Adaptive evolution in mitochondria & lifespan genes

In evolutionary biology, much is made of the tiny sequence difference between humans and chimpanzees. Our two species differ, on average, by only 1 out of 100 nucleotides — and in these small differences much lie the whole explanation for the phenotypic differences between H. sapiens and P. troglodytes. Fair enough, though I think the “1 out of 100” statistic is a little bit misleading: the differences are not evenly distributed throughout the genome; besides, any modern biologist worth their pipet tips knows that small changes in regulatory regions can have dramatic, disproportionate effects on phenotype.

By this logic, sequence divergence between humans and chimps should also help explain the (small) difference in our two species’ lifespans, and the (somewhat larger) differences in how we acquire and manifest age-related disease. To the extent that these phenotypic differences are guided by evolutionary pressures (e.g., grandmother selection), we should see evidence of adaptive change at the sequence level.

Uddin et al. looked for such evidence (cleverly, they searched not only in comparisons between humans and chimps, but more comprehensively throughout the mammalian lineage). They find that there is indeed evidence of adaptive evolution in aging-related pathways, but that the history of these changes is much more ancient than the divergence between the great apes:

Distinct genomic signatures of adaptation in pre- and postnatal environments during human evolution

The human genome evolution project seeks to reveal the genetic underpinnings of key phenotypic features that are distinctive of humans, such as a greatly enlarged cerebral cortex, slow development, and long life spans. This project has focused predominantly on genotypic changes during the 6-million-year descent from the last common ancestor (LCA) of humans and chimpanzees. Here, we argue that adaptive genotypic changes during earlier periods of evolutionary history also helped shape the distinctive human phenotype. Using comparative genome sequence data from 10 vertebrate species, we find a signature of human ancestry-specific adaptive evolution in 1,240 genes during their descent from the LCA with rodents. We also find that the signature of adaptive evolution is significantly different for highly expressed genes in human fetal and adult-stage tissues. Functional annotation clustering shows that on the ape stem lineage, an especially evident adaptively evolved biological pathway contains genes that function in mitochondria, are crucially involved in aerobic energy production, and are highly expressed in two energy-demanding tissues, heart and brain. Also, on this ape stem lineage, there was adaptive evolution among genes associated with human autoimmune and aging-related diseases. During more recent human descent, the adaptively evolving, highly expressed genes in fetal brain are involved in mediating neuronal connectivity. Comparing adaptively evolving genes from pre- and postnatal-stage tissues suggests that different selective pressures act on the development vs. the maintenance of the human phenotype.

That they observe prominent changes in brain genes is perhaps unsurprising, since we flatter ourselves with the idea that our brains are very different from those of our closest extant relatives. From a biogerontologist’s perspective, however, the brain is not only the seat of major behavioral and cognitive differences between species, but also the site of a great deal of aging-related action (developmental, neurodegenerative, and “normal” aging).