Evolutionary distances for protein-coding sequences: modeling site- specific residue frequencies

Estimation of evolutionary distances from coding sequences must take into account protein-level selection to avoid relative underestimation of longer evolutionary distances. Current modeling of selection via site-to-site rate heterogeneity generally neglects another aspect of selection, namely position-specific amino acid frequencies. These frequencies determine the maximum dissimilarity expected for highly diverged but functionally and structurally conserved sequences, and hence are crucial for estimating long distances. We introduce a codon- level model of coding sequence evolution in which position-specific amino acid frequencies are free parameters. In our implementation, these are estimated from an alignment using methods described previously. We use simulations to demonstrate the importance and feasibility of modeling such behavior; our model produces linear distance estimates over a wide range of distances, while several alternative models underestimate long distances relative to short distances. Site-to-site differences in rates, as well as synonymous/nonsynonymous and first/second/third-codon-position differences, arise as a natural consequence of the site-to-site differences in amino acid frequencies.      

The major locus for multifactorial nonsyndromic cleft lip maps to mouse Chromosome 11

Cleft lip with or without cleft palate, CL(P), a common human birth defect, has a genetically complex etiology. An animal model with a similarly complex genetic basis is established in the A/WySn mouse strain, in which 20% of newborn have CL(P). Using a newly created congenic strain, AEJ.A, and SSLP markers, we have mapped a major CL(P)-causing gene derived from the A/WySn strain. This locus, here named clf1 (cleft lip) maps to Chromosome (Chr) 11 to a region having linkage homology with human 17q21-24, supporting reports of association of human CL(P) with the retinoic acid receptor alpha (RARA) locus.     

Strategies for farmers and policy makers to control nitro-gen losses whilst maintaining crop production

The nitrogen (N) cycle is essentially 'leaky'. The losses of small amounts of nitrate to waters and of ammonia and nitrous oxide to the atmosphere are a part of the global biogeo-chemical N cycle. However, intensive agricultural production, industry and vehicle use have more than doubled the amount of 'reactive' N in the environment, resulting in eutrophication, ecosystem change and health concerns. Research has identified agricultural practices that cause large losses of N and, in some cases, developed solutions. This paper discusses the problems of maintaining productivity while reducing N losses, compares conventional with low input (integrated) and organic farming systems, and discusses wider options. It also looks at the need to integrate studies on N with other environmental impacts, set in the context of the whole farm system, to provide truly sustainable agricultural systems.     

The lidgap-Gates (lg Ga) mutation for open eyelids at birth maps to mouse Chromosome 13

Complex nonadditive interactions between specific alleles at multiple loci may underlie many so-called multifactorial threshold birth defects. The open-eyelids-at-birth defect in mice is a good model for these defects, and an understanding of its genetic complexity begins with mapping the participating loci. The open-eyelids defect can be part of a syndrome or can occur with no other obvious phenotypic effects. Of the latter nonsyndromic forms, the lidgap series includes four extant mutations that are considered to be alleles based on complementation tests. All show genetic complexity in segregation ratios. None has been mapped previously. On the basis of a strategy of mapping the mutation with the simplest inheritance pattern first, we generated an extensive exclusion map for lidgap-Gates, lg ^Ga , using morphological and protein polymorphisms. We then screened the non-excluded regions in a congenic strain, AEJ.LGG—lg ^Ga , for SSLP markers and located the differential chromosome segment containing the lg ^Ga locus in a region near the distal end of mouse Chromosome (Chr) 13. This linkage was confirmed and refined by typing SSLPs in 64 F₂ and 74 BC₁ progeny of a cross of LGG/Bc (lg ^Ga /lg ^Ga ) to SWV/Bc. The lg ^Ga mutation maps to a 1- to 2-cM region between D13Mit76 and D13Mit53. Integrin alpha 1 and integrin alpha 2, which map to the same general region, are possible candidate loci, based on their embryonic expression and cellular function. Evidence is also presented for a common unlinked recessive suppressor of the open eyelids trait caused by lg ^Ga . Received: 3 February 1995 / Accepted: 19 February 1996