Publications

2011
Haig D. Genomic imprinting and the evolutionary psychology of human kinship. Proc Natl Acad Sci USA. 2011;108 Suppl 2 :10878-85.Abstract

Genomic imprinting is predicted to influence behaviors that affect individuals to whom an actor has different degrees of matrilineal and patrilineal kinship (asymmetric kin). Effects of imprinted genes are not predicted in interactions with nonrelatives or with individuals who are equally related to the actor's maternally and paternally derived genes (unless a gene also has pleiotropic effects on fitness of asymmetric kin). Long-term mating bonds are common in most human populations, but dissolution of marriage has always affected a significant proportion of mated pairs. Children born in a new union are asymmetric kin of children born in a previous union. Therefore, the innate dispositions of children toward parents and sibs are expected to be sensitive to cues of marital stability, and these dispositions may be subject to effects of imprinted genes.

pnas-2011-haig-10878-85.pdf
Ubeda F, Haig D, Patten MM. Stable linkage disequilibrium owing to sexual antagonism. Proc Biol Sci. 2011;278 :855-62.Abstract

Linkage disequilibrium (LD) is an association between genetic loci that is typically transient. Here, we identify a previously overlooked cause of stable LD that may be pervasive: sexual antagonism. This form of selection produces unequal allele frequencies in males and females each generation, which upon admixture at fertilization give rise to an excess of haplotypes that couple male-beneficial with male-beneficial and female-beneficial with female-beneficial alleles. Under sexual antagonism, LD is obtained for all recombination frequencies in the absence of epistasis. The extent of LD is highest at low recombination and for stronger selection. We provide a partition of the total LD into distinct components and compare our result for sexual antagonism with Li and Nei's model of LD owing to population subdivision. Given the frequent observation of sexually antagonistic selection in natural populations and the number of traits that are often involved, these results suggest a major contribution of sexual antagonism to genomic structure.

855.full_.pdf
Haig D. Sympathy with Adam Smith and reflexions on self. J Econ Behav Org. 2011;77 (1) :4-13. 1-s2.0-s0167268110001721-main.pdf
2010
Haig D. Colloquium papers: Transfers and transitions: parent-offspring conflict, genomic imprinting, and the evolution of human life history. Proc Natl Acad Sci USA. 2010;107 Suppl 1 :1731-5.Abstract

Human offspring are weaned earlier than the offspring of other great apes but take longer to reach nutritional independence. An analysis of human disorders of imprinted genes suggests genes of paternal origin, expressed in infants, have been selected to favor more intense suckling than genes of maternal origin. The same analysis suggests that genes of maternal origin may favor slower childhood growth but earlier sexual maturation. These observations are consistent with a hypothesis in which slow maturation was an adaptation of offspring that reduced maternal fitness, whereas early weaning was an adaptation of mothers that reduced the fitness of individual offspring.

pnas-2010-haig-1731-5.pdf
Patten MM, Haig D, Ubeda F. Fitness variation due to sexual antagonism and linkage disequilibrium. Evolution. 2010;64 :3638-42.Abstract

Extensive fitness variation for sexually antagonistic characters has been detected in nature. However, current population genetic theory suggests that sexual antagonism is unlikely to play a major role in the maintenance of variation. We present a two-locus model of sexual antagonism that is capable of explaining greater fitness variance at equilibrium than previous single-locus models. The second genetic locus provides additional fitness variance in two complementary ways. First, linked loci can maintain gene variants that are lost in single-locus models of evolution, expanding the opportunity for polymorphism. Second, linkage disequilibrium results between any two sexually antagonistic genes, producing an excess of high- and low-fitness haplotypes. Our results uncover a unique contribution of conflicting selection pressures to the maintenance of variation, which simpler models that neglect genetic architecture overlook.

patten_et_al-2010-evolution.pdf
Haig D. Games in tetrads: segregation, recombination, and meiotic drive. Am Nat. 2010;176 :404-13.Abstract

The two alleles at a heterozygous locus segregate during meiosis, sometimes at meiosis I and sometimes at meiosis II. The timing of segregation is determined by the pattern of crossing-over between a locus and its attached centromeres. Genes near centromeres can exploit this process by driving against spores from which the genes separated at meiosis I. Other genes, located distal to centromeres, can benefit from driving against spores from which they separated at meiosis II. Asymmetric female meiosis is particularly susceptible to such forms of drive. Selection on modifiers of recombination favors changes in the location of chiasmata that increase the proportion of tetrads of high average fitness by changing the timing of segregation. Such changes increase the frequency of driving alleles. This source of selection on recombination does not depend on effects on linkage disequilibrium. Recombinational responses to meiotic drive may contribute to sex differences in overall recombination and sex differences in the localization of chiasmata.

656265.pdf
Gregg C, Zhang J, Weissbourd B, Luo S, Schroth GP, Haig D, Dulac C. High-resolution analysis of parent-of-origin allelic expression in the mouse brain. Science. 2010;329 :643-8.Abstract

Genomic imprinting results in preferential expression of the paternal or maternal allele of certain genes. We have performed a genome-wide characterization of imprinting in the mouse embryonic and adult brain. This approach uncovered parent-of-origin allelic effects of more than 1300 loci. We identified parental bias in the expression of individual genes and of specific transcript isoforms, with differences between brain regions. Many imprinted genes are expressed in neural systems associated with feeding and motivated behaviors, and parental biases preferentially target genetic pathways governing metabolism and cell adhesion. We observed a preferential maternal contribution to gene expression in the developing brain and a major paternal contribution in the adult brain. Thus, parental expression bias emerges as a major mode of epigenetic regulation in the brain.

science-2010-gregg-643-8.pdf
Gregg C, Zhang J, Butler JE, Haig D, Dulac C. Sex-specific parent-of-origin allelic expression in the mouse brain. Science. 2010;329 :682-5.Abstract

Genomic imprinting results in preferential gene expression from paternally versus maternally inherited chromosomes. We used a genome-wide approach to uncover sex-specific parent-of-origin allelic effects in the adult mouse brain. Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex. Moreover, analysis of the cortex and hypothalamus identified 347 autosomal genes with sex-specific imprinting features. In the hypothalamus, sex-specific imprinted genes were mostly found in females, which suggests parental influence over the hypothalamic function of daughters. We show that interleukin-18, a gene linked to diseases with sex-specific prevalence, is subject to complex, regional, and sex-specific parental effects in the brain. Parent-of-origin effects thus provide new avenues for investigation of sexual dimorphism in brain function and disease.

science-2010-gregg-682-5.pdf
Ubeda F, Haig D, Patten MM. Stable linkage disequilibrium owing to sexual antagonism. Proc Roy Soc Biol Sci. 2010;278 (1707) :855-862. 855.full_1.pdf
Haig D. What do we know about charophyte (streptophyta) life cycles?. J Phycol. 2010;46 (5) :860-867. haig-2010-journal_of_phycology.pdf
2009
Papper Z, Jameson NM, Romero R, Weckle AL, Mittal P, Benirschke K, Santolaya-Forgas J, Uddin M, Haig D, Goodman M, et al. Ancient origin of placental expression in the growth hormone genes of anthropoid primates. Proc Natl Acad Sci USA. 2009;106 :17083-8.Abstract

In anthropoid primates, growth hormone (GH) genes have undergone at least 2 independent locus expansions, one in platyrrhines (New World monkeys) and another in catarrhines (Old World monkeys and apes). In catarrhines, the GH cluster has a pituitary-expressed gene called GH1; the remaining GH genes include placental GHs and placental lactogens. Here, we provide cDNA sequence evidence that the platyrrhine GH cluster also includes at least 3 placenta expressed genes and phylogenetic evidence that placenta expressed anthropoid GH genes have undergone strong adaptive evolution, whereas pituitary-expressed GH genes have faced strict functional constraint. Our phylogenetic evidence also points to lineage-specific gene gain and loss in early placental mammalian evolution, with at least three copies of the GH gene present at the time of the last common ancestor (LCA) of primates, rodents, and laurasiatherians. Anthropoid primates and laurasiatherians share gene descendants of one of these three copies, whereas rodents and strepsirrhine primates each maintain a separate copy. Eight of the amino-acid replacements that occurred on the lineage leading to the LCA of extant anthropoids have been implicated in GH signaling at the maternal-fetal interface. Thus, placental expression of GH may have preceded the separate series of GH gene duplications that occurred in catarrhines and platyrrhines (i.e., the roles played by placenta-expressed GHs in human pregnancy may have a longer evolutionary history than previously appreciated).

pnas-2009-papper-17083-8.pdf
Patten MM, Haig D. Maintenance or loss of genetic variation under sexual and parental antagonism at a sex-linked locus. Evolution. 2009;63 :2888-95.Abstract

An intralocus genetic conflict occurs when a locus is selected in opposing directions in different subsets of a population. Populations with two sexes have the potential to host a pair of distinct intralocus conflicts: sexual antagonism and parental antagonism. In this article, we examine the population genetic consequences of these conflicts for X-linked genes. Both conflicts are capable of maintaining genetic variation in a population, but to different degrees. For weak sexual antagonism, the X chromosome has a higher opportunity for polymorphism than the autosomes. For parental antagonism, there is a very limited opportunity for polymorphism on the X chromosome relative to autosomes or to sexual antagonism. X-linkage introduces an asymmetry in the inheritance and expression of sexually and parentally antagonistic genes that leads to a biased fixation of alleles with certain effects. We find little support for the commonly held intuition that the X chromosome should be biased toward fixing female-beneficial alleles. Contrary to this intuition, we find that the X chromosome is biased toward fixation of male-beneficial alleles for much of the range of dominance. Additionally, we find that the X chromosome is more favorable to the fixation of alleles that are beneficial when maternally derived.

evolution_63_11_2888-2895.pdf
Patten MM, Haig D. Parental sex discrimination and intralocus sexual conflict. Biol Lett. 2009;5 :667-70.Abstract

Intralocus sexual conflict occurs when populations segregate for alleles with opposing fitness consequences in the two sexes. This form of selection is known to be capable of maintaining genetic and fitness variation in nature, the extent of which is sensitive to the underlying genetics. We present a one-locus model of a haploid maternal effect that has sexually antagonistic consequences for offspring. The evolutionary dynamics of these maternal effects are distinct from those of haploid direct effects under sexual antagonism because the relevant genes are expressed only in females. Despite this, we find the same opportunity for sexually antagonistic polymorphism at the maternal effect locus as at a direct effect locus. Thus, sexually antagonistic maternal effects may underlie some natural genetic variation. The model we present permits alternative interpretations of how the genes are expressed and how the fitness variation is assigned, which invites a theoretical comparison to models of both imprinted genes and sex allocation.

667.full_.pdf
2008
Karumanchi SA, Haig D. Flt1, pregnancy, and malaria: evolution of a complex interaction. Proc Natl Acad Sci USA. 2008;105 :14243-4. pnas-2008-karumanchi-14243-4.pdf
Haig D. Homologous versus antithetic alternation of generations and the origin of sporophytes. Bot Rev. 2008;74 (3) :395. art3a10.10072fs12229-008-9012-x.pdf
Haig D. Huddling: brown fat, genomic imprinting and the warm inner glow. Curr Biol. 2008;18 :R172-4.Abstract

Heat generated by huddling animals is a public good with a private cost and thus vulnerable to exploitation, as illustrated by recent work on rabbits and penguins. Effects of imprinted genes on brown adipose tissue suggest that non-shivering thermogenesis is an arena for intragenomic conflict.

1-s2.0-s0960982207024372-main.pdf
Haig D. Kinship asymmetries and the divided self. Behv Brain Sci. 2008;31 :271-272. s0140525x08004329a.pdf
Haig D. Placental growth hormone-related proteins and prolactin-related proteins. Placenta. 2008;29 Suppl A :S36-41.Abstract

The placentas of ruminants and muroid rodents express prolactin (PRL)-related genes whereas the placentas of anthropoid primates express growth hormone (GH)-related genes. The evolution of placental expression is associated with accelerated evolution of the corresponding pituitary hormone and destabilization of conserved endocrine systems. In particular, placental hormones often evolve novel interactions with new receptors. The adaptive functions of some placental hormones may be revealed only under conditions of physiological stress.

placenta_29_supplement_a_trophoblast_research_vol._22_2008_s36es4.pdf
Patten MM, Haig D. Reciprocally imprinted genes and the response to selection on one sex. Genetics. 2008;179 :1389-94.Abstract

We explore the theoretical consequences of limiting selection to males for the evolution of imprinted genes. We find that the efficiency of male-limited selection depends on the pattern of imprinting at an imprinted locus. When selection is strong, the maternally expressed pattern of imprinting allows faster genetic change than the reciprocal, paternally expressed pattern. When selection is relatively weak, the pattern of imprinting that permits a greater rate of genetic response to selection depends on the frequency of the favored allele: the paternally expressed pattern permits faster genetic change than does the maternally expressed pattern at low frequencies of a favored allele; at higher frequencies of a favored allele, however, the maternally expressed pattern is again more conducive to a genetic response. To our knowledge, this is the first theoretical description of a difference between the two reciprocal patterns of imprinting. The selective efficiency bias we identify between the two patterns of imprinting has implications for natural and livestock populations, which we discuss.

gsa_2008.pdf
Engelstadter J, Haig D. Sexual antagonism and the evolution of X chromosome inactivation. Evolution. 2008;62 :2097-104.Abstract

In most female mammals, one of the two X chromosomes is inactivated early in embryogenesis. Expression of most genes on this chromosome is shut down, and the inactive state is maintained throughout life in all somatic cells. It is generally believed that X-inactivation evolved as a means of achieving equal gene expression in males and females (dosage compensation). Following degeneration of genes on the Y chromosome, gene expression on X chromosomes in males and females is upregulated. This results in closer to optimal gene expression in males, but deleterious overexpression in females. In response, selection is proposed to favor inactivation of one of the X chromosomes in females, restoring optimal gene expression. Here, we make a first attempt at shedding light on this intricate process from a population genetic perspective, elucidating the sexually antagonistic selective forces involved. We derive conditions for the process to work and analyze evolutionary stability of the system. The implications of our results are discussed in the light of empirical findings and a recently proposed alternative hypothesis for the evolution of X-inactivation.

engelst-dter_et_al-2008-evolution.pdf

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