John C. Avise--recipient of 2006 Molecular Ecology prize.
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Awards and Prizes↗
Biomedical subjects
Francisco J Ayala
Publications and source records attributed to Francisco J Ayala.
Positive and negative selection in the beta-esterase gene cluster of the Drosophila melanogaster subgroup.
We examine the pattern of molecular evolution of the beta-esterase gene cluster, including the Est-6 and psiEst-6 genes, in eight species of the Drosophila melanogaster subgroup. Using maximum likelihood estimates of nonsynonymous/synonymous rate ratios, we show that the majority of Est-6 sites evolves under strong (48% of sites) or moderate (50% of sites) negative selection and a minority of sites (1.5%) is under significant positive selection. Est-6 sites likely to be under positive selection are associated with increased intraspecific variability. One positively selected site is responsible for the EST-6 F/S allozyme polymorphism; the same site is responsible for the EST-6 functional divergence between species of the melanogaster subgroup. For psiEst-6 83.7% sites evolve under negative selection, 16% sites evolve neutrally, and 0.3% sites are under positive selection. The positively selected sites of psiEst-6 are located at the beginning and at the end of the gene, where there is reduced divergence between D. melanogaster and D. simulans; these regions of psiEst-6 could be involved in regulation or some other function. Branch-site-specific analysis shows that the evolution of the melanogaster subgroup underwent episodic positive selection. Collating the present data with previous results for the beta-esterase genes, we propose that positive and negative selection are involved in a complex relationship that may be typical of the divergence of duplicate genes as one or both duplicates evolve a new function.
Animals↗
Clonal population structure and genetic diversity of Candida albicans in AIDS patients from Abidjan (Côte d'Ivoire).
We have investigated the genotype at 14 enzyme-encoding loci in 275 isolates of the pathogenic yeast Candida albicans sampled from 42 HIV-positive patients (all but one with AIDS) from Abidjan (Côte d'Ivoire). We separately analyzed the following variables: patient, residence, age, gender, T cell count, hospitalization (yes or no), drug treatment, date of sampling, multilocus genotype, and serotype. The most important factors contributing to the genetic variability of C. albicans are individual patient and gender. Our data manifest that the population size of the parasite is relatively small within each patient, although larger in women than in men, and that, at least for the patients involved in the study, the transmission rate of C. albicans between human adults is very low. Most important is the inference that the prevailing mode of reproduction of C. albicans in natural populations is clonal, so that sexual reproduction is extremely rare, if it occurs at all.
AIDS-Related Opportunistic Infections↗
Origins and evolution of spliceosomal introns.
Research into the origins of introns is at a critical juncture in the resolution of theories on the evolution of early life (which came first, RNA or DNA?), the identity of LUCA (the last universal common ancestor, was it prokaryotic- or eukaryotic-like?), and the significance of noncoding nucleotide variation. One early notion was that introns would have evolved as a component of an efficient mechanism for the origin of genes. But alternative theories emerged as well. From the debate between the "introns-early" and "introns-late" theories came the proposal that introns arose before the origin of genetically encoded proteins and DNA, and the more recent "introns-first" theory, which postulates the presence of introns at that early evolutionary stage from a reconstruction of the "RNA world." Here we review seminal and recent ideas about intron origins. Recent discoveries about the patterns and causes of intron evolution make this one of the most hotly debated and exciting topics in molecular evolutionary biology today.
Animals↗
Models of spliceosomal intron proliferation in the face of widespread ectopic expression.
It is now certain that today living organisms can acquire new spliceosomal introns in their genes. The proposed sources of spliceosomal introns are exons, transposons, and other introns, including spliceosomal and group II self-splicing introns. Spliceosomal introns are thought to be the most likely source, because the inserted sequence would immediately be endowed with the essential set of intron recognition sequences, thereby preventing the deleterious effects associated with incorrect splicing. The most obvious spliceosomal intron duplication pathways involve an RNA transcript intermediate step. Therefore, for a spliceosomal intron to be originated by duplication, either the source gene from which the novel intron is derived, or that gene and the recipient gene, which contains the novel intron, would need to be expressed in the germ line. Intron proliferation surveys indicate that putative intron duplicate-containing genes do not always match detectable expression in the germ line, which casts doubt on the generality of the duplication model. However, judging mechanisms of intron gain (or loss) from present-day gene expression profiles could be erroneous, if expression patterns were different at the time the introns arose. In fact, this may likely be so in most cases. Ectopic expression, i.e., the expression of genes at times and locations where the target gene is not known to have a function, is a much more common phenomenon than previously realized. We conclude with a speculation on a possible interplay between spliceosomal introns and ectopic expression at the origin of multicellularity.
Animals↗
Plasmodium vivax: recent world expansion and genetic identity to Plasmodium simium.
Plasmodium vivax causes the most geographically widespread human malaria, accounting annually for 70-80 million clinical cases throughout the tropical and subtropical regions of the world's continents. We have analyzed the DNA sequences of the Csp (circumsporozoite protein) gene in 24 geographically representative strains of P. vivax and 2 of P. simium, which parasitizes several species of New World monkeys. The Csp sequences are of two types, VK210 and VK247, which differ by three diagnostic amino acid replacements, one in each of the 5' and 3' terminal regions [5' nonrepeat (NR) and 3' NR] of the gene and in an insertion sequence that precedes the 3' NR region. The central region of the gene consists of approximately 38 repetitive "motifs," which are alternatively four and five amino acids long, which also are diagnostically different between the VK210 and VK247 types. There are very few synonymous substitutions within and between the two types of strains, which we hypothesize reflects that the worldwide spread of P. vivax is very recent. The two P. simium Csp sequences belong one to each of the two VK types and are genetically indistinguishable from the corresponding P. vivax strains, suggesting that at least two host transfers have occurred between humans and New World monkeys. We exclude as unlikely the possibility that the two types of sequences could have independently arisen in humans and platyrrhines by natural selection. There are reasons favoring each of the two possible directions of host transfer between humans and monkeys.
Animals↗
Entropy and GC Content in the beta-esterase gene cluster of the Drosophila melanogaster subgroup.
We perform spectral entropy and GC content analyses in the beta-esterase gene cluster, including the Est-6 gene and the psiEst-6 putative pseudogene, in seven species of the Drosophila melanogaster species subgroup. psiEst-6 combines features of functional and nonfunctional genes. The spectral entropies show distinctly lower structural ordering for psiEst-6 than for Est-6 in all species studied. Our observations agree with previous results for D. melanogaster and provide additional support to our hypothesis that after the duplication event Est-6 retained the esterase-coding function and its role during copulation, while psiEst-6 lost that function but now operates in conjunction with Est-6 as an intergene. Entropy accumulation is not a completely random process for either gene. Structural entropy is nucleotide dependent. The relative normalized deviations for structural entropy are higher for G than for C nucleotides. The entropy values are similar for Est-6 and psiEst-6 in the case of A and T but are lower for Est-6 in the case of G and C. The GC content in synonymous positions is uniformly higher in Est-6 than in psiEst-6, which agrees with the reduced GC content generally observed in pseudogenes and nonfunctional sequences. The observed differences in entropy and GC content reflect an evolutionary shift associated with the process of pseudogenization and subsequent functional divergence of psiEst-6 and Est-6 after the duplication event.
Animals↗
Chromosome speciation: humans, Drosophila, and mosquitoes.
Chromosome rearrangements (such as inversions, fusions, and fissions) may play significant roles in the speciation between parapatric (contiguous) or partly sympatric (geographically overlapping) populations. According to the "hybrid-dysfunction" model, speciation occurs because hybrids with heterozygous chromosome rearrangements produce dysfunctional gametes and thus have low reproductive fitness. Natural selection will, therefore, promote mutations that reduce the probability of intercrossing between populations carrying different rearrangements and thus promote their reproductive isolation. This model encounters a disabling difficulty: namely, how to account for the spread in a population of a chromosome rearrangement after it first arises as a mutation in a single individual. The "suppressed-recombination" model of speciation points out that chromosome rearrangements act as a genetic filter between populations. Mutations associated with the rearranged chromosomes cannot flow from one to another population, whereas genetic exchange will freely occur between colinear chromosomes. Mutations adaptive to local conditions will, therefore, accumulate differentially in the protected chromosome regions so that parapatric or partially sympatric populations will genetically differentiate, eventually evolving into different species. The speciation model of suppressed recombination has recently been tested by gene and DNA sequence comparisons between humans and chimpanzees, between Drosophila species, and between species related to Anopheles gambiae, the vector of malignant malaria in Africa.
Animals↗
Systematics and the origin of species: an introduction.
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Animals↗
Is ectopic expression caused by deregulatory mutations or due to gene-regulation leaks with evolutionary potential?
It has long been thought that gene expression is tightly regulated in multicellular eukaryotes, so that expression profiles match functional profiles. This conception emerged from the assumption that gene activity is synonymous with gene function. This paradigm was first challenged by comparative protein electrophoresis studies showing extensive differences in expression patterns among related species. The paradigm is now being challenged by evolutionary transcriptomics using microarray technologies. Most gene expression profiles display features that lack any obvious functional significance. The so-called "ectopic" expression refers to the expression of genes at times and locations where the target gene is not known to have a function. However, ectopic expression might be associated with genuine function even if this function is not essential or has yet to be ascertained. Alternatively, ectopic expression might come about as a superfluous by-product of regulatory systems, which would call for a revision of prevailing ideas about the specificity of gene regulation. We herein review available evidence for ectopic expression and the hypotheses proposed for its origin and evolution. We propose that ectopic expression must be regarded as part of an integrated phenotypic whole. It seems likely that ectopic expression represents a leak in the evolution of regulatory systems, but one that is endowed with considerable evolutionary possibilities.
Animals↗
The emergence and development of genetics in Mexico.
Early in the twentieth century it was shown that Mendel's laws apply to plants and animals and that genes reside on chromosomes. In the 1950s the double-helix model of DNA inaugurated the molecular biology era, which culminated at the end of the century with the publication of the human genome sequence. Although the early response to discoveries in genetics was slow in Mexico, the Green Revolution and other agricultural applications of genetic knowledge contributed greatly to economic welfare, and by the end of the millennium Mexican genetics had reached world-class status at several universities and research institutions.
Animals↗
Theodosius Dobzhansky's role in the emergence and institutionalization of genetics in Mexico.
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Animals↗
The beta-esterase gene cluster of drosophila melanogaster: is psiEst-6 a pseudogene, a functional gene, or both?
Pseudogenes have been defined as non-functional sequences of genomic DNA that are originally derived from functional genes, but exhibit degenerative features such as premature stop codons and frameshifts that prevent their expression. However, there is increasing evidence that pseudogenes are often evolutionarily conserved and may have retained some functional role or acquired new ones. Pseudogenes may exhibit non-functional features as well as functional ones. We investigate, as a model case, the beta-esterase gene cluster of Drosophila melanogaster that includes the Est-6 gene and the psiEst-6 putative pseudogene. We study four samples derived from natural populations of east Africa (Zimbabwe), Europe (Spain), North America (California), and South America (Venezuela). The level of nucleotide diversity is higher in Africa than in the non-African populations. There is twice more nucleotide diversity in psiEst-6 than in Est-6. Linkage disequilibrium within the beta-esterase gene cluster is strong in non-African samples, but much lower in Africa. The population recombination rate is the same for psiEst-6 and Est-6 in Africa, but significantly different in non-African samples. Intragenic gene conversion events are detected within Est-6 and, with much higher incidence, within psiEst-6; intergenic gene conversion events are rare. The extensive intragenic gene conversion within psiEst-6 can be explained by the invasion of retrotransposons that promote a form of homology-dependent gene conversion upon excision. Tests of neutrality with recombination are significant for the beta-esterase gene cluster in the non-African populations but not in Africa. The Est-6 gene sequences exhibit a well-known allozyme dimorphic structure. The sequences of psiEst-6 are also dimorphic in North and South America, but they do not correspond at all (South America) or only imperfectly (North America) to the Est-6 allozyme dimorphism. Sequence dimorphism is less pronounced in the European and African samples. We suggest that demographic history (bottleneck and admixture of genetically differentiated populations) is the major factor shaping the nucleotide pattern in the beta-esterase gene cluster. However, there are some clear indications of positive selection shaping the distribution of nucleotide polymorphism within the cluster. Intergenic epistatic selection may play an important role in the evolution of the beta-esterase gene cluster, preserving psiEst-6 from degenerative destruction and reflecting its functional interaction with Est-6. The Est-6 gene cluster of D. melanogaster represents an example of a functionally interacting complex ('intergene') in which two components (Est-6 and psiEst-6) or more are required to perform the final function.
Animals↗
Nucleotide variation in the tinman and bagpipe homeobox genes of Drosophila melanogaster.
The tinman (tin) and bagpipe (bap) genes are members of the NK homeobox gene family of Drosophila, so that tin occupies a higher position than bap in the regulatory hierarchy. Little is known about the level and pattern of genetic polymorphism in homeobox genes. We have analyzed nucleotide polymorphism in 27 strains of Drosophila melanogaster and one each of D. simulans and D. sechellia, within two closely linked regions encompassing a partial sequence of tin and the complete sequence of bap. The two genes exhibit different levels and patterns of nucleotide diversity. Two sets of sharply divergent sequence types are detected for tin. The haplotype structure of bap is more complex: about half of the sequences are identical (or virtually so), while the rest are fairly heterogeneous. The level of silent nucleotide variability is 0.0063 for tin but significantly higher, 0.0141, for bap, a level of polymorphism comparable to the most polymorphic structural genes of D. melanogaster. Recombination rate and gene conversion are also higher for bap than for tin. There is strong linkage disequilibrium, with the highest values in the introns of both genes and exon II of bap. The patterns of polymorphism in tin and bap are not compatible with an equilibrium model of selective neutrality. We suggest that negative selection and demographic history are the major factors shaping the pattern of nucleotide polymorphism in the tin and bap genes; moreover, there are clear indications of positive selection in the bap gene.
Animals↗
Convergent neofunctionalization by positive Darwinian selection after ancient recurrent duplications of the xanthine dehydrogenase gene.
Gene duplication is a primary source of molecular substrate for the emergence of evolutionary novelties. The chances for redundant gene sequences to evolve new functions are small compared with the probability that the copies become disabled by deleterious mutations. Functional divergence after gene duplication can result in two alternative evolutionary fates: one copy acquires a novel function (neofunctionalization), or each copy adopts part of the tasks of their parental gene (subfunctionalization). The relative prevalence of each outcome is unknown. Similarly unknown is the relative importance of positive selection versus random fixation of neutral mutations. Aldehyde oxidase (Ao) and xanthine dehydrogenase (Xdh) genes encode two complex members of the xanthine oxidase family of molybdo-flavoenzymes that carry different functions. Ao is known to have originated from a duplicate of an Xdh gene in eukaryotes, before the origin of multicellularity. We show that (i) Ao evolved independently twice from two different Xdh paralogs, the second time in the chordates, before the diversification of vertebrates; (ii) after each duplication, the Ao duplicate underwent a period of rapid evolution during which identical sites across the two molecules, involving the flavin adenine dinucleotide and substrate-binding pockets, were subjected to intense positive Darwinian selection; and (iii) the second Ao gene likely endured two periods of redundancy, initially as a duplicate of Xdh and later as a functional equivalent of the old Ao, which is currently absent from the vertebrate genome. Caution is appropriate in structural genomics when using sequence similarity for assigning protein function.
Aldehyde Oxidase↗
Dating the tree of life.
The relative merits of molecular and paleontological dates of major branching points in the tree of life are currently debated. In some cases, molecular date estimates are up to twice as old as paleontological dates. However, although it is true that paleontological dates are often too young (missing fossils), molecular dates are often too old (statistical bias). Intense study of the dating of major splits in the tree of mammals has shown rapprochement as fossil dates become older and molecular dates become younger.
Amino Acid Sequence↗
Genera of the human lineage.
Human fossils dated between 3.5 and nearly 7 million years old discovered during the last 8 years have been assigned to as many as four new genera of the family Hominidae: Ardipithecus, Orrorin, Kenyanthropus, and Sahelanthropus. These specimens are described as having morphological traits that justify placing them in the family Hominidae while creating a new genus for the classification of each. The discovery of these fossils pushed backward by >2 million years the date of the oldest hominids known. Only two or three hominid genera, Australopithecus, Paranthropus, and Homo, had been previously accepted, with Paranthropus considered a subgenus of Australopithecus by some authors. Two questions arise from the classification of the newly discovered fossils: (i) Should each one of these specimens be placed in the family Hominidae? (ii) Are these specimens sufficiently distinct to justify the creation of four new genera? The answers depend, in turn, on the concepts of what is a hominid and how the genus category is defined. These specimens seem to possess a sufficient number of morphological traits to be placed in the Hominidae. However, the nature of the morphological evidence and the adaptation-rooted concept of what a genus is do not justify the establishment of four new genera. We propose a classification that includes four well defined genera: Praeanthropus, Ardipithecus, Australopithecus, and Homo, plus one tentative incertae sedis genus: Sahelanthropus.
Animals↗
A new Drosophila spliceosomal intron position is common in plants.
The 25-year-old debate about the origin of introns between proponents of "introns early" and "introns late" has yielded significant advances, yet important questions remain to be ascertained. One question concerns the density of introns in the last common ancestor of the three multicellular kingdoms. Approaches to this issue thus far have relied on counts of the numbers of identical intron positions across present-day taxa on the assumption that the introns at those sites are orthologous. However, dismissing parallel intron gain for those sites may be unwarranted, because various factors can potentially constrain the site of intron insertion. Demonstrating parallel intron gain is severely handicapped, because intron sequences often evolve exceedingly fast and intron phylogenetic distributions are usually ambiguous, such that alternative loss and gain scenarios cannot be clearly distinguished. We have identified an intron position that was gained independently in animals and plants in the xanthine dehydrogenase gene. The extremely disjointed phylogenetic distribution of the intron argues strongly for separate gain rather than recurrent loss. If the observed phylogenetic pattern had resulted from recurrent loss, all observational support previously gathered for the introns-late theory of intron origins based on the phylogenetic distribution of introns would be invalidated.
Animals↗