic relationships with their children or enjoy less subsidy for ARTs than the subsidy given to different-sex couples. As matter of moral consistency, the full implications of the biologism critique have yet to be evaluated relative to different-sex couples.

No Substantial Evidence for Sexual Transmission of Minority HIV Drug Resistance Mutations in Men Who Have Sex with Men.

During primary HIV infection, the presence of minority drug resistance mutations (DRM) may be a consequence of sexual transmission, de novo mutations, or technical errors in identification. Baseline blood samples were collected from 24 HIV-infected antiretroviral-naive, genetically and epidemiologically linked source and recipient partners shortly after the recipient's estimated date of infection. An additional 32 longitudinal samples were available from 11 recipients. Deep sequencing of HIV reverse transcriptase (RT) was performed (Roche/454), and the sequences were screened for nucleoside and nonnucleoside RT inhibitor DRM. The likelihood of sexual transmission and persistence of DRM was assessed using Bayesian-based statistical modeling. While the majority of DRM (>20%) were consistently transmitted from source to recipient, the probability of detecting a minority DRM in the recipient was not increased when the same minority DRM was detected in the source (Bayes factor [BF] = 6.37). Longitudinal analyses revealed an exponential decay of DRM (BF = 0.05) while genetic diversity increased. Our analysis revealed no substantial evidence for sexual transmission of minority DRM (BF = 0.02). The presence of minority DRM during early infection, followed by a rapid decay, is consistent with the "mutation-selection balance" hypothesis, in which deleterious mutations are more efficiently purged later during HIV infection when the larger effective population size allows more efficient selection. Future studies using more recent sequencing technologies that are less prone to single-base errors should confirm these results by applying a similar Bayesian framework in other clinical settings.IMPORTANCE The advent of sensitive sequencing platforms has led to an increased identification of minority drug resistance mutations (DRM), including among antiretroviral therapy-naive HIV-infected individuals. While transmission of DRM may impact future therapy options for newly infected individuals, the clinical significance of the detection of minority DRM remains controversial. In the present study, we applied deep-sequencing techniques within a Bayesian hierarchical framework to a cohort of 24 transmission pairs to investigate whether minority DRM detected shortly after transmission were the consequence of (i) sexual transmission from the source, (ii) de novo emergence shortly after infection followed by viral selection and evolution, or (iii) technical errors/limitations of deep-sequencing methods. We found no clear evidence to support the sexual transmission of minority resistant variants, and our results suggested that minor resistant variants may emerge de novo shortly after transmission, when the small effective population size limits efficient purge by natural selection.

A Phylogenetic Analysis of Human Immunodeficiency Virus Type 1 Sequences in Kiev: Findings Among Key Populations.

Background: The human immunodeficiency virus (HIV) epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission. Methods: Protease and reverse transcriptase sequences from 876 new HIV diagnoses (April 2013-March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥2 sequences, ≥80% local branch support, and maximum genetic distance of all sequence pairs in the cluster ≤2.5%. Recent infection was determined through the limiting antigen avidity enzyme immunoassay. Sequences were analyzed for transmitted drug resistance mutations. Results: Thirty percent of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (odds ratio [OR], 4.38 [95% confidence interval {CI}, 2.56-7.50]); risk group (OR, 5.65 [95% CI, 3.27-9.75]) for men who have sex with men compared to heterosexual males; recent, compared to long-standing, infection (OR, 2.72 [95% CI, 1.64-4.52]); reported sex work contact (OR, 1.93 [95% CI, 1.07-3.47]); and younger age groups compared with age ≥36 years (OR, 1.83 [95% CI, 1.10-3.05] for age ≤25 years). Females were associated with lower odds of clustering than heterosexual males (OR, 0.49 [95% CI, .31-.77]). In multivariate analysis, risk group, subtype, and age group were independently associated with clustering (P < .001, P = .007, and P = .033, respectively). Eighteen sequences (2.1%) indicated evidence of transmitted drug resistance. Conclusions: Our findings suggest high levels of transmission and bridging between risk groups.

Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice.

Although the question of to whom a male directs his mating attempts is a critical one in social interactions, little is known about the molecular and cellular mechanisms controlling mammalian sexual preference. Here we report that the neurotransmitter 5-hydroxytryptamine (5-HT) is required for male sexual preference. Wild-type male mice preferred females over males, but males lacking central serotonergic neurons lost sexual preference although they were not generally defective in olfaction or in pheromone sensing. A role for 5-HT was demonstrated by the phenotype of mice lacking tryptophan hydroxylase 2 (Tph2), which is required for the first step of 5-HT synthesis in the brain. Thirty-five minutes after the injection of the intermediate 5-hydroxytryptophan (5-HTP), which circumvented Tph2 to restore 5-HT to the wild-type level, adult Tph2 knockout mice also preferred females over males. These results indicate that 5-HT and serotonergic neurons in the adult brain regulate mammalian sexual preference.

Low- and high-risk human papillomavirus genotype infections in intra-anal warts in HIV-positive men who have sex with men.

BACKGROUND: Anogenital warts are often presumed to represent nondysplastic or low-grade anal intraepithelial neoplasia (LGAIN). We previously demonstrated that up to 20% of intra-anal warts in HIV-positive men who have sex with men (MSM) contain regions of high-grade AIN (HGAIN). OBJECTIVES: To determine the causative human papillomavirus (HPV) types of low- and high- grade dysplastic areas in warts from HIV-positive MSM. METHODS: A total of 42 intra-anal warts from 41 HIV-positive MSM were graded as nondysplastic, LGAIN or HGAIN. Whole-tissue sections (WTS) were analysed with the SPF10 polymerase chain reaction/LiPA25 HPV genotyping system. If the WTS contained multiple HPV types, dysplastic regions were isolated by laser capture microdissection (LCM) for HPV genotyping. RESULTS: Overall, 38 of 42 (91%) WTS tested positive for HPV DNA. Of these, 23 (61%) contained a single HPV type and 15 (39%) contained multiple HPV types. All LCM-selected regions contained no more than one HPV type. Ten of 42 (24%) WTS contained HGAIN disease, of which six (60%) were associated with a high-risk HPV (hrHPV) genotype. Twenty-three of 42 WTS contained LGAIN disease, of which two (9%) were associated with hrHPV. AIN lesions containing hrHPV types were identified using p16 staining. CONCLUSIONS: LGAIN lesions can be caused by high-risk HPV genotypes and vice versa. We therefore recommend routine follow-up and treatment of all dysplastic intra-anal warts for HIV-positive MSM.

Hypersexual, Sexually Compulsive, or Just Highly Sexually Active? Investigating Three Distinct Groups of Gay and Bisexual Men and Their Profiles of HIV-Related Sexual Risk.

Emerging research supports the notion that sexual compulsivity (SC) and hypersexual disorder (HD) among gay and bisexual men (GBM) might be conceptualized as comprising three groups-Neither SC nor HD; SC only, and Both SC and HD-that capture distinct levels of severity across the SC/HD continuum. We examined data from 370 highly sexually active GBM to assess how the three groups compare across a range of risk factors for HIV infection. Comparisons focused on psychosexual measures-temptation for condomless anal sex (CAS), self-efficacy for avoiding CAS, sexual excitation and inhibition-as well as reports of actual sexual behavior. Nearly half (48.9 %) of this highly sexually active sample was classified as Neither SC nor HD, 30 % as SC Only, and 21.1 % as Both SC and HD. While we found no significant differences between the three groups on reported number of male partners, anal sex acts, or anal sex acts with serodiscordant partners, the Both SC and HD group reported higher numbers of CAS acts and CAS acts with serodiscordant partners and also had a higher proportion of their anal sex acts without condoms compared to the SC Only group. Our findings support the validity of a three-group classification system of SC/HD severity in differentiating psychosexual and HIV-related sexual risk behavior outcomes in a sample of GBM who report similarly high levels of sexual activity. Notwithstanding the need for sex positive HIV prevention programs, interventions that attempt to help Both SC and HD men deal with distress and address their psychosexual needs specifically may derive HIV prevention benefits.

Heterosexual Male Carriers Could Explain Persistence of Homosexuality in Men: Individual-Based Simulations of an X-Linked Inheritance Model.

Homosexuality has been documented throughout history and is found in almost all human cultures. Twin studies suggest that homosexuality is to some extent heritable. However, from an evolutionary perspective, this poses a problem: Male homosexuals tend to have on average five times fewer children than heterosexual males, so how can a phenomenon associated with low reproductive success be maintained at relatively stable frequencies? Recent findings of increased maternal fecundity of male homosexuals suggest that the genes responsible for homosexuality in males increase fecundity in the females who carry them. Can an increase in maternal fecundity compensate for the fecundity reduction in homosexual men and produce a stable polymorphism? In the current study, this problem was addressed with an individual-based modeling (IBM) approach. IBM suggests that male homosexuality can be maintained in a population at low and stable frequencies if roughly more than half of the females and half of the males are carriers of genes that predispose the male to homosexuality.

Lipids profile among ART-naïve HIV infected patients and men who have sex with men in China: a case control study.

BACKGROUND: Dyslipidemia is commonly seen in human immunodeficiency virus (HIV) infected patients. Understanding the risk factors of abnormal lipid profiles is urgent for proposing targeted approaches to prevention. Our objective was to assess the incidence and associated factors of abnormal lipid profiles and atherogenic index of plasma (AIP) among antiretroviral therapy (ART) naïve men who have sex with men (MSM) acute HIV infection (AHI) and chronic HIV infection (CHI) patients in China. METHODS: We compared lipids parameters such as triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and AIP between MSM HIV-infected patients and MSM HIV negative controls. Multivariable linear regression was used to evaluate risk factors of higher AIP. RESULTS: We performed a case control analysis of 110 AHI, 110 CHI and 100 HIV negative MSM participants. The TC, HDL-C and LDL-C levels were decreased in the AHI and CHI groups compared to the controls (3.90 ± 0.73 mmol/L and 3.72 ± 0.74 mmol/L versus 4.49 ± 0.91 mmol/L, p < 0.001; 1.00 ± 0.25 mmol/L and 1.01 ± 0.30 mmol/L versus 1.19 ± 0.29 mmol/L, p < 0.001; 2.11 ± 0.57 mmol/L and 2.22 ± 0.58 mmol/L versus 2.75 ± 0.78 mmol/L, p < 0.001). The AIP score was higher in the AHI patients compared to the control group [0.08 (-0.05-0.20) versus-0.04 (-0.21-0.22), p = 0.039]. In total groups, AIP was associated with AHI and TG positively (ß = 0.029 ± 0.012, p = 0.015;ß = 0.273 ± 0.009, p < 0.001) and correlated with HDL-C inversely (ß = -0.444 ± 0.023, p < 0.001). CONCLUSIONS: HIV infection contributed to decreased TC, LDL-C and HDL-C. AHI contributed to higher AIP level. An urgent need exists for earlier HIV diagnosis and better prevention of dyslipidemia in China.

[Research progress on molecular genetics of male homosexuality].

Sexual orientation is influenced by both environmental factors and biological factors. Family and twin studies have shown that genetic factors play an important role in the formation of male homosexuality. Genome-wide scan also revealed candidate chromosomal regions which may be associated with male homosexuality, but so far no clearly related genes have been found. This article reviews the progress of relevant studies and candidate genes which are related to male homosexuality.

Genome-wide scan demonstrates significant linkage for male sexual orientation.

BACKGROUND: Findings from family and twin studies support a genetic contribution to the development of sexual orientation in men. However, previous studies have yielded conflicting evidence for linkage to chromosome Xq28. METHOD: We conducted a genome-wide linkage scan on 409 independent pairs of homosexual brothers (908 analyzed individuals in 384 families), by far the largest study of its kind to date. RESULTS: We identified two regions of linkage: the pericentromeric region on chromosome 8 (maximum two-point LOD = 4.08, maximum multipoint LOD = 2.59), which overlaps with the second strongest region from a previous separate linkage scan of 155 brother pairs; and Xq28 (maximum two-point LOD = 2.99, maximum multipoint LOD = 2.76), which was also implicated in prior research. CONCLUSIONS: Results, especially in the context of past studies, support the existence of genes on pericentromeric chromosome 8 and chromosome Xq28 influencing development of male sexual orientation.

5-HTTLPR moderates naltrexone and psychosocial treatment responses in heavy drinking men who have sex with men.

BACKGROUND: A functional polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene has been widely studied as a risk factor and moderator of treatment for a variety of psychopathologic conditions. To evaluate whether 5-HTTLPR moderates the effects of treatment to reduce heavy drinking, we studied 112 high-functioning European-American men who have sex with men (MSM). Subjects participated in a randomized clinical trial of naltrexone (NTX) and cognitive behavioral therapy (CBT) for problem drinking. METHODS: Subjects were treated for 12 weeks with 100 mg/d of oral NTX or placebo (PBO). All participants received medical management with adjusted brief behavioral compliance enhancement treatment (BBCET) alone or in combination with modified behavioral self-control therapy (MBSCT; an amalgam of motivational interviewing and CBT). Participants were genotyped for the tri-allelic 5-HTTLPR polymorphism (i.e., low-activity S' or high-activity L' alleles). RESULTS: During treatment, the number of weekly heavy drinking days (HDD; defined as 5 or more standard drinks per day) was significantly lower in subjects with the L'L' (N = 26, p = 0.015) or L'S' (N = 52, p = 0.016) genotype than those with the S'S' (N = 34) genotype regardless of treatment type. There was a significant interaction of genotype with treatment: For subjects with the S'S' genotype, the effects of MBSCT or NTX on HDD were significantly greater than the minimal intervention (i.e., BBCET or PBO, p = 0.007 and p = 0.049, respectively). In contrast, for subjects with 1 or 2 L' alleles, the effects of the more intensive psychosocial treatment (MBSCT) or NTX did not significantly differ from BBCET or PBO. CONCLUSIONS: These preliminary findings support the utility of the 5-HTTLPR polymorphism for personalizing treatment selection in problem drinkers.