Thursday, March 11, 2010

Does Usain Bolt lack the ACTN3 R577X polymorphism?

...that's the question that pops into my mind after reading the title and abstract. I wonder if they genotyped the elite of the elite (Bolt, Powell) or just the "elite"? It looks like they did:
Forty-six of these international athletes had won medals at major international competition or held sprint world records.
Nevertheless, another negative finding on the association between the ACTN3 fast twitch muscle fiber, "sprint" genotype and sprint phenotypes. In fact, two of the elite-elite Jamaican sprinters were homozygous for the slow-twitch variant! They acknowledge that the power to detect a difference here is pretty low because of the very low frequency of the ACTN3 R5777X polymorphism in West Africans... so much for personalized prediction of sports ability, at least for now. I say just look at your big toe... does it extend out farther than your second toe? if so, you could probably be pretty fast.
Given these results, Usain probably does lack the ACTN3 polymorphism, but on the other hand, he could be the one of the two out of the 46 elite-elite sprinters who is homozygous for it.

P.S. - gotta love the senior author's name!

ACTN3 and ACE Genotypes in Elite Jamaican and US Sprinters
ABSTRACT The angiotensin-converting enzyme (ACE) and the [alpha]-actinin-3 (ACTN3) genes are two of the most studied "performance genes" and both have been associated with sprint/power phenotypes and elite performance. Purpose: To investigate the association between the ACE and the ACTN3 genotypes and sprint athlete status in elite Jamaican and US African American sprinters. Methods: The ACTN3 R577X and the ACE I/D and A22982G (rs4363) genotype distributions of elite Jamaican (J-A; N = 116) and US sprinters (US-A; N = 114) were compared with controls from the Jamaican (J-C; N = 311) and US African American (US-C; N = 191) populations. Frequency differences between groups were assessed by exact test. Results: For ACTN3, the XX genotype was found to be at very low frequency in both athlete and control cohorts (J-C = 2%, J-A = 3%, US-C = 4%, US-A = 2%). Athletes did not differ from controls in ACTN3 genotype distribution (J, P = 0.87; US, P = 0.58). Similarly, neither US nor Jamaican athletes differed from controls in genotype at ACE I/D (J, P = 0.44; US, P = 0.37). Jamaican athletes did not differ from controls for A22982G genotype (P = 0.28), although US sprinters did (P = 0.029), displaying an excess of heterozygotes relative to controls but no excess of GG homozygotes (US-C = 22%, US-A = 18%). Conclusions: Given that ACTN3 XX genotype is negatively associated with elite sprint athlete status, the underlying low frequency in these populations eliminates the possibility of replicating this association in Jamaican and US African American sprinters. The finding of no excess in ACE DD or GG genotypes in elite sprint athletes relative to controls suggests that ACE genotype is not a determinant of elite sprint athlete status.

More than one molecular way to adaptively change a phenotype

The authors report on their finding of different mutations in the same gene MC1R affecting different molecular pathways on the way to lighter pigmentation in lizards. There are several likely examples of molecularly divergent phenotypic convergence in humans, some of which may originate in the same gene: MC1R - skin color in Europeans and E. Asians, LCT - lactase persistence in Europe, Middle East, and E. Africa, and probably, adaptation to high altitude in E. Africa, Andes, and Himalayas.

The cool thing about this paper is that they use cell culture to find that even though the mutations are in the same gene, they result in lighter pigmentation through different molecular pathways.

Molecular and functional basis of phenotypic convergence in white lizards at White Sands
Erica Bree Rosenblum, Holger Römpler, Torsten Schöneberg, and Hopi E. Hoekstra
PNAS February 2, 2010 vol. 107 no. 5 2113-2117
Abstract: There are many striking examples of phenotypic convergence in nature, in some cases associated with changes in the same genes. But even mutations in the same gene may have different biochemical properties and thus different evolutionary consequences. Here we dissect the molecular mechanism of convergent evolution in three lizard species with blanched coloration on the gypsum dunes of White Sands, New Mexico. These White Sands forms have rapidly evolved cryptic coloration in the last few thousand years, presumably to avoid predation. We use cell-based assays to demonstrate that independent mutations in the same gene underlie the convergent blanched phenotypes in two of the three species. Although the same gene contributes to light phenotypes in these White Sands populations, the specific molecular mechanisms leading to reduced melanin production are different. In one case, mutations affect receptor signaling and in the other, the ability of the receptor to integrate into the melanocyte membrane. These functional differences have important ramifications at the organismal level. Derived alleles in the two species show opposite dominance patterns, which in turn affect their visibility to selection and the spatial distribution of alleles across habitats. Our results demonstrate that even when the same gene is responsible for phenotypic convergence, differences in molecular mechanism can have dramatic consequences on trait expression and ultimately the adaptive trajectory.

Tuesday, March 02, 2010

Chinese prefer darker-skinned pigs and MC1R tells part of the story

I'm not yet able to get full text access to this paper, but after looking into the related literature, I was suprised to see that there is quite a lot out there. Given that variation in MC1R was selected upon to lighten skin in Europeans, I was somewhat surprised to see the opposite happen in pigs.
Spaniards also like black pigs.
By the way, I'm not too fond of the term "artificial" in this type of context.

Artificial selection of the melanocortin receptor 1 gene in Chinese domestic pigs during domestication.
Li J, Yang H, Li JR, Li HP, Ning T, Pan XR, Shi P, Zhang YP
Heredity. 2010 Feb 24. [Epub ahead of print]
Abstract: Black coat colour is common in Chinese indigenous domestic pigs, but not among their wild ancestors, and it is thus presumed to be a 'domestication trait.' To determine whether artificial interference contributes to morphological diversification, we examined nucleotide variation from 157 Chinese domestic pigs and 40 wild boars in the melanocortin receptor 1 (MC1R) gene, which has a key role in the coat pigmentation of Sus scrofa. Compared with a pseudogene GPIP, our results showed that the joint effects of demography and selection have resulted in markedly low genetic diversity of MC1R in Chinese domestic pigs. Coalescent simulation and selection tests further suggest that the fixation of two non-synonymous substitutions associated with black colour is the result of artificial selection. In contrast, a much higher genetic diversity and only a single non-synonymous substitution were found among the wild boars, suggesting a strong functional constraint. Moreover, our conclusion is consistent with the preference for black colour in the ancient Chinese sacrificial culture. This case provides an interesting example of a molecular evaluation of artificial livestock selection and its associated cultural impact in ancient China.
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