Lineage-Specific Variation in Intensity of Natural Selection in Mammals

Abstract

The molecular clock hypothesis states that protein-coding genes evolve at an approximately constant rate. However, this is only expected to be true as long as the function and the tertiary structure of the molecule remain unaltered. An important implication of this statement is that significant deviations in the rate of evolution of a gene with respect to the species clock are likely to reflect functional and/or structural alterations. Here, we present a method to identify such deviations and apply it to a data set of 2,929 high-quality coding sequence alignments corresponding to one-to-one orthologous genes from six mammalian species--human, macaque, mouse, rat, cow, and dog. Deviated branches are defined as those that present significant alterations in both the rate of nonsynonymous substitutions (dN) and the selective pressure (dN/dS). Strikingly, we find that as many as 24.5% of the genes show branch-specific deviations in dN and dN/dS, though this is a relatively well-conserved set of genes. Around half of these genes show branch-specific acceleration of evolutionary rates. Positive selection (PS) tests based on divergence data only identify 17.7% of the accelerated branches. Failure to identify PS in accelerated branches with an excess of radical amino acid replacements suggests that these tests are conservative. Interestingly, genes with accelerated branches are significantly enriched in neural proteins, indicating that this type of protein might play a more important role than previously thought in species diversification, although they are generally not detected by PS tests. We discuss in detail several examples of genes that show lineage-specific evolutionary rate acceleration and are involved in synaptic transmission, chemosensory perception, and ubiquitination.

Causes and evolutionary consequences of primordial germ-cell specification mode in metazoans

“…33) compared with other mammals concurs with the deterministicstochastic hypothesis (32). However, rapid sequence evolution in the mouse lineage is well known, and need not indicate a release of selection, but, rather, is likely an effect of their short generation time (34,35). As an example, an assessment of selection using dN/dS values (988 genes) has shown that mice (M. musculus) exhibit lower average values than other mammals such as pigs (Sus scrofa) and humans (Homo sapiens), suggesting greater purifying selection, and thus inconsistent with the extensive release of constraint predicted by the deterministic-stochastic hypothesis (ref.…”

“…34; see also ref. 35). Mice may be subjected to more restrained evolution than some other mammals simply due to their very large population sizes (34).…”

Computational Molecular Analysis of the Sequences of BMP15 Gene of Ruminants and Non-Ruminants

“…One of the key issues in biology, is understanding how natural selection drives gene functional diversification across different species and lineages [24]. The varying substitutions of amino acids within and across species might be as a result of separate divergence from their common ancestor.…”

Phylogenetic relationships of the Cobitoidea (Teleostei: Cypriniformes) inferred from mitochondrial and nuclear genes with analyses of gene evolution

“…For dN and dS, the former is considered to be related mainly to functional constraints (Kawahara and Imanishi, 2007), while the latter by purifying selection (Smith et al, 2008;Toll-Riera et al, 2011). For this reason, the nearly constant dN and significantly lower dS values of ND4 in the balitorid lineage suggests that it was mostly affected by relaxed purifying selection in this lineage.…”

“…Therefore, variation in evolutionary rates (e.g. dN/dS ratio), especially those between taxa sufficiently closely related (for example within mammals), is considered a strong indicator of anagenesis driven by selection pressure over time (Czelusniak et al, 1982;Kawahara and Imanishi, 2007;Lynch and Conery, 2000;Toll-Riera et al, 2011). This variation of possible factors is hypothesized to have contributed greatly to the function differentiation we observe today in the genes and diversification of organisms (Wang et al, 2009).…”