Thursday, May 28, 2009

Young human disease genes evolve slowly

imageGenes underlying human heritable diseases are not only important for medicine but are also of great interest for evolutionary biologists. This is because we know that such genes can be mutated to produce deleterious phenotypes and we can use them to study how function is acquired in evolution. In a paper just published in Genome Biology and Evolution and spearheaded by James Cai we show that disease genes evolve under strong functional constraint independently of their genomic age. This is quite different from other genes which show a marked trend of weaker constraint for genes that entered human genome more recently in evolutionary terms. Disease genes also tend to be expressed only in some tissues and appear to lack close duplicate copies. We argue that disease genes possess these features because they need to be sufficiently important such that mutations in them can be of noticeable functional significance. However, their expression and impact need to be limited to particular tissues because mutations in important genes expressed ubiquitously would generate embryonic lethals instead of disease. Finally, we believe that young human genes that evolve under strong constraint in humans might in general be enriched for genes that encode important primate or even human-specific functions. The study of such genes might be profitable and we intend to pursue this line of research in the future.

Monday, May 25, 2009

Unusual adaptation via TE-induced regulatory change in Juvenile hormone metabolism

imageWe recently demonstrated that transposable elements underlie much recent adaptation in Drosophila melanogaster (Gonzalez et al. 2008). In a paper just published by Molecular Biology and Evolution and led by Josefa Gonzalez we describe a follow-up detailed investigation of one such TE (called Bari-Jheh). Bari-Jheh is located inside a cluster of Juvenile hormone epoxyhydrolases (Jheh1, Jheh2, and Jheh3). We confirm that Bari-Jheh is the apparent cause of the adaptation and extend the study of its molecular effects to show that it leads to decreased expression of the neighboring Jheh genes (Jheh2 and Jheh3). Furthermore, we demonstrate that these molecular effects have predicted phenotypic effects on life history traits. The very curious part of this work is that Jheh genes appear very strongly conserved in evolution and do not show any signs of recurrent adaptation in Drosophila. The fact that in D. melanogaster we catch a recent adaptation in these genes might suggest that Bari-Jheh is either a very rare adaptive event and we were just lucky to catch it or that adaptation happens recurrently at the Jheh genes but leads to short-lived adaptive polymorphisms that are destined to be lost. This work further suggests that the focus on recurrent adaptation might obscure non-recurrent or ephemeral adaptation that might be important within species.

Sunday, May 3, 2009

Philip is awarded BioX and VPUE grants to study HIV transmission in Africa

imagePhilip Bulterys, an undergraduate in the lab, has received a UAR Major Grant and a Bio-X Undergraduate Research Award to pursue his study of the evolutionary dynamics of HIV-1 in the context of Mother-to-Child Transmission (MTCT). The project will involve comprehensive cloning and genotyping of HIV-1 found in plasma specimens (and other compartments) from infected mothers and their infants from prospective cohorts in Rwanda and Zambia. Together with collaborators at the Stanford School of Medicine, Philip will use molecular and epidemiological methods to characterize the relationship among viral diversity, strength of selection, and phylogenetics of HIV-1 and the risk of vertical HIV-1 transmission. Philip grew up in Rwanda and went to high school in Zambia (and has returned the last two summers to study malaria transmission dynamics in rural areas), so this project has personal meaning for him.