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.

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.

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.

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.

Yano K, Gale D, Massberg S, Cheruvu PK, Monahan-Earley R, Morgan ES, Haig D, von Andrian UH, Dvorak AM, Aird WC. Phenotypic heterogeneity is an evolutionarily conserved feature of the endothelium. Blood. 2007;109 :613-5.Abstract

Mammalian endothelial cells (ECs) display marked phenotypic heterogeneity. Little is known about the evolutionary mechanisms underlying EC heterogeneity. The last common ancestor of hagfish and gnathostomes was also the last common ancestor of all extant vertebrates, which lived some time more than 500 million years ago. Features of ECs that are shared between hagfish and gnathostomes can be inferred to have already been present in this ancestral vertebrate. The goal of this study was to determine whether the hagfish endothelium displays phenotypic heterogeneity. Electron microscopy of the aorta, dermis, heart, and liver revealed ultrastructural heterogeneity of the endothelium. Immunofluorescent studies demonstrated marked differences in lectin binding between vascular beds. Intravital microscopy of the dermis revealed histamine-induced adhesion of leukocytes in capillaries and postcapillary venules, but no such adhesion in arterioles. Together, these data suggest that structural, molecular, and functional heterogeneity of the endothelium evolved as an early feature of this cell lineage.

Haig D. Weismann rules! OK? Epigenetics and the Lamarckian temptation. Biol Philos. 2007;22 :415-428. 07weismann.pdf
Haig D. Congenital bilateral absence of the vas deferens and recombination at CFTR. Eur J Hum Genet. 2006;14 :801; author reply 801. 5201622a.pdf
Haig D, Westoby M. An earlier formulation of the genetic conflict hypothesis of genomic imprinting. Nat Genet. 2006;38 :271. ng0306-271.pdf
Haig D. Intragenomic politics. Cytogenet Genome Res. 2006;113 :68-74.Abstract

The mammalian genome contains multiple genetic factions with distinct interests in the outcomes of interactions among kin. In the context of an offspring's relations with its mother, these factions are proposed to align into two 'parties', one favoring increased demand by offspring and the other favoring reduced demand. A possible alignment has inhibitors of demand located on the X chromosome and enhancers of demand located on autosomes, because X-linked loci are maternally derived two-thirds of the time by contrast to autosomal loci which are maternally derived half of the time.

Haig D. Self-imposed silence: parental antagonism and the evolution of X-chromosome inactivation. Evolution. 2006;60 :440-7.Abstract

A model is proposed for the evolution of X-chromosome inactivation (XCI) in which natural selection initially favors the silencing of paternally derived alleles of X-linked demand inhibitors. The compensatory upregulation of maternally derived alleles establishes a requirement for monoallelic expression in females. For this reason, XCI is self-reinforcing once established. However, inactivation of a particular X chromosome is not. Random XCI (rXCI) is favored over paternal XCI because rXCI reduces the costs of functional hemizygosity in females. Once present, rXCI favors the evolution of locus-by-locus imprinting of X-linked loci, which creates an evolutionary dynamic in which different chromosomes compete to remain active.

Haig D, Wilczek A. Sexual conflict and the alternation of haploid and diploid generations. Philos Trans R Soc Lond B Biol Sci. 2006;361 :335-43.Abstract

Land plants possess a multicellular diploid stage (sporophyte) that begins development while attached to a multicellular haploid progenitor (gametophyte). Although the closest algal relatives of land plants lack a multicellular sporophyte, they do produce a zygote that grows while attached to the maternal gametophyte. The diploid offspring shares one haploid set of genes with the haploid mother that supplies it with resources and a paternal haploid complement that is not shared with the mother. Sexual conflict can arise within the diploid offspring because the offspring's maternal genome will be transmitted in its entirety to all other sexual and asexual offspring that the mother may produce, but the offspring's paternally derived genes may be absent from these other offspring. Thus, the selective forces favouring the evolution of genomic imprinting may have been present from the origin of modern land plants. In bryophytes, where gametophytes are long-lived and capable of multiple bouts of asexual and sexual reproduction, we predict strong sexual conflict over allocation to sporophytes. Female gametophytes of pteridophytes produce a single sporophyte and often lack means of asexual reproduction. Therefore, sexual conflict is predicted to be attenuated. Finally, we explore similarities among models of mate choice, offspring choice and segregation distortion.

Yuan HT, Haig D, Ananth Karumanchi S. Angiogenic factors in the pathogenesis of preeclampsia. Curr Top Dev Biol. 2005;71 :297-312.Abstract

Preeclampsia affects 5-10% of pregnancies and is responsible for substantial maternal and neonatal morbidity and mortality. It is believed to be a two-stage disease with an initial placental trigger with no maternal symptoms followed by a maternal syndrome characterized by hypertension, proteinuria, and endothelial dysfunction. The first stage is thought to be due to shallow cytotrophoblast invasion of maternal spiral arterioles leading to placental insufficiency. The diseased placenta in turn releases soluble angiogenic factors that induce systemic endothelial dysfunction and clinical preeclampsia during the second stage. This review will discuss the role of circulating angiogenic factors of placental origin as potential mediators of the systemic endothelial dysfunction and the clinical syndrome of preeclampsia and provide an evolutionary explanation for this phenomenon.

Haig D. The complex history of distal human chromosome 1q. Genomics. 2005;86 :767-70.Abstract

Human chromosome 1 has been claimed to be a conserved ancestral chromosome of eutherian mammals. However, two small regions from distal 1q (with orthology to mouse chromosome 11) appear to have a different history. These two regions are proposed to have been added to the ancestor of human chromosome 1 as a single block that was subsequently disrupted by a paracentric inversion. The translocation and inversion appear to have occurred at some time after the primate lineage diverged from a common ancestor with rodents. Reconstruction of the history of distal human chromosome 1q is complicated by the "reuse" of breakpoints in different mammalian lineages and by coincidental shared synteny between humans and cats.

Brandvain Y, Haig D. Divergent mating systems and parental conflict as a barrier to hybridization in flowering plants. Am Nat. 2005;166 :330-8.Abstract

Parental conflicts can lead to antagonistic coevolution of the sexes and of parental genomes. Within a population, the resulting antagonistic effects should balance, but crosses between populations can reveal conflict. Parental conflict is less intense in self-pollinating plants than in outcrossers because outcrossing plants are pollinated by multiple pollen donors unrelated to the seed parent, while a self-pollinating plant is primarily pollinated by one individual (itself). Therefore, in crosses between plants with differing mating systems, outcrossing parents are expected to "overpower" selfing parents. We call this the weak inbreeder/strong outbreeder (WISO) hypothesis. Prezygotically, such overpowering can alter pollination success, and we argue that our hypothesis explains a common pattern of unilateral incompatibility, in which pollen from self-incompatible populations fertilizes ovules of self-compatible individuals but the reciprocal cross fails. A postzygotic manifestation of overpowering is aberrant seed development due to parent-of-origin effects such as genomic imprinting. We evaluate evidence for the WISO hypothesis by reviewing published accounts of crosses between plants of different mating systems. Many, but not all, of such reports support our hypothesis. Since parental conflicts can perturb fertilization and development, such conflicts may strengthen reproductive barriers between populations, contributing to speciation.

Ubeda F, Haig D. On the evolutionary stability of Mendelian segregation. Genetics. 2005;170 :1345-57.Abstract

We present a model of a primary locus subject to viability selection and an unlinked locus that causes sex-specific modification of the segregation ratio at the primary locus. If there is a balanced polymorphism at the primary locus, a population undergoing Mendelian segregation can be invaded by modifier alleles that cause sex-specific biases in the segregation ratio. Even though this effect is particularly strong if reciprocal heterozygotes at the primary locus have distinct viabilities, as might occur with genomic imprinting, it also applies if reciprocal heterozygotes have equal viabilities. The expected outcome of the evolution of sex-specific segregation distorters is all-and-none segregation schemes in which one allele at the primary locus undergoes complete drive in spermatogenesis and the other allele undergoes complete drive in oogenesis. All-and-none segregation results in a population in which all individuals are maximally fit heterozygotes. Unlinked modifiers that alter the segregation ratio are unable to invade such a population. These results raise questions about the reasons for the ubiquity of Mendelian segregation.

Mix LJ, Haig D, Cavanaugh CM. Phylogenetic analyses of the core antenna domain: investigating the origin of photosystem I. J Mol Evol. 2005;60 :153-63.Abstract

Phototrophy, the conversion of light to biochemical energy, occurs throughout the Bacteria and plants, however, debate continues over how different phototrophic mechanisms and the bacteria that contain them are related. There are two types of phototrophic mechanisms in the Bacteria: reaction center type 1 (RC1) has core and core antenna domains that are parts of a single polypeptide, whereas reaction center type 2 (RC2) is composed of short core proteins without antenna domains. In cyanobacteria, RC2 is associated with separate core antenna proteins that are homologous to the core antenna domains of RC1. We reconstructed evolutionary relationships among phototrophic mechanisms based on a phylogeny of core antenna domains/proteins. Core antenna domains of 46 polypeptides were aligned, including the RC1 core proteins of heliobacteria, green sulfur bacteria, and photosystem I (PSI) of cyanobacteria and plastids, plus core antenna proteins of photosystem II (PSII) from cyanobacteria and plastids. Maximum likelihood, parsimony, and neighbor joining methods all supported a single phylogeny in which PSII core antenna proteins (PsbC, PsbB) arose within the cyanobacteria from duplications of the RC1-associated core antenna domains and accessory antenna proteins (IsiA, PcbA, PcbC) arose from duplications of PsbB. The data indicate an evolutionary history of RC1 in which an initially homodimeric reaction center was vertically transmitted to green sulfur bacteria, heliobacteria, and an ancestor of cyanobacteria. A heterodimeric RC1 (=PSI) then arose within the cyanobacterial lineage. In this scenario, the current diversity of core antenna domains/proteins is explained without a need to invoke horizontal transfer.

Lukhtanov VA, Kandul NP, Plotkin JB, Dantchenko AV, Haig D, Pierce NE. Reinforcement of pre-zygotic isolation and karyotype evolution in Agrodiaetus butterflies. Nature. 2005;436 :385-9.Abstract

The reinforcement model of evolution argues that natural selection enhances pre-zygotic isolation between divergent populations or species by selecting against unfit hybrids or costly interspecific matings. Reinforcement is distinguished from other models that consider the formation of reproductive isolation to be a by-product of divergent evolution. Although theory has shown that reinforcement is a possible mechanism that can lead to speciation, empirical evidence has been sufficiently scarce to raise doubts about the importance of reinforcement in nature. Agrodiaetus butterflies (Lepidoptera: Lycaenidae) exhibit unusual variability in chromosome number. Whereas their genitalia and other morphological characteristics are largely uniform, different species vary considerably in male wing colour, and provide a model system to study the role of reinforcement in speciation. Using comparative phylogenetic methods, we show that the sympatric distribution of 15 relatively young sister taxa of Agrodiaetus strongly correlates with differences in male wing colour, and that this pattern is most likely the result of reinforcement. We find little evidence supporting sympatric speciation: rather, in Agrodiaetus, karyotypic changes accumulate gradually in allopatry, prompting reinforcement when karyotypically divergent races come into contact.

Haig D, Henikoff S. Deciphering the genomic palimpsest. Curr Opin Gen Dev. 2004;14 :599-602. 1-s2.0-s0959437x04001595-main.pdf
Haig D. The (dual) origin of epigenetics. Cold Spring Harb Symp Quant Biol. 2004;69 :67-70. cold_spring_harb_symp_quant_biol-2004-haig-sqb.2004.69.67.pdf