Multiple origins of cytologically identical chromosome inversions in the Anopheles gambiae complex.

For more than 60 years, evolutionary cytogeneticists have been using naturally occurring chromosomal inversions to infer phylogenetic histories, especially in insects with polytene chromosomes. The validity of this method is predicated on the assumption that inversions arise only once in the history of a lineage, so that sharing a particular inversion implies shared common ancestry. This assumption of monophyly has been generally validated by independent data. We present the first clear evidence that naturally occurring inversions, identical at the level of light microscopic examination of polytene chromosomes, may not always be monophyletic. The evidence comes from DNA sequence analyses of regions within or very near the breakpoints of an inversion called the 2La that is found in the Anopheles gambiae complex. Two species, A. merus and A. arabiensis, which are fixed for the "same" inversion, do not cluster with each other in a phylogenetic analysis of the DNA sequences within the 2La. Rather, A. merus 2La is most closely related to strains of A. gambiae homozygous for the 2L+. A. gambiae and A. merus are sister taxa, the immediate ancestor was evidently homozygous 2L+, and A. merus became fixed for an inversion cytologically identical to that in A. arabiensis. A. gambiae is polymorphic for 2La/2L+, and the 2La in this species is nearly identical at the DNA level to that in A. arabiensis, consistent with the growing evidence that introgression has or is occurring between these two most important vectors of malaria in the world. The parallel evolution of the "same" inversion may be promoted by the presence of selectively important genes within the breakpoints.     

Acquired inversions in human leucocytes

Peri- and paracentric inversions are observed in human leukocytes at various rates. Four categories are proposed, in relation to the frequency of occurrence, although it may vary with time for a same inversion. Category 1 corresponds to isolated, thus non recurrent inversions. Category 2 (f congruent to .001) corresponds to inv(14)(q12qter) and inv(7)(p14q35) in individuals with presumably normal genetic constitution. Category 3 (f congruent to .01) corresponds to inv(7)(p14q35) in patients affected by ataxia telangiectasia (AT). This inversion, when it is frequent, indicates an abnormal genetic constitution, radiation sensitive and predisposing to cancers. Finally, category 4 (f greater than or equal to .1) corresponds to inversions existing in precancer or in cancer clonal cells: inv(14)(q11.2q32.2) in AT patients affected by a T-cell hemopathy, inv(14)(q12qter) in chronic T-cell lymphocytic leukaemia, and inv(16)(p13q22) in acute myelomonocytic leukaemia with abnormal eosinophils. The prognostic and diagnostic interests of these inversions is discussed.     

Paracentric inversions in human chromosome 7

Summary A paracentric inversion (7)(q11q22) and mosaicism 46,XX/45,X was detected in a female with minor malformations. The same inversion was observed in the mother of the patient. The analysis of high resolution banded chromosmes revealed no visible imbalance in the inverted long arm of the chromosome 7. All published cases of paracentric inversions in the human chromosome 7 are reviewed and the relationship between this inversion and the occurrence of an aneuploidy of the sex chromosomes is discussed.     

Heterogeneity of pericentric inversions of the human y chromosome

Pericentric inversions of the human Y chromosome (inv(Y)) are the result of breakpoints in Yp and Yq. Whether these breakpoints occur recurrently on specific hotspots or appear at different locations along the repeat structure of the human Y chromosome is an open question. Employing FISH for a better definition and refinement of the inversion breakpoints in 9 cases of inv(Y) chromosomes, with seemingly unvarying metacentric appearance after banding analysis, unequivocally resulted in heterogeneity of the pericentric inversions of the human Y chromosome. While in all 9 inv(Y) cases the inversion breakpoints in the short arm fall in a gene-poor region of X-transposed sequences proximal to PAR1 and SRY in Yp11.2, there are clearly 3 different inversion breakpoints in the long arm. Inv(Y)-types I and II are familial cases showing inversion breakpoints that map in Yq11.23 or in Yq11.223, outside the ampliconic fertility gene cluster of DAZ and CDY in AZFc. Inv(Y)-type III shows an inversion breakpoint in Yq11.223 that splits the DAZ and CDY fertility gene-cluster in AZFc. This inversion type is representative of both familial cases and cases with spermatogenetic impairment. In a further familial case of inv(Y), with almost acrocentric morphology, the breakpoints are within the TSPY and RBMY repeat in Yp and within the heterochromatin in Yq. Therefore, the presence of specific inversion breakpoints leading to impaired fertility in certain inv(Y) cases remains an open question.     

Theoretical study of inversions affecting human chromosomes

A theoretical study of inversions affecting human chromosomes is proposed. Taking into consideration the number of bands and the fact that breaks occur at interfaces between bands, it is concluded that: 7.659 different pericentric inversions might be detected in a prometaphasic 802-band karyotype; this number decreases to 917 in a metaphasic 273-band karyotype; 8.607 and 862 different paracentric inversions might be detected in the same karyotypes respectively, but these results are likely to be overestimated. These theoretical data are used for showing that the pericentric inversions detected in human cytogenetic laboratories, are too frequently recurrent and are not distributed at random.     

Radiation induced inversions in human somatic cells

Peri- and paracentric inversions induced by various types of ionizing radiation (gamma and alpha-rays, neutron and neon beams) are analysed. Their frequencies significantly increase for radiation doses greater than or equal to .5 Gy. Their distribution does not seem to be at random. Pericentric are detected 3 to 4 times more frequently than paracentric inversions. Some identical inversions are recurrently induced. A proportion reproduces inversions detected in human cytogenetics laboratories and a larger proportion, chromosomes of other primate species. It seems that breakages, which numbers are roughly proportional to chromosome lengths, lead to reassociations with a limited number of combinations.     

Embryological origins of the human individual

The human fertilized egg is not an embryo, but, more accurately, a conceptus, which contains all the information required to establish both the embryo and extraembryonic supporting tissues. The fertilized eggs of placental mammals, including humans, are entirely dependent upon the female's uterine environment for development to birth. At least half, possibly more, fertilized eggs, or potential lives, do not survive to birth, the greatest loss thought to occur during preimplantation and implantation. Which conceptuses will be lost and which will progress to birth cannot be predicted. The. preimplantation conceptus exhibits extreme developmental lability. Importantly, twinning can occur throughout the preimplantation and implantation phases, and thus, a single human individual has not emerged from the conceptus during this time period. Once the primitive streak is complete during early postimplantation development, identical twinning no longer occurs and the individual emerges. Thus, emergence of the human individual is a process. No single event thus far known is more important than any other prior to formation of the primitive streak. Formation of the streak is a defining moment in the origin of the individual. All further organization of the fetus occurs around this midline. Thus, by 14 days in the human, the body plan for life is established.     

Amplification enhancers and replication origins in the autosomal chorion gene cluster of Drosophila.

Drosophila melanogaster follicle cells over-replicate the chromosomal domain containing the third chromosome chorion gene cluster. Multiple regions of this cluster are needed in cis for attainment of high levels of amplification. We have confirmed the importance of the proposed amplification control element (ACE3) and demonstrated that it can support low levels of follicular amplification in the absence of other elements, but that it lacks detectable activity as a DNA replication origin. We have also demonstrated the existence of additional amplification-enhancing regions (AERs), by analyzing the amplification levels of a series of in situ induced, nested deletions of the chorion cluster. These deletions were induced by P-transposase perturbation of a chorion transposon in a highly amplifying transformed line, and were not accompanied by re-transposition, making possible a quantitative analysis of amplification levels in the absence of chromosomal position effects. Analysis of endogenous replication intermediates in wild-type follicular DNA suggested that at least one of the AERs may be an origin of replication and that amplification uses at least one additional replication origin.     

Primate origins,human origins,and the end of higher taxa

When people learn that I study human evolution and we start talking about it, they sometimes ask me, “How long ago did the first humans live?” My answer is usually another question: “What do you mean by 'humans'?” That response seems as baffling and wrong‐headed to them as their question seems to me, and it usually takes us a while to straighten things out. © 2012 Wiley Periodicals, Inc.     

Reconstructing the origins of human hepatitis viruses

Infections with hepatitis B and C viruses (HBV, HCV) are widespread in human populations throughout the world, and are major causes of chronic liver disease and liver cancer. HBV, HCV and the related hepatitis G virus or GB virus C (referred to here as HGV/GBV-C) are capable of establishing persistent, frequently lifelong infections characterized by high levels of continuous replication. All three viruses show substantial genetic heterogeneity, which has allowed each to be classified into a number of distinct genotypes that have different geographical distributions and associations with different risk groups for infection. Information on their past transmission and epidemiology might be obtained by estimation of the time of divergence of the different genotypes of HCV, HBV and HGV/GBV-C using knowledge of their rates of sequence change. While information on the latter is limited to short observation periods and is therefore subject to considerable error and uncertainty, the relatively recent times of origin for genotype of each virus predicted by this method (HCV, 500-2000 years; HBV, 3000 years; HGV/GBV-C, 200 years) are quite incompatible with their epidemiological distributions in human populations. They also cannot easily be reconciled with the recent evidence for species-associated variants of HBV and HGV/GBV-C in a range of non-human primates. The apparent conservatism of viruses over long periods implied by their epidemiological distributions instead suggests that nucleotide sequence change may be subject to constraints peculiar to viruses with single-stranded genomes, or with overlapping reading frames that defy attempts to reconstruct evolution according to the principles of the 'molecular clock'. Large population sizes and intense selection pressures that optimize fitness may be additional factors that set virus evolution apart from that of their hosts.     

The origins of human cooperation

Bowles and Gintis argue that recent work in behavioural economics shows that humans have other-regarding preferences, i.e., are not purely self-interested. They seek to explain how these preferences may have evolved using a multi-level version of gene-culture coevolutionary theory. In this review essay I critically examine their main arguments.     

Reconstructing human origins in the genomic era

Analyses of recently acquired genomic sequence data are leading to important insights into the early evolution of anatomically modern humans, as well as into the more recent demographic processes that accompanied the global radiation of Homo sapiens. Some of the new results contradict early, but still influential, conclusions that were based on analyses of gene trees from mitochondrial DNA and Y-chromosome sequences. In this review, we discuss the different genetic and statistical methods that are available for studying human population history, and identify the most plausible models of human evolution that can accommodate the contrasting patterns observed at different loci throughout the genome.     

Genetics and modern human origins

The past decade has brought considerable debate on the subject of modern human origins. The nature of the transition from Homo erectus to archaic Homo sapiens to modern H. sapiens has been examined primarily in terms of the relative contribution of archaic populations to later moderns, both within and among geographic regions. The recent African origin model proposes that modern humans appeared first in Africa between 100,000 and 200,000 years ago, and then spread through the rest of the Old World, replacing preexisting populations.^1–6 This model has been referred to by a variety of names, including “replacement”, “Garden of Eden”, “Noah's Ark”, and “out of Africa”. The recent African origin model contrasts with the multiregional model, which proposes a species-wide transition to modern humans throughout the Old World during the past million years or more.^7–10 Indeed, some proponents of the multiregional model advocate placing Homo erectus and all subsequent species of Homo in the evolutionary species Homo sapiens.¹¹ This contrasts with the view that there were multiple hominid species during the Middle Pleistocene. The debate continues.^12,13 Although the multiregional model is often portrayed as proposing a simultaneous transition to anatomically modern humans in different geographic regions, it explicitly allows for varying degrees of continuity across time and space.¹⁰ This model, in the broad sense, does not rule out the possibility that modern human morphology appeared first in Africa and then spread through the rest of the Old World through gene flow. However, not all advocates of the multiregional model adhere to this specific subset of the general model.⁹ Comparison of the African and multiregional models is complicated by considering other, less extreme, hypotheses. Some versions of the recent African origin model imply a speciation event associated with the initial origin of modern humans. Another version, which suggests the possibility of some admixture between “moderns” leaving Africa and preexisting “archaics” elsewhere in the Old World,^14,15 is similar to some variants of the multiregional model, which also suggest that modern morphology appeared first in Africa, but involved admixture with other Old World populations.¹⁶ The major difference between these views appears to be the extent of admixture, although the exact level is never specified. A further complication is the possibility that multiple dispersals from Africa produced a more complicated pattern of worldwide variation.¹⁷     

Gene losses during human origins

Pseudogenization is a widespread phenomenon in genome evolution, and it has been proposed to serve as an engine of evolutionary change, especially during human origins (the “less-is-more” hypothesis). However, there has been no comprehensive analysis of human-specific pseudogenes. Furthermore, it is unclear whether pseudogenization itself can be selectively favored and thus play an active role in human evolution. Here we conduct a comparative genomic analysis and a literature survey to identify 80 nonprocessed pseudogenes that were inactivated in the human lineage after its separation from the chimpanzee lineage. Many functions are involved among these genes, with chemoreception and immune response being outstandingly overrepresented, suggesting potential species-specific features in these aspects of human physiology. To explore the possibility of adaptive pseudogenization, we focus on CASPASE12, a cysteinyl aspartate proteinase participating in inflammatory and innate immune response to endotoxins. We provide population genetic evidence that the nearly complete fixation of a null allele at CASPASE12 has been driven by positive selection, probably because the null allele confers protection from severe sepsis. We estimate that the selective advantage of the null allele is about 0.9% and the pseudogenization started shortly before the out-of-Africa migration of modern humans. Interestingly, two other genes related to sepsis were also pseudogenized in humans, possibly by selection. These adaptive gene losses might have occurred because of changes in our environment or genetic background that altered the threat from or response to sepsis. The identification and analysis of human-specific pseudogenes open the door for understanding the roles of gene losses in human origins, and the demonstration that gene loss itself can be adaptive supports and extends the “less-is-more” hypothesis.     

The archeology of modern human origins

Two competing hypotheses have long dominated specialist thinking on modern human origins. The first posits that modern people emerged in a limited area and spread from there to replace archaic people elsewhere. Proponents of this view currently favor Africa as the modern human birthplace.^1–5 The second suggests that the evolution of modern humans was not geographically restricted, but invlved substantial continuity between archaic and modern populations in all major regions of the occupied world.^6–7 Based solely on the fossil record, both hypotheses are equally defensible, but the spread-and-replationships scenario is far more strongly supported by burgeoning data on the genetic relationships and diversity of living humans.^8–16 These data impy that there was a common ancestor for all living humans in Africa between 280,000 and 140,000 year ago, and that Neanderthals and other archaic humans who inhabited Eurasia during the same interval contributed few, if any, genes to living peiple. I argue here that the spread-and-replacement hypothesis is also more compatible with a third line of evidence: the spread-and-replacement hypothesis is also more compatible with a third line of evidence: the archeological record for human behavioral evolution.