July 17, 2014

More selection on the X than in autosomes in humans

Mol Biol Evol (2014) doi: 10.1093/molbev/msu166

Evidence for Increased Levels of Positive and Negative Selection on the X Chromosome versus Autosomes in Humans

Krishna R. Veeramah et al.

Partially recessive variants under positive selection are expected to go to fixation more quickly on the X chromosome as a result of hemizygosity, an effect known as faster-X. Conversely, purifying selection is expected to reduce substitution rates more effectively on the X chromosome. Previous work in humans contrasted divergence on the autosomes and X chromosome, with results tending to support the faster-X effect. However, no study has yet incorporated both divergence and polymorphism to quantify the effects of both purifying and positive selection, which are opposing forces with respect to divergence. In this study, we develop a framework that integrates previously developed theory addressing differential rates of X and autosomal evolution with methods that jointly estimate the level of purifying and positive selection via modeling of the distribution of fitness effects (DFE). We then utilize this framework to estimate the proportion of nonsynonymous substitutions fixed by positive selection (α) using exome sequence data from a West African population. We find that varying the female to male breeding ratio (β) has minimal impact on the DFE for the X chromosome, especially when compared with the effect of varying the dominance coefficient of deleterious alleles (h). Estimates of α range from 46% to 51% and from 4% to 24% for the X chromosome and autosomes, respectively. While dependent on h, the magnitude of the difference between α values estimated for these two systems is highly statistically significant over a range of biologically realistic parameter values, suggesting faster-X has been operating in humans.



CarolAST said...

On a related note, this study came out not log ago, but no one seems to have commented on it.

Mol Biol Evol. 2014 May 8. [Epub ahead of print]
Inter- and intra-species phylogenetic analyses reveal extensive X-Y gene conversion in the evolution of gametologous sequences of human sex chromosomes.
Trombetta B1, Sellitto D, Scozzari R, Cruciani F.

It has long been believed that the Male Specific region of the human Y chromosome (MSY) is genetically independent from the X chromosome. This idea has been recently dismissed due to the discovery that X-Y gametologous gene conversion may occur. However, the pervasiveness of this molecular process in the evolution of sex chromosomes has yet to be exhaustively analyzed. In this study, we explored how pervasive X-Y gene conversion has been during the evolution of the youngest stratum of the human sex chromosomes. By comparing about 0.5 Mb of human-chimpanzee gametologous sequences, we identified 19 regions in which extensive gene conversion has occurred. From our analysis, two major features of these emerged: 1) several of them are evolutionarily conserved between the two species and 2) almost all of the nineteen hotspots overlap with regions where X-Y crossing-over has been previously reported to be involved in sex reversal. Furthermore, in order to explore the dynamics of X-Y gametologous conversion in recent human evolution, we re-sequenced these nineteen hotspots in 68 widely divergent Y haplogroups, and used publicly available SNP data for the X chromosome. We found that at least ten hotspots are still active in humans. Hence, the results of the interspecific analysis are consistent with the hypothesis of widespread reticulate evolution within gametologous sequences in the differentiation of hominini sex chromosomes. In turn, intraspecific analysis demonstrates that X-Y gene conversion may modulate human sex-chromosome-sequence evolution to a greater extent than previously thought.


Long story short: E1b1a1a [African] and everything from H1 to T [Eurasian excluding C thru G] have red V332
CER7 [C-site-Enriched Regions]

LivoniaG said...

“However, no study has yet incorporated both divergence and polymorphism to quantify the effects of both purifying and positive selection, which are opposing forces with respect to divergence.”

It would a good deal more realistic and useful if this kind of hardened modeling got back to the real world and actual evolutionary mechanics.

If you make fitness a constant, then you will never model, much less observe, the actual processes going on.

Environmental change is constantly varying the fitness values of all sorts of traits. So, over time, the same trait can bounce back and forth between positive, neutral and negative selection. (“Purifying” is a such a silly way to describe negative selection.)

Despite what the authors say, negative (“purifying”) selection may in fact increase divergence and diversity. You can see this in the operation of evolutionary algorithms, where negative selection acts as a kind of alternating pump, decreasing and then increasing diversity over time.

Key to understanding this more complex process is that variance in the environment and fitness is always a part of the analysis.

And it is also important, of course, to understand the real world response to changes in the environment may not be genetic change. More effective and immediate is human engineered solutions. (E.g., an answer to suddenly highly ”deleterious” ultraviolet sunlight upon the skin of a affected population will not be genetic change but might simply using more sun screen lotion. Much quicker. Much more effective.)

When human engineering (ie, culture) intervenes, all bets are off on what what is positive or deleterious. And that should inform any static selection model.

eurologist said...


Thanks for that link. I have previously pointed out papers on the preponderance of recombination in so-called non-recombining regions of the y-chromosome - this goes a bit further.