Mutations within lncRNAs are effectively selected against in fruitfly but not in human

Background

Previous studies in Drosophila and mammals have revealed levels of long non-coding RNAs (lncRNAs) sequence conservation that are intermediate between neutrally evolving and protein-coding sequence. These analyses compared conservation between species that diverged up to 75 million years ago. However, analysis of sequence polymorphisms within a species'' population can provide an understanding of essentially contemporaneous selective constraints that are acting on lncRNAs and can quantify the deleterious effect of mutations occurring within these loci.

Results

We took advantage of polymorphisms derived from the genome sequences of 163 Drosophila melanogaster strains and 174 human individuals to calculate the distribution of fitness effects of single nucleotide polymorphisms occurring within intergenic lncRNAs and compared this to distributions for SNPs present within putatively neutral or protein-coding sequences. Our observations show that in D.melanogaster there is a significant excess of rare frequency variants within intergenic lncRNAs relative to neutrally evolving sequences, whereas selection on human intergenic lncRNAs appears to be effectively neutral. Approximately 30% of mutations within these fruitfly lncRNAs are estimated as being weakly deleterious.

Conclusions

These contrasting results can be attributed to the large difference in effective population sizes between the two species. Our results suggest that while the sequences of lncRNAs will be well conserved across insect species, such loci in mammals will accumulate greater proportions of deleterious changes through genetic drift.     

A microsatellite-based analysis for the detection of selection on BTA1 and BTA20 in northern Eurasian cattle (Bos taurus) populations

Background

Microsatellites surrounding functionally important candidate genes or quantitative trait loci have received attention as proxy measures of polymorphism level at the candidate loci themselves. In cattle, selection for economically important traits is a long-term strategy and it has been reported that microsatellites are linked to these important loci.

Methods

We have investigated the variation of seven microsatellites on BTA1 (Bos taurus autosome 1) and 16 on BTA20, using bovine populations of typical production types and horn status in northern Eurasia. Genetic variability of these loci and linkage disequilibrium among these loci were compared with those of 28 microsatellites on other bovine chromosomes. Four different tests were applied to detect molecular signatures of selection.

Results

No marked difference in locus variability was found between microsatellites on BTA1, BTA20 and the other chromosomes in terms of different diversity indices. Average D'' values of pairwise syntenic markers (0.32 and 0.28 across BTA 1 and BTA20 respectively) were significantly (P < 0.05) higher than for non-syntenic markers (0.15). The Ewens-Watterson test, the Beaumont and Nichol''s modified frequentist test and the Bayesian F_ST-test indicated elevated or decreased genetic differentiation, at SOD1 and AGLA17 markers respectively, deviating significantly (P < 0.05) from neutral expectations. Furthermore, lnRV, lnRH and lnRθ'' statistics were used for the pairwise population comparison tests and were significantly less variable in one population relative to the other, providing additional evidence of selection signatures for two of the 51 loci. Moreover, the three Finnish native populations showed evidence of subpopulation divergence at SOD1 and AGLA17. Our data also indicate significant intergenic linkage disequilibrium around the candidate loci and suggest that hitchhiking selection has played a role in shaping the pattern of observed linkage disequilibrium.

Conclusion

Hitchhiking due to tight linkage with alleles at candidate genes, e.g. the POLL gene, is a possible explanation for this pattern. The potential impact of selective breeding by man on cattle populations is discussed in the context of selection effects. Our results also suggest that a practical approach to detect loci under selection is to simultaneously apply multiple neutrality tests based on different assumptions and estimations.     

The influences of PRG-1 on the expression of small RNAs and mRNAs

Background

In metazoans, Piwi-related Argonaute proteins play important roles in maintaining germline integrity and fertility and have been linked to a class of germline-enriched small RNAs termed piRNAs. Caenorhabditis elegans encodes two Piwi family proteins called PRG-1 and PRG-2, and PRG-1 interacts with the C. elegans piRNAs (21U-RNAs). Previous studies found that mutation of prg-1 causes a marked reduction in the expression of 21U-RNAs, temperature-sensitive defects in fertility and other phenotypic defects.

Results

In this study, we wanted to systematically demonstrate the function of PRG-1 in the regulation of small RNAs and their targets. By analyzing small RNAs and mRNAs with and without a mutation in prg-1 during C. elegans development, we demonstrated that (1) mutation of prg-1 leads to a decrease in the expression of 21U-RNAs, and causes 35 ~ 40% of miRNAs to be down-regulated; (2) in C. elegans, approximately 3% (6% in L4) of protein-coding genes are differentially expressed after mutating prg-1, and 60 ~ 70% of these substantially altered protein-coding genes are up-regulated; (3) the target genes of the down-regulated miRNAs and the candidate target genes of the down-regulated 21U-RNAs are enriched in the up-regulated protein-coding genes; and (4) PRG-1 regulates protein-coding genes by down-regulating small RNAs (miRNAs and 21U-RNAs) that target genes that participate in the development of C. elegans.

Conclusions

In prg-1-mutated C. elegans, the expression of miRNAs and 21U-RNAs was reduced, and the protein-coding targets, which were associated with the development of C. elegans, were up-regulated. This may be the mechanism underlying PRG-1 function.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-321) contains supplementary material, which is available to authorized users.     

Allometry of Sexual Size Dimorphism in Domestic Dog

Background

The tendency for male-larger sexual size dimorphism (SSD) to scale with body size – a pattern termed Rensch''s rule – has been empirically supported in many animal lineages. Nevertheless, its theoretical elucidation is a subject of debate. Here, we exploited the extreme morphological variability of domestic dog (Canis familiaris) to gain insights into evolutionary causes of this rule.

Methodology/Principal Findings

We studied SSD and its allometry among 74 breeds ranging in height from less than 19 cm in Chihuahua to about 84 cm in Irish wolfhound. In total, the dataset included 6,221 individuals. We demonstrate that most dog breeds are male-larger, and SSD in large breeds is comparable to SSD of their wolf ancestor. Among breeds, SSD becomes smaller with decreasing body size. The smallest breeds are nearly monomorphic.

Conclusions/Significance

SSD among dog breeds follows the pattern consistent with Rensch''s rule. The variability of body size and corresponding changes in SSD among breeds of a domestic animal shaped by artificial selection can help to better understand processes leading to emergence of Rensch''s rule.