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David Haig

Publications and source records attributed to David Haig.

24 records · Page 2Linked to original sources
PubMed2003

What good is genomic imprinting: the function of parent-specific gene expression.

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.

Animals↗
PubMed2003

Meditations on birth weight: is it better to reduce the variance or increase the mean?

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."

Birth Weight↗
PubMed2002

Parental modifiers, antisense transcripts and loss of imprinting.

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.

Alleles↗
PubMed2002

Orf virus-encoded interleukin-10 stimulates the proliferation of murine mast cells and inhibits cytokine synthesis in murine peritoneal macrophages.

Orf virus (ORFV) is the type species of the parapoxvirus genus and produces cutaneous pustular lesions in sheep, goats and humans. The genome encodes a polypeptide with remarkable homology to interleukin-10 (IL-10), particularly ovine IL-10, and also to IL-10-like proteins encoded by Epstein-Barr virus (EBV) and equine herpesvirus. IL-10 is a pleiotropic cytokine that can exert either immunostimulatory or immunosuppressive effects on many cell types. We have expressed and purified C-terminal FLAG and His(6)-tagged versions of ORFV-IL-10 and shown that ORFV-IL-10 costimulates murine mast cells (MC/9) and inhibits tumour necrosis factor-alpha synthesis in activated mouse peritoneal macrophages. Our results demonstrate that although ORFV-IL-10 is structurally similar to EBV-IL-10 it has evolved a different spectrum of activities. EBV-IL-10 does not stimulate the proliferation of thymocytes or mast cells whereas ORFV-IL-10 has both of these activities. Recent studies show that the critical difference in molecular structure of human IL-10 and EBV-IL-10, which may be the basis of their functional differences, is linked to a single amino acid substitution. Consistent with the activity spectrum reported here for ORFV-IL-10, the viral gene encodes the critical amino acid seen in human IL-10. Although the ORFV-IL-10 gene has clearly undergone significant evolutionary change at the nucleotide level compared with ovine IL-10, it has largely retained the polypeptide structure and functional characteristics of its ovine counterpart, suggesting that mutations of the gene to a potentially more potent immunosuppressive form may compromise the co-existence of host and virus.

Amino Acid Sequence↗
PubMedDate not supplied

Prader-Willi syndrome and the evolution of human childhood.

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.

Appetite↗