Haig D. Evolutionary conflicts in pregnancy and calcium metabolism--a review. Placenta. 2004;25 Suppl A :S10-5.Abstract

The maternal-fetal unit contains three distinct haplotypes at each locus: the maternally derived fetal haplotype (MDFH) that is shared by the mother and fetus, the paternally derived fetal haplotype (PDFH), and the non-inherited maternal haplotype (NIMH). The evolutionary forces acting on these haplotypes are distinct. The NIMH is absent from the offspring and could benefit from early abortion if this enhances the probability of the mother conceiving again and producing an offspring that inherits the NIMH. This raises the possibility that some forms of recurrent spontaneous abortion may be caused by non-inherited haplotypes. Such 'selfish' behaviour would be opposed by other components of the maternal genome. Natural selection acting on genes expressed in fetuses (or their placentae) favours greater maternal investment in the fetus than does natural selection acting on genes expressed in mothers. Furthermore, in the presence of genomic imprinting, the PDFH favours greater levels of investment in the fetus than does the MDFH. These conflicts are illustrated using the example of maternal-fetal conflicts over the supply of calcium. Inactivation of the paternal copy of GNAS in proximal renal tubule is interpreted as a measure to maintain fetal bone mineralization in times of calcium stress at the expense of the maternal skeleton.

Haig D. Genomic imprinting and kinship: how good is the evidence?. Annu Rev Genet. 2004;38 :553-85.Abstract

The kinship theory of genomic imprinting proposes that parent-specific gene expression evolves at a locus because a gene's level of expression in one individual has fitness effects on other individuals who have different probabilities of carrying the maternal and paternal alleles of the individual in which the gene is expressed. Therefore, natural selection favors different levels of expression depending on an allele's sex-of-origin in the previous generation. This review considers the strength of evidence in support of this hypothesis for imprinted genes in four "clusters," associated with the imprinted loci Igf2, Igf2r, callipyge, and Gnas. The clusters associated with Igf2 and Igf2r both contain paternally expressed transcripts that act as enhancers of prenatal growth and maternally expressed transcripts that act as inhibitors of prenatal growth. This is consistent with predictions of the kinship theory. However, the clusters also contain imprinted genes whose phenotypes as yet remain unexplained by the theory. The principal effects of imprinted genes in the callipyge and Gnas clusters appear to involve lipid and energy metabolism. The kinship theory predicts that maternally expressed transcripts will favor higher levels of nonshivering thermogenesis (NST) in brown adipose tissue (BAT) of animals that huddle for warmth as offspring. The phenotypes of reciprocal heterozygotes for Gnas knockouts provide provisional support for this hypothesis, as does some evidence from other imprinted genes (albeit more tentatively). The diverse effects of imprinted genes on the development of white adipose tissue (WAT) have so far defied a unifying hypothesis in terms of the kinship theory.

Haig D. The inexorable rise of gender and the decline of sex: social change in academic titles, 1945-2001. Arch Sex Behav. 2004;33 :87-96.Abstract

More than 30 million titles of "academic" articles, from the years 1945-2001, were surveyed for occurrences of the words sex and gender. At the beginning of this period, uses of gender were much rarer than uses of sex, and often used in the sense of a grammatical category. By the end of this period, uses of gender outnumbered uses of sex in the social sciences, arts, and humanities. Within the natural sciences, there was now more than 1 use of gender for every 2 uses of sex. The beginnings of this change in usage can be traced to Money's introduction of the concept of "gender role" in 1955 (J. Money, 1955). However, the major expansion in the use of gender followed its adoption by feminists to distinguish the social and cultural aspects of differences between men and women (gender) from biological differences (sex). Since then, the use of gender has tended to expand to encompass the biological, and a sex/gender distinction is now only fitfully observed.

Kandul NP, Lukhtanov VA, Dantchenko AV, Coleman JW, Sekercioglu CH, Haig D, Pierce NE. Phylogeny of Agrodiaetus Hubner 1822 (Lepidoptera: Lycaenidae) inferred from mtDNA sequences of COI and COII and nuclear sequences of EF1-alpha: karyotype diversification and species radiation. Syst Biol. 2004;53 :278-98.Abstract

Butterflies in the large Palearctic genus Agrodiaetus (Lepidoptera: Lycaenidae) are extremely uniform and exhibit few distinguishing morphological characters. However, these insects are distinctive in one respect: as a group they possess among the greatest interspecific karyotype diversity in the animal kingdom, with chromosome numbers (n) ranging from 10 to 125. The monophyly of Agrodiaetus and its systematic position relative to other groups within the section Polyommatus have been controversial. Characters from the mitochondrial genes for cytochrome oxidases I and II and from the nuclear gene for elongation factor 1 alpha were used to reconstruct the phylogeny of Agrodiaetus using maximum parsimony and Bayesian phylogenetic methods. Ninety-one individuals, encompassing most of the taxonomic diversity of Agrodiaetus, and representatives of 14 related genera were included in this analysis. Our data indicate that Agrodiaetus is monophyletic. Representatives of the genus Polyommatus (sensu stricto) are the closest relatives. The sequences of the Agrodiaetus taxa in this analysis are tentatively arranged into 12 clades, only 1 of which corresponds to a species group traditionally recognized in Agrodiaetus. Heterogeneous substitution rates across a recovered topology were homogenized with a nonparametric rate-smoothing algorithm before the application of a molecular clock. Two published estimates of substitution rates dated the origin of Agrodiaetus between 2.51 and 3.85 million years ago. During this time, there was heterogeneity in the rate and direction of karyotype evolution among lineages within the genus. Karyotype instability has evolved independently three times in the section Polyommatus, within the lineages Agrodiaetus, Lysandra, and Plebicula. Rapid karyotype diversification may have played a significant role in the radiation of the genus Agrodiaetus.

Ubeda F, Haig D. Sex-specific meiotic drive and selection at an imprinted locus. Genetics. 2004;167 :2083-95.Abstract

We present a one-locus model that breaks two symmetries of Mendelian genetics. Whereas symmetry of transmission is breached by allowing sex-specific segregation distortion, symmetry of expression is breached by allowing genomic imprinting. Simple conditions for the existence of at least one polymorphic stable equilibrium are provided. In general, population mean fitness is not maximized at polymorphic equilibria. However, mean fitness at a polymorphic equilibrium with segregation distortion may be higher than mean fitness at the corresponding equilibrium with Mendelian segregation if one (or both) of the heterozygote classes has higher fitness than both homozygote classes. In this case, mean fitness is maximized by complete, but opposite, drive in the two sexes. We undertook an extensive numerical analysis of the parameter space, finding, for the first time in this class of models, parameter sets yielding two stable polymorphic equilibria. Multiple equilibria exist both with and without genomic imprinting, although they occurred in a greater proportion of parameter sets with genomic imprinting.

Haig D. The amoral roots of morality. Lahey Clinic Medical Ethics. 2003;10 (3) :10-11.
Haig D. The science that dare not speak its name. Quarterly Review of BIology. 2003;78 :327-335.
Haig D. Behavioural genetics: Family matters. Nature. 2003;421 :491-2. 421491a.pdf
Ubeda F, Haig D. Dividing the child. Genetica. 2003;117 :103-10.Abstract

The evolution of genomic imprinting is viewed as a problem of economic optimization that is analyzed using the tools of evolutionary game theory. We specifically consider genetic conflicts over the allocation of maternal resources between present and future offspring. Five sets of genes, with the same interests within sets but distinct interests between sets, are considered as agents: maternal alleles (Mater), paternal alleles (Pater), unimprinted offspring alleles (Filius), and imprinted offspring alleles of maternal and paternal origin (Matris and Patris). Fitness functions are derived for each agent and the parameter space in which there is conflict defined. Three potential conflicts are considered: between mother and offspring (Mater v.s. Filius); between alleles of maternal and paternal origin within offspring (Matris v.s. Patris) and between mothers and the paternally derived alleles of offspring (Mater v.s. Patris).

Wilkins JF, Haig D. Inbreeding, maternal care and genomic imprinting. J Theor Biol. 2003;221 :559-64.Abstract

Inactivation of expression of the paternal allele at two maternally silent imprinted loci has recently been reported to diminish the quality of care that female mice lavish on their offspring. This suggests that there can be disagreement between the maternally and paternally derived genomes of mothers over how much care for offspring is appropriate, with the paternally derived genome favoring greater care. The reason for such disagreement is not obvious because the maternally and paternally derived alleles at a locus have equal probabilities of being transmitted to each of the mother's ova and, therefore, would appear to have equal interests in a mother's offspring. However, if a female mates with a related male, her two alleles may have different probabilities of being present in the sperm that fertilize her ova. Natural selection can favor silencing of the maternally derived allele at a locus that enhances the quality of maternal care if the average patrilineal relatedness between a female and her mates decreases more rapidly than the average matrilineal relatedness. Just such an asymmetrical decrease in relatedness over time would be expected in a structured population in which patrilineal inbreeding is more common than matrilineal inbreeding.

Haig D. On intrapersonal reciprocity. Evol Human Behav. 2003;24 :418-425.
Haig D. Meditations on birth weight: is it better to reduce the variance or increase the mean?. Epidemiology. 2003;14 :490-2.Abstract

A conceptual model is presented here in which the birth weight distribution is decomposed into a distribution of target weights and a distribution of perturbations from the target. The target weight is the adaptive goal of fetal development. In the simplest model, perinatal mortality is independent of variation in target weight and determined solely by the magnitude of the perturbation of birth weight from the target. In this model, mortality risk is concentrated in the tails of the birth weight distribution. A difference between populations in their distributions of target weights will be associated with a corresponding shift in their curves of weight-specific risk, without any difference between the populations in overall risk. In this model, risk would be reduced by decreasing the variance of the distribution of perturbations. The model is discussed in the context of the so-called "paradoxes of low birth weight."

Haig D, Wharton R. Prader-Willi syndrome and the evolution of human childhood. Am J Hum Biol. 2003;15 :320-9.Abstract

The kinship theory of genomic imprinting predicts that imprinted genes have effects on asymmetric kin (relatives with different degrees of matrilineal and patrilineal relatedness). The most important interaction with such a relative is a child's interaction with its mother. Therefore, the study of imprinted genes and their phenotypic effects promises to provide insights into the evolution of mother-child relations. Prader-Willi syndrome (PWS) is caused by the absence of expression of genes at 15q11-q13 that are normally expressed only when paternally derived. The kinship theory predicts that children with PWS will fail to express behaviors that have increased mothers' costs of child-rearing. Our analysis focuses on aspects of the PWS phenotype that affect appetite and feeding. Immediately after birth, children with PWS have little appetite and are usually unable to suckle, but at some stage (usually within the first 2 years) they develop a voracious appetite and an obsession with food. We conjecture that this change in appetite reflects evolutionary forces associated with weaning. Immediately after birth, when a child is completely dependent on the breast, poor appetite reduced maternal costs. However, once a child was able to consume supplemental foods, maternal costs would have been reduced by children with increased, nonfastidious appetites.

Adams M, Andersen AM, Andersen PK, Haig D, Henriksen TB, Hertz-Picciotto I, Lie RT, Olsen J, Skjaerven R, Wilcox A. Sostrup statement on low birthweight. Int J Epidemiol. 2003;32 :884-5.
Wilkins JF, Haig D. What good is genomic imprinting: the function of parent-specific gene expression. Nat Rev Genet. 2003;4 :359-68.Abstract

Parent-specific gene expression (genomic imprinting) is an evolutionary puzzle because it forgoes an important advantage of diploidy--protection against the effects of deleterious recessive mutations. Three hypotheses claim to have found a countervailing selective advantage of parent-specific expression. Imprinting is proposed to have evolved because it enhances evolvability in a changing environment, protects females against the ravages of invasive trophoblast, or because natural selection acts differently on genes of maternal and paternal origin in interactions among kin. The last hypothesis has received the most extensive theoretical development and seems the best supported by the properties of known imprinted genes. However, the hypothesis is yet to provide a compelling explanation for many examples of imprinting.

Greenwood-Lee JM, Taylor PD, Haig D. The Inclusive fitness dynamics of genomic imprinting. Selection. 2002;2 :103-118.
Wilkins JF, Haig D. Parental modifiers, antisense transcripts and loss of imprinting. Proc Biol Sci. 2002;269 :1841-6.Abstract

The kinship theory of genomic imprinting has explained parent-specific gene expression as the outcome of an evolutionary conflict between the two alleles at a diploid locus of an offspring over how much to demand from parents. Previous models have predicted that maternally derived (madumnal) alleles will be silent at demand-enhancing loci, while paternally derived (padumnal) alleles will be silent at demand-suppressing loci, but these models have not considered the evolution of trans-acting modifiers that are expressed in parents and influence imprinted expression in offspring. We show that such modifiers will sometimes be selected to reactivate the silent padumnal allele at a demand-suppressing locus but will not be selected to reactivate the silent madumnal allele at a demand-enhancing locus. Therefore, imprinting of demand-suppressing loci is predicted to be less evolutionarily stable than imprinting of demand-enhancing loci.

Wilkins JF, Haig D. Genomic imprinting of two antagonistic loci. Proc Biol Sci. 2001;268 :1861-7.Abstract

We present a model that considers the coevolution of genomic imprinting at a growth factor locus and an antagonistic growth suppressor locus. With respect to the two loci considered independently, our model makes the familiar predictions that an imprinted growth factor locus will only be expressed from the paternally derived allele and an imprinted growth suppressor locus only from the maternally derived allele. In addition, our coevolutionary model allows us to make predictions regarding the sequence of evolutionary events necessary for generating such a system. We conclude that imprinting at the growth factor locus preceded the evolution of growth suppressor function at the second locus, which in turn preceded imprinting at that locus. We then discuss the consistency of these predictions with currently available comparative data on the insulin-like growth factor 2 insulin-like growth factor 2 receptor system of mammals.

Haig D. Of sex and gender. Nat Genet. 2000;25 :373.
Haig D. Genomic imprinting, sex-biased dispersal, and social behavior. Ann NY Acad Sci. 2000;907 :149-63.Abstract

Some genes carry a record of the sex of the gene's carrier in the previous generation that influences the gene's expression in this generation. This additional information can result in intragenomic conflicts between an individual's maternally and paternally derived alleles over behaviors that affect relatives with whom the individual has different degrees of maternal and paternal relatedness. Asymmetries of relatedness can arise because of sex-biased dispersal. For example, if females remain in their natal group and males disperse, female members of a group will all be matrilineal relatives, but may have unrelated fathers. Sex-linked inheritance creates an evolutionary bias in favor of social groups that trace descent through the homogametic sex. This bias has a positive and negative aspect. The positive aspect is increased relatedness among siblings of the homogametic sex. The negative aspect is the lack of sex-linked relatedness between parents and offspring of the heterogametic sex.