High functional diversity of Mycobacterium tuberculosis

Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. In a paper just published in PloS Biology Ruth Hershberg, Mikhail Lipatov, Dmitri A. Petrov, Peter M. Small, Marcus W. Feldman, Sebastien Gagneux and colleagues surveyed sequence diversity within a global collection of strains belonging to MTBC. They demonstrated that the members of MTBC affecting humans are more genetically diverse than was generally assumed, and that this diversity can be linked to human demographic and migratory events. Furthermore, they showed that MTBC bacteria are under extremely reduced purifying selection and that as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. These findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis, could contribute to the emergence and spread of drug-resistant tuberculosis. This article was featured as a Science Journal Editor�s Choice.

New and improved D. melanogaster recombination rate calculator is available

Anna-sophie Fiston-Lavier further improved the Recombination Rate Calculator. The previously implemented procedure consistently overestimated recombination rate at telomeres. We now define regions of essentially no recombination near telomeres and set recombination rate there at zero. The exact procedure is described in http://petrov.stanford.edu/cgi-bin/recombination-rates_updateR5.pl. We are grateful to Peter Andolfatto for pointing this problem out.

Inferring selection strength under complex demographic scenarios

The strength of natural selection against transposable elements (TEs) can be inferred from the frequencies of a sample of TEs. However, complicated demographic histories could lead to a substantial distortion of the TE frequency distribution compared to that expected for a panmictic, constant-sized population. In a paper just published by MBE Josefa Gonzalez, Mike Macpherson, Philip Messer, and Dmitri develop a flexible maximum likelihood methodology that explicitly accounts both for demographic history and for the ascertainment biases of identifying TEs. We apply this method to the newly generated frequency data of the BS family of non-LTR retrotransposons in D. melanogaster in concert with two recent models of the demographic history of the species to infer the intensity of selection against this family. We find the estimate to differ substantially from our own prior estimates made under the assumptions of panmixis. These findings highlight the importance of accounting for demographic history and bear on study design for the inference of selection coefficients generally.

Selection on codon bias

In a wide variety of organisms, synonymous codons are used with different frequencies, in a phenomenon known as codon bias. In an article just published in the Annual Review of Genetics, Ruth and Dmitri discuss the current understanding of the ways in which natural selection participates in the creation and maintenance of codon bias. We also raise several open questions: (i ) Is natural selection on codon bias always weak as suggested by a number of studies or is it weak only at equlibrium? (ii ) What determines the identity of the selectively optimal codons? (iii ) How do shifts in the identity of optimal codons take place? (iv) What is the exact nature of selection on codon bias?

High rate of transposable element-induced adaptation in Drosophila

PloS Biology today published a paper by Gonzalez, J., Lenkov, K., Lipatov, M., Macpherson, J.M., and D.A. Petrov on the high rate of recent transposable element-induced adaptations in Drosophila melanogaster. In this work, we describe the first comprehensive genome-wide screen for recent adaptive TE insertions in D. melanogaster. Using several independent criteria, we identified a set of 13 adaptive TEs and estimate that 25-50 TEs have played adaptive roles since the migration of D. melanogaster out of Africa. We show that most of these adaptive TEs are likely to be involved in regulatory changes and appear to be involved in adaptation to the temperate climate. We argue that most identified adaptive TEs are destined to be lost from the D. melanogaster population but that they do contribute significantly to local adaptation in this species.

High redundancy and little new functionality among duplicated genes in yeast

PLoS Genetics published today a paper by Dean, J., Davis, J.C., Davis, R.W., and D.A. Petrov on the pervasive redundancy and apparent lack of new functionality among duplicated genes in yeast. We built a large number of yeast strains carrying single and double gene deletions of duplicated genes and measured their growth rates in rich medium. Using these data, we determined that many duplicated genes are functionally redundant to a substantial degree. We also demonstrated that the fitness effects of double deletions of duplicate genes are indistinguishable from our best estimate of the fitness effects of deletions of their ancestral singleton genes. We therefore argued that many duplicate genes do not gain substantial new functionality at least in the rich medium. Our results suggest that subfunctionalization does not generally proceed to completion, even after very long periods of time, and that neofunctionalization is either rare or of little consequence, at least under some growth conditions. This work was a collaboration between the Petrov and Davis labs.

Fake partial selective sweeps

A beneficial mutation that has nearly but not yet fixed in a population produces a characteristic haplotype configuration, called a partial selective sweep. Whether nonadaptive processes might generate similar haplotype configurations has not been extensively explored. In a paper by Macpherson, J.M., Gonzalez, J., Witten, D., Davis, J.C., Rosenberg, N., Hirsh, A.E., and D. A. Petrov that was just published by Molecular Biology and Evolution, we demonstrate that a number of non-adaptive processes can indeed lead to haplotype configurations that resemble partial selective sweeps. We show that recent bottlenecks are particularly powerful in this regard. This work emphasizes the importance of knowing demographic history in interpreting population genetic data.