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Germline mutation rates have been found to be higher in males than in females in many organisms, a likely consequence of cell division being more frequent in spermatogenesis than in oogenesis. If the majority of mutations are due to DNA replication error, the male-to-female mutation rate ratio (alpha(m)) is expected to be similar to the ratio of the number of germ line cell divisions in males and females (c), an assumption that can be tested with proper estimates of alpha(m) and c. Alpha(m) is usually estimated by comparing substitution rates in putatively neutral sequences on the sex chromosomes. However, substantial regional variation in substitution rates across chromosomes may bias estimates of alpha(m) based on the substitution rates of short sequences. To investigate regional substitution rate variation, we estimated sequence divergence in 16 gametologous introns located on the Z and W chromosomes of five bird species of the order Galliformes. Intron ends and potentially conserved blocks were excluded to reduce the effect of using sequences subject to negative selection. We found significant substitution rate variation within Z chromosome (G15 = 37.6, p = 0.0010) as well as within W chromosome introns (G15 = 44.0, p = 0.0001). This heterogeneity also affected the estimates of alpha(m), which varied significantly, from 1.53 to 3.51, among the introns (ANOVA: F(13,14) = 2.68, p = 0.04). Our results suggest the importance of using extensive data sets from several genomic regions to avoid the effects of regional mutation rate variation and to ensure accurate estimates of alpha(m).

We analyze recombination in C. jejuni using MLST data from isolates taken from wild birds, cattle, wild rabbits, and water in a 100-km2 study region in Cheshire, UK. We use a recent approximate likelihood method for inference, based on combining likelihood information from all pairs of segregating (polymorphic) sites in the data. We find substantial evidence for recombination, but only for recombination with short tract lengths, of around 225-750 bp. We estimate that the rate of recombination is of a similar magnitude to the rate of mutation.

The dogma of strict maternal inheritance of mitochondria is now being tested with population genetics methods on sequence data from many species. In this study we investigated whether recombination occurs in the mitochondria of the blue tit ( Parus caeruleus) by studying polymorphisms in the mitochondrial control region and in a recently identified (A)(n) microsatellite on the W chromosome. The female heterogamety of avian sex chromosomes allows a test of whether mitochondrial recombination affects genealogical inference by comparison of mitochondrial and W-linked sequence variation. There is no discrepancy between mitochondrial and W-linked genealogies in blue tits, consistent with no recombination. We also analyzed mitochondrial sequence variation in both blue tits and peregrine falcons ( Falco peregrinus) using a coalescent-based approach which accounts for recurrent mutation; in neither bird species did we find evidence of recombination. We conclude that it is unlikely that mitochondrial recombination has large effects on mitochondrial genetic variability in birds.

A DNA mutation in a protein coding gene which causes an amino acid change can be classified as "conservative" or "radical" depending on the magnitude of the physicochemical difference between the two amino acids: radical mutations involve larger changes than conservative mutations. Here, I examine two key issues in determining whether radical and conservative substitution rates are useful statistics in molecular evolution. The first issue is whether such rates can be estimated reliably, and for this purpose I demonstrate considerable improvements achieved by simple modifications to an existing method. The second issue is whether conservative and radical substitution rates can tell us something about selection on protein function. I address this problem by estimating positive and negative selection on conservative and radical mutations using polymorphism and divergence data from Drosophila. These analyses show that negative selection, but not positive selection, differs significantly between conservative and radical mutations. The power of conservative and radical substitution rates in testing the nearly neutral theory of molecular evolution is illustrated by the analysis of two mammalian datasets.

Murid rodents show much less variation in isochore base composition than do most other mammals, a difference which has been referred to as the murid shift. We have investigated the murid shift by asking (1) whether the murid shift is ongoing and (2) whether there is any evidence of selection or biased gene conversion affecting base composition in the present-day mouse genome. By estimating the ancestral base composition of protein-coding genes in murids we can confirm that the murid shift is ongoing. Tests using nongenic polymorphism data fail to reject the hypothesis that base composition is due to mutation bias alone. However, the patterns of compositional change suggested by the polymorphism and divergence data differ, suggesting the possibility of two murid shifts.

Natural selection favors certain synonymous codons which aid translation in Escherichia coli, yet codons not favored by translational selection persist. We use the frequency distributions of synonymous polymorphisms to test three hypotheses for the existence of translationally sub-optimal codons: (1) selection is a relatively weak force, so there is a balance between mutation, selection, and drift; (2) at some sites there is no selection on codon usage, so some synonymous sites are unaffected by translational selection; and (3) translationally sub-optimal codons are favored by alternative selection pressures at certain synonymous sites. We find that when all the data is considered, model 1 is supported and both models 2 and 3 are rejected as sole explanations for the existence of translationally sub-optimal codons. However, we find evidence in favor of both models 2 and 3 when the data is partitioned between groups of amino acids and between regions of the genes. Thus, all three mechanisms appear to contribute to the existence of translationally sub-optimal codons in E. coli.

In studies of molecular evolution, the assumption that protein evolution is reversible has often been made, but rarely tested. Here we use a large set of orthologous murid protein coding sequences to perform a simple test of reversibility, and find no evidence to reject the assumption of reversibility in protein evolution.