A first trial of retrospective collaboration for positional cloning in complex inheritance: Assay of the cytokine region on chromosome 5 by the Consortium on Asthma Genetics (COAG)

The central problem of complex inheritance is to map oligogenes for disease susceptibility, integrating linkage and association over samples that differ in several ways. Combination of evidence over multiple samples with 1,037 families supports loci contributing to asthma susceptibility in the cytokine region on 5q [maximum logarithm of odds (lod) = 2.61 near IL-4], but no evidence for atopy. The principal problems with retrospective collaboration on linkage appear to have been solved, providing far more information than a single study. A multipoint lod table evaluated at commonly agreed reference loci is required for both collaboration and metaanalysis, but variations in ascertainment, pedigree structure, phenotype definition, and marker selection are tolerated. These methods are invariant with statistical methods that increase the power of lods and are applicable to all diseases, motivating collaboration rather than competition. In contrast to linkage, positional cloning by allelic association has yet to be extended to multiple samples, a prerequisite for efficient combination with linkage and the greatest current challenge to genetic epidemiology.

Does recombination improve selection on codon usage? Lessons from nematode and fly complete genomes

Understanding the factors responsible for variations in mutation patterns and selection efficacy along chromosomes is a prerequisite for deciphering genome sequences. Population genetics models predict a positive correlation between the efficacy of selection at a given locus and the local rate of recombination because of Hill–Robertson effects. Codon usage is considered one of the most striking examples that support this prediction at the molecular level. In a wide range of species including Caenorhabditis elegans and Drosophila melanogaster, codon usage is essentially shaped by selection acting for translational efficiency. Codon usage bias correlates positively with recombination rate in Drosophila, apparently supporting the hypothesis that selection on codon usage is improved by recombination. Here we present an exhaustive analysis of codon usage in C. elegans and D. melanogaster complete genomes. We show that in both genomes there is a positive correlation between recombination rate and the frequency of optimal codons. However, we demonstrate that in both species, this effect is due to a mutational bias toward G and C bases in regions of high recombination rate, possibly as a direct consequence of the recombination process. The correlation between codon usage bias and recombination rate in these species appears to be essentially determined by recombination-dependent mutational patterns, rather than selective effects. This result highlights that it is necessary to take into account the mutagenic effect of recombination to understand the evolutionary role and impact of recombination.

Genetics and the origin of bird species

External (environmental) factors affecting the speciation of birds are better known than the internal (genetic) factors. The opposite is true for several groups of invertebrates, Drosophila being the outstanding example. Ideas about the genetics of speciation in general trace back to Dobzhansky who worked with Drosophila. These ideas are an insufficient guide for reconstructing speciation in birds for two main reasons. First, speciation in birds proceeds with the evolution of behavioral barriers to interbreeding; postmating isolation usually evolves much later, perhaps after gene exchange has all but ceased. As a consequence of the slow evolution of postmating isolating factors the scope for reinforcement of premating isolation is small, whereas the opportunity for introgressive hybridization to influence the evolution of diverging species is large. Second, premating isolation may arise from nongenetic, cultural causes; isolation may be affected partly by song, a trait that is culturally inherited through an imprinting-like process in many, but not all, groups of birds. Thus the genetic basis to the origin of bird species is to be sought in the inheritance of adult traits that are subject to natural and sexual selection. Some of the factors involved in premating isolation (plumage, morphology, and behavior) are under single-gene control, most are under polygenic control. The genetic basis of the origin of postmating isolating factors affecting the early development of embryos (viability) and reproductive physiology (sterility) is almost completely unknown. Bird speciation is facilitated by small population size, involves few genetic changes, and occurs relatively rapidly.