DirtyGenes: testing for significant changes in gene or bacterial population compositions from a small number of samples.

High throughput genomics technologies are applied widely to microbiomes in humans, animals, soil and water, to detect changes in bacterial communities or the genes they carry, between different environments or treatments. We describe a method to test the statistical significance of differences in bacterial population or gene composition, applicable to metagenomic or quantitative polymerase chain reaction data. Our method goes beyond previous published work in being universally most powerful, thus better able to detect statistically significant differences, and through being more reliable for smaller sample sizes. It can also be used for experimental design, to estimate how many samples to use in future experiments, again with the advantage of being universally most powerful. We present three example analyses in the area of antimicrobial resistance. The first is to published data on bacterial communities and antimicrobial resistance genes (ARGs) in the environment; we show that there are significant changes in both ARG and community composition. The second is to new data on seasonality in bacterial communities and ARGs in hooves from four sheep. While the observed differences are not significant, we show that a minimum group size of eight sheep would provide sufficient power to observe significance of similar changes in further experiments. The third is to published data on bacterial communities surrounding rice crops. This is a much larger data set and is used to verify the new method. Our method has broad uses for statistical testing and experimental design in research on changing microbiomes, including studies on antimicrobial resistance.

Menopause, evolution and changing cultures.

The menopause is an isolated event in a much wider process that was probably an evolutionary adaptation essential for survival in the Pliocene. As a reproductive strategy, it is largely vestigial in the 21st century, part of an era that has seen a doubling of the average human longevity compared with that of the past. This process commences as an accelerated decline in female fertility, usually from the fourth decade of life, culminating in a total cessation of reproductive capacity for those surviving. The 20th and 21st century sees a huge increase in the numbers surviving and the duration of that postreproductive life phase extending for decades. This extended period of what is essentially a hormone deficiency state is a recent phenomenon and by no means part of the natural history of the human individual. It is therefore not surprising to see a postmenopausal increase in the incidence of so many disorders above that expected by age alone. Recent reproductive patterns have seen increases in the birth rate and requests for fertility treatments among women in their late 30s and 40s. Many try for pregnancy but are unsuccessful. The genes that permit later reproduction and hence later menopause are therefore being preferentially selected. Slowly over generations we will expect to see the fertility of future 40 year olds increase and the age of menopause to extend much later into our, now, longer lives.