Detecting Site-Specific Physicochemical Selective Pressures: Applications to the Class I HLA of the Human Major Histocompatibility Complex and the SRK of the Plant Sporophytic Self-Incompatibility System

Abstract

Models of codon substitution are developed that incorporate physicochemical properties of amino acids. When amino acid sites are inferred to be under positive selection, these models suggest the nature and extent of the physicochemical properties selected for. This is accomplished by first partitioning the codons based on some property of the amino acids they code for, and then using this partition to parametrize the rates of property-conserving and property-altering base substitutions at the codon level by means of finite mixtures of Markov models that also account for codon and transition:transversion biases. Here, we apply this method to two positively-selected receptors involved in ligand-recognition; the class-I alleles of the human Major Histocompatibility Complex (MHC) of known structure and the S-locus Receptor Kinase (SRK) of the sporophytic self-incompatibility system (SSI) in cruciferous plants (Brassicaceae), whose structure is unknown. Through likelihood ratio tests we demonstrate that the positively selected MHC and SRK proteins are under physico-

Molecular Characterization of Lal2, an SRK-Like Gene Linked to the S-Locus in the Wild Mustard Leavenworthia alabamica

“…This approach calculates posterior probabilities of positive selection (as determined from the ratio of nonsynonymous substitution per nonsynonymous site to synonymous substitution per synonymous site) for individual codons, using an empirical Bayesian approach. The maximum-likelihood tree topology for the Lal2 sequences was first obtained using the branch-andbound algorithm as implemented in PAUP for the Kimura twoparameter model (Kimura 1980;Swofford 2002), and the selection analysis was conducted using the CODEML program of Yang (1997), as decribed by Sainudiin et al (2005). The number of Lal2 sequences available to us for analysis (10 sequences) was much smaller than those analyzed by Sainudiin et al (2005), who used the same method to detect specific classes of positive selection (e.g., polar-or volume-changing amino acid substitutions) in SRK sequences of Brassica and Arabidopsis.…”

“…The Lal2 sequences were examined for evidence of balancing selection and, in particular, evidence of ''hypervariable'' regions that have been proposed to harbor sites controlling S-allele recognition (Sainudiin et al 2005). Figure 5 shows a sliding-window analysis of nucleotide variability calculated for the alignment of long Lal2 sequences with alleles of SRK sampled in Arabidopsis and class I alleles in Brassica.…”

“…The maximum-likelihood tree topology for the Lal2 sequences was first obtained using the branch-andbound algorithm as implemented in PAUP for the Kimura twoparameter model (Kimura 1980;Swofford 2002), and the selection analysis was conducted using the CODEML program of Yang (1997), as decribed by Sainudiin et al (2005). The number of Lal2 sequences available to us for analysis (10 sequences) was much smaller than those analyzed by Sainudiin et al (2005), who used the same method to detect specific classes of positive selection (e.g., polar-or volume-changing amino acid substitutions) in SRK sequences of Brassica and Arabidopsis. Hence, our focus was on evidence of any type of positively selected amino acid substitution, regardless of the particular type of property-changing characteristic.…”

Structural modules for receptor dimerization in the S -locus receptor kinase extracellular domain

“…8). The variability in this ''linker'' region among SRK variants (19,20) suggests that the exact spacing of LLD1 and LLD2 is not critical for SRK function.…”

“…The eSRK PAN APPLE domain is contained within the so-called C-terminal variable region (VR) (19,20), which is one of four regions that exhibit extensive variability among SRK alleles (SI Fig. 8).…”